bluuebunny/crossref_metadata_2025 huggingface dataset:
A model for extending antiretroviral care beyond the rural health centre
Authors: Wools‐Kaloustian Kara K , Sidle John E , Selke Henry M , Vedanthan Rajesh , Kemboi Emmanuel K , Boit Lillian J , Jebet Viola T , Carroll Aaron E , Tierney William M , Kimaiyo Sylvester
Published: September 2009

Background

A major obstacle facing many lower‐income countries in establishing and maintaining HIV treatment programmes is the scarcity of trained health care providers. To address this shortage, the World Health Organization has recommend task shifting to HIV‐infected peers.

Methods

We designed a model of HIV care that utilizes HIV‐infected patients, community care coordinators (CCCs), to care for their clinically stable peers with the assistance of preprogrammed personal digital assistants (PDAs). Rather than presenting for the standard of care, monthly clinic visits, in this model, patients were seen every three months in clinics and monthly by their CCCs in the community during the interim two months. This study was conducted in Kosirai Division, western Kenya, where eight of the 24 sub‐locations (defined geographic areas) within the division were randomly assigned to the intervention with the remainder used as controls.

Prior to entering the field, CCCs underwent intensive didactic training and mentoring related to the assessment and support of HIV patients, as well as the use of PDAs. PDAs were programmed with specific questions and to issue alerts if responses fell outside of pre‐established parameters. CCCs were regularly evaluated in six performance areas. An impressionistic analysis on the transcripts from the monthly group meetings that formed the basis of the continuous feedback and quality improvement programme was used to assess this model.

Results

All eight of the assigned CCCs successfully passed their training and mentoring, entered the field and remained active for the two years of the study. On evaluation of the CCCs, 89% of their summary scores were documented as superior during Year 1 and 94% as superior during Year 2. Six themes emerged from the impressionistic analysis in Year 1: confidentiality and “community” disclosure; roles and responsibilities; logistics; clinical care partnership; antiretroviral adherence; and PDA issues. At the end of the trial, of those patients not lost to follow up, 64% (56 of 87) in the intervention and 52% (58 of 103) in the control group were willing to continue in the programme (p = 0.26).

Conclusion

We found that an antiretroviral treatment delivery model that shifted patient monitoring and antiretroviral dispensing tasks into the community by HIV‐infected patients was both acceptable and feasible.

Trial registration

ClinicalTrials.gov ID NCT00371540
Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
Authors: Schwartz Noa , Rubinstein Tamar , Burkly Linda C , Collins Christopher E , Blanco Irene , Su Lihe , Hojaili Bernard , Mackay Meggan , Aranow Cynthia , Stohl William , Rovin Brad H , Michaelson Jennifer S , Putterman Chaim
Published: September 2009

Introduction

TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity.

Methods

Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4.

Results

uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity.

Conclusions

High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN.
Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice
Authors: Simian Marina , Bissell Mina J , Barcellos-Hoff Mary Helen , Shyamala Gopalan
Published: September 2009

Introduction

Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics.

Methods

We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGFβ1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography.

Results

The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGFβ1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice.

Conclusions

These data establish a link between hormonal response, proliferation, modulation of MMP activity and maintenance of basement membrane integrity that depend on a balance in the expression levels of PR-A and PR-B isoforms. Notably, concomitant increased proliferation, due to inhibition of TGFβ1 activation, and loss of basement membrane integrity, via increased MMP-2 activity, appear to be prerequisites for the PR-A hyperplastic phenotype.
Candidemia on presentation to the hospital: development and validation of a risk score
Authors: Shorr Andrew F , Tabak Ying P , Johannes Richard S , Sun Xiaowu , Spalding James , Kollef Marin H
Published: September 2009

Introduction

Candidemia results in substantial morbidity and mortality, especially if initial antifungal therapy is delayed or is inappropriate; however, candidemia is difficult to diagnose because of its nonspecific presentation.

Methods

To develop a risk score for identifying hospitalized patients with candidemia, we performed a retrospective analysis of a large database of 176 acute-care hospitals in the United States. We studied 64,019 patients with bloodstream infection (BSI) on presentation from 2000 through 2005 (derivation cohort) and 24,685 from 2006 to 2007 (validation cohort). We used recursive partitioning (RPART) to identify the best discriminators for Candida as the cause of BSI. We compared three sets of models (equal-weight, unequal-weight, vs full model with additional variables from logistic regression model) for sensitivity analysis.

Results

The RPART identified 6 variables as the best discriminators: age < 65 years, temperature ≤ 98°F or severe altered mental status, cachexia, previous hospitalization within 30 days, admitted from other healthcare facility, and need for mechanical ventilation. The prevalence for patients presented with 0 through 6 risk factors in the derivation cohort was 28.7%, 38.8%, 21.8%, 8.3%, 2.1%, 0.3%, and < 0.1% respectively. The corresponding candidemia rates were 0.4% (69/18,355), 0.8% (196/24,811), 1.6% (229/13,984), 3.2% (168/5,330), 4.2% (58/1,371), 9.6% (15/157), and 27.3% (3/11) respectively (P < 0.0001). Findings were similar in the validation cohort (P < 0.0001). The equal-weight risk score model, which signed 1 point to each risk factor, yielded good discrimination in both cohorts with areas under the receiver operating curve (AUROCs) of 0.70 versus 0.71 (derivation versus validation). AUROC values were similar for the unequal-weight model, which signed different weight to each risk factor based on multivariable logistic regression coefficient, (AUROCs, 0.70-0.72). Both equal-weight and unequal-weight models were well calibrated (all Hosmer-Lemshow P > 0.10, indicating predicted and observed candidemia rates did not differ significant across the 7 risk stratus). The full model with 16 risk factors had slightly higher AUROCs (0.74 versus 0.73 for derivation versus validation); however, 7 variables were no longer significant in the recalibrated model for the validation cohort, indicating that the additional items did not materially enhance the model.

Conclusions

A simple equal-weight risk score differentiated patients' risk for candidemia in a graded fashion upon hospital presentation.
Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2–Positive, Hormone Receptor–Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study
Authors: Kaufman Bella , Mackey John R. , Clemens Michael R. , Bapsy Poonamalle P. , Vaid Ashok , Wardley Andrew , Tjulandin Sergei , Jahn Michaela , Lehle Michaela , Feyereislova Andrea , Révil Cédric , Jones Alison
Published: September 2009

Purpose

TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor–copositive metastatic breast cancer (MBC).

Patients and Methods

Postmenopausal women with HER2/hormone receptor–copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population.

Results

Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor–positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure.

Conclusion

Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor–copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.
Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma
Authors: Richardson Paul G. , Weller Edie , Jagannath Sundar , Avigan David E. , Alsina Melissa , Schlossman Robert L. , Mazumder Amitabha , Munshi Nikhil C. , Ghobrial Irene M. , Doss Deborah , Warren Diane L. , Lunde Laura E. , McKenney Mary , Delaney Carol , Mitsiades Constantine S. , Hideshima Teru , Dalton William , Knight Robert , Esseltine Dixie-Lee , Anderson Kenneth C.
Published: September 2009

Purpose

Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM.

Patients and Methods

Patients received lenalidomide 5, 10, or 15 mg/d on days 1 through 14 and received bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20mg or 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) was added for progressive disease after two cycles. Primary end points were safety and MTD determination.

Results

Thirty-eight patients were enrolled across six dose cohorts. The MTD was lenalidomide 15 mg/d plus bortezomib 1.0 mg/m2. Dose-limiting toxicities (n = 1 for each) were grade 3 hyponatremia and herpes zoster reactivation and grade 4 neutropenia. The most common treatment-related, grades 3 to 4 toxicities included reversible neutropenia, thrombocytopenia, anemia, and leukopenia. Among 36 response-evaluable patients, 61% (90% CI, 46% to 75%) achieved minimal response or better. Among 18 patients who had dexamethasone added, 83% (90% CI, 62% to 95%) achieved stable disease or better. Median overall survival was 37 months.

Conclusion

Lenalidomide plus bortezomib was well tolerated and showed promising activity with durable responses in patients with relapsed and relapsed/refractory MM, including patients previously treated with lenalidomide, bortezomib, and/or thalidomide. The combination of lenalidomide, bortezomib, and dexamethasone is being investigated in a phase II study in this setting and in newly diagnosed MM.
Survival After Second Primary Neoplasms of the Brain or Spinal Cord in Survivors of Childhood Cancer: Results From the British Childhood Cancer Survivor Study
Authors: Taylor Aliki J. , Frobisher Clare , Ellison David W. , Reulen Raoul C. , Winter David L. , Taylor Roger E. , Stiller Charles A. , Lancashire Emma R. , Tudor Edward C.G. , Baggott Christina , May Shaun , Hawkins Mike M.
Published: September 2009

Purpose

Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade, treatment and pretreatment factors, and location and size of tumor. We carried out a study to investigate survival and factors affecting survival of all diagnostic types of second primary brain or spinal cord neoplasms.

Patients and Methods

The British Childhood Cancer Survivor Study (BCCSS) is a long-term population-based follow-up study of 17,980 5-year survivors of childhood cancer. We used relative survival and multivariate Cox regression analysis to determine 5-year relative survival and factors affecting survival in second primary meningiomas and gliomas that developed in survivors included in the BCCSS.

Results

There were 247 second primary brain or spinal cord neoplasms, including 137 meningiomas and 73 gliomas in a young adult population. Five-year relative survival after meningiomas was similar for males (84.0%; 95% CI, 72.6% to 91.1%) and females (81.7%; 95% CI, 69.9% to 89.3%). For gliomas, 5-year relative survival was 19.5% (95% CI, 8.6% to 33.7%) for males and females. Multivariate analysis showed significant heterogeneity by decade of treatment (P = .04), grade (P = .03), and genetic risk (P = .03) for rate of mortality after a meningioma. For gliomas, survival was significantly affected by grade (P < .001).

Conclusion

Our results indicate survival is poor after second primary glioma in this young adult population, although survival after second primary meningioma is good. Our study has clinical implications for the surveillance of childhood cancer survivors at risk of developing second primary brain tumors, in particular survivors of childhood acute lymphoblastic leukemia or childhood brain tumors.
To Tell or Not to Tell: The Community Wants to Know About Expensive Anticancer Drugs As a Potential Treatment Option
Authors: Mileshkin Linda , Schofield Penelope E. , Jefford Michael , Agalianos Emilia , Levine Michele , Herschtal Alan , Savulescu Julian , Thomson Jacqui Ann , Zalcberg John R.
Published: September 2009

Purpose

Many new cancer treatments are available only at significant financial cost to the patient. We previously reported that Australian medical oncologists commonly do not discuss unsubsidized, expensive anticancer drugs (EACD) because of concern about causing distress. We argued that this position was not consistent with modern ethical principals but wanted to seek the community viewpoint.

Methods

A cross-sectional telephone survey of the Australian general public was performed. Respondents' views were sought about three hypothetical scenarios in which they were diagnosed with incurable cancer and an EACD treatment (out-of-pocket cost US$25,000) was available.

Results

Responses were obtained from 1,255 respondents (response rate, 43%). One hundred thirty-seven (11%) had a prior cancer diagnosis. Ninety-one percent of respondents wanted to be told by their doctor about an EACD that could improve survival by an additional 4 to 6 months, with 51% prepared to pay for it. People were more willing to pay if the drug could improve quality of life (71%) or if there was no effective standard treatment (76%). Sixty-eight percent believed the government should pay. Cost would be a significant financial burden for 31% of those willing to pay. Those more likely to want to be informed were younger, employed, better-educated, or had higher income levels (P < .05). Responses did not vary with the person's personal experience of cancer. Of the 9% who did not wish to be informed, half of these were concerned about the information causing distress.

Conclusion

The Australian general public wants to be informed about EACD as potential treatment options, even if they are not willing or readily able to pay for them.
Lapatinib Combined With Letrozole Versus Letrozole and Placebo As First-Line Therapy for Postmenopausal Hormone Receptor–Positive Metastatic Breast Cancer
Authors: Johnston Stephen , Pippen John , Pivot Xavier , Lichinitser Mikhail , Sadeghi Saeed , Dieras Veronique , Gomez Henry Leonidas , Romieu Gilles , Manikhas Alexey , Kennedy M. John , Press Michael F. , Maltzman Julie , Florance Allison , O'Rourke Lisa , Oliva Cristina , Stein Steven , Pegram Mark
Published: September 2009

Purpose

Cross-talk between human epidermal growth factor receptors and hormone receptor pathways may cause endocrine resistance in breast cancer. This trial evaluated the effect of adding lapatinib, a dual tyrosine kinase inhibitor blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2), to the aromatase inhibitor letrozole as first-line treatment of hormone receptor (HR) –positive metastatic breast cancer (MBC).

Patients and Methods

Postmenopausal women with HR-positive MBC were randomly assigned to daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally) or letrozole and placebo. The primary end point was progression-free survival (PFS) in the HER2-positive population.

Results

In HR-positive, HER2-positive patients (n = 219), addition of lapatinib to letrozole significantly reduced the risk of disease progression versus letrozole-placebo (hazard ratio [HR] = 0.71; 95% CI, 0.53 to 0.96; P = .019); median PFS was 8.2 v 3.0 months, respectively. Clinical benefit (responsive or stable disease ≥ 6 months) was significantly greater for lapatinib-letrozole versus letrozole-placebo (48% v 29%, respectively; odds ratio [OR] = 0.4; 95% CI, 0.2 to 0.8; P = .003). Patients with centrally confirmed HR-positive, HER2-negative tumors (n = 952) had no improvement in PFS. A preplanned Cox regression analysis identified prior antiestrogen therapy as a significant factor in the HER2-negative population; a nonsignificant trend toward prolonged PFS for lapatinib-letrozole was seen in patients who experienced relapse less than 6 months since prior tamoxifen discontinuation (HR = 0.78; 95% CI, 0.57 to 1.07; P = .117). Grade 3 or 4 adverse events were more common in the lapatinib-letrozole arm versus letrozole-placebo arm (diarrhea, 10% v 1%; rash, 1% v 0%, respectively), but they were manageable.

Conclusion

This trial demonstrated that a combined targeted strategy with letrozole and lapatinib significantly enhances PFS and clinical benefit rates in patients with MBC that coexpresses HR and HER2.
American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards
Authors: Jacobson Joseph O. , Polovich Martha , McNiff Kristen K. , LeFebvre Kristine B. , Cummings Charmaine , Galioto Michele , Bonelli Katherine R. , McCorkle Michele R.
Published: September 2009

Standardization of care can reduce the risk of errors, increase efficiency, and provide a framework for best practice. In 2008, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) invited a broad range of stakeholders to create a set of standards for the administration of chemotherapy to adult patients in the outpatient setting. At the close of a full-day structured workshop, 64 draft standards were proposed. After a formal process of electronic voting and conference calls, 29 draft standards were eliminated, resulting in a final list of 35 draft measures. The proposed set of standards was posted for 6 weeks of open public comment. Three hundred twenty-two comments were reviewed by the Steering Group and used as the basis for final editing to a final set of standards. The final list includes 31 standards encompassing seven domains, which include the following: review of clinical information and selection of a treatment regimen; treatment planning and informed consent; ordering of treatment; drug preparation; assessment of treatment compliance; administration and monitoring; and assessment of response and toxicity monitoring. Adherence to ASCO and ONS standards for safe chemotherapy administration should be a goal of all providers of adult cancer care.
Cost Structure, Customer Profitability, and Retention Implications of Self-Service Distribution Channels: Evidence from Customer Behavior in an Online Banking Channel
Authors: Campbell Dennis , Frei Frances
Published: September 2009

This paper uses the context of online banking to investigate the consequences of using self-service distribution channels to alter customer interactions with the firm. Using a sample of retail banking customers observed over a 30-month period at a large U.S. bank, we test whether changes in service consumption, cost to serve, and customer profitability are associated with the adoption of online banking. We find that customer adoption of online banking is associated with (1) substitution, primarily from incrementally more costly self-service delivery channels (automated teller machine and voice response unit); (2) augmentation of service consumption in more costly service delivery channels (branch and call center); (3) a substantial increase in total transaction volume; (4) an increase in estimated average cost to serve resulting from the combination of points (1)–(3); and (5) a reduction in short-term customer profitability. However, we find that use of the online banking channel is associated with higher customer retention rates over one-, two-, and three-year horizons. The documented relationship between the use of online banking and customer retention remains positive even after controlling for self-selection into the online channel. We also find evidence that future market shares for our sample firm are systematically higher in markets with high contemporaneous utilization rates for the online banking channel. This finding holds even after controlling for contemporaneous market share, suggesting it is not simply the result of increased market power leading to the acquisition of online banking customers.
The Duration of Patent Examination at the European Patent Office
Authors: Harhoff Dietmar , Wagner Stefan
Published: September 2009

We analyze the duration and outcomes of patent examination at the European Patent Office utilizing an unusually rich data set covering a random sample of 215,265 applications filed between 1982 and 1998. In our empirical analysis, we distinguish between three groups of determinants: applicant characteristics, indicators of patent quality and value, and determinants that affect the complexity of the examination task. The results from an accelerated failure time model indicate that more controversial claims lead to slower grants but faster withdrawals, whereas well-documented applications are approved faster and withdrawn more slowly. We find strong evidence that applicants accelerate grant proceedings for their most valuable patents, but that they also prolong the battle for such patents if a withdrawal or refusal is imminent. This paper develops implications of these results for managerial decision making in research and development and innovation management.
Detailing vs. Direct-to-Consumer Advertising in the Prescription Pharmaceutical Industry
Authors: Bala Ram , Bhardwaj Pradeep
Published: September 2009

The pharmaceutical industry has always used sales representatives to target physicians (detailing), who are a key link in sales and market share for prescription pharmaceuticals. Since August of 1997, when the Food and Drug Administration eased the restrictions on direct-to-consumer advertising (DTCA), there has been a dramatic increase in the use of DTCA by pharmaceutical firms to target end customers (patients). DTCA seems to have two different effects on pharmaceutical markets. The first is to inform patients about the availability of drugs for some ailments, thus expanding the market (constructive). The second is to persuade patients to talk about specific brands when they meet physicians, with the objective of influencing market share (combative). We consider both effects of DTCA in the presence of a detailing program in a competitive environment. We incorporate the dynamics of physician-patient interaction in a game-theoretic model where firms decide on the form of DTCA to adopt (constructive or combative) and then compete in the marketplace by choosing detailing and DTCA levels. We answer four questions: What is the impact of adopting DTCA on competitive intensity? How do optimal detailing levels for a firm change with the adoption of DTCA? How should the DTCA strategy for a firm vary depending on whether it is stronger or weaker in its degree of influence in the physician's office? Finally, under what conditions would competing firms voluntarily decide to pursue constructive DTCA?
Social Capital for Hire? Mobility of Technical Professionals and Firm Influence in Wireless Standards Committees
Authors: Dokko Gina , Rosenkopf Lori
Published: September 2009

The movement of personnel between firms has been shown to have important implications for firms, yet there has been little direct investigation of the underlying mechanisms. We propose that in addition to their human capital, mobile individuals carry social capital, affecting the outcomes of the firms they join and leave by altering the patterns of interaction between firms. In this study, we examine how job mobility affects firm influence in a technical standards setting committee for U.S. wireless telecommunications. We hypothesize and find that hiring individuals who are richer in social capital increases firm influence in technical standards setting committees by increasing the hiring firm's social capital. We also find the benefits of hiring social capital are attenuated when an interfirm relationship is maintained by multiple individuals. In contrast, we find that the loss of personnel does not affect a firm's social capital or influence over standards directly but that it does have an effect on firm social capital and influence contingent on changes in the firm's business strategy. In advancing these arguments, we address the broader question of individuals as carriers of social capital and the conditions under which interpersonal connections are appropriable by firms.
Experiencing the Improbable: Rare Events and Organizational Learning
Authors: Lampel Joseph , Shamsie Jamal , Shapira Zur
Published: September 2009

Organizations that go through rare and unusual events, whether they are costly or beneficial, face the challenge of interpreting and learning from these experiences. Although research suggests that organizations respond to this challenge in a variety of ways, we lack a framework for comparing and analyzing how organizational learning is affected by rare events. This paper develops such a framework. We begin by first outlining two views of rare events. The first view defines rare events as probability estimates, usually calculated from the frequency of the event. The second view defines rare events as opportunities for unique sensemaking based on the enacted salience of specific features of the rare events. We next use these definitions to explore how rare events trigger learning, and then examine the kind of learning processes that are triggered by rare events. We conclude with a discussion of promising areas of research on learning from rare events.
Anti-human Vascular Endothelial Growth Factor (VEGF) Antibody Selection for Immunohistochemical Staining of Proliferating Blood Vessels
Authors: van der Loos Chris M. , Meijer-Jorna Lorine B. , Broekmans Marloes E.C. , Ploegmakers Hanneke P.H.M. , Teeling Peter , de Boer Onno J. , van der Wal Allard C.
Published: September 2009

Nine commercially available vascular endothelial growth factor (VEGF) antibodies were investigated for their ability to immunostain vascular malformations (VMs) with or without immature capillary proliferation. First, all antibodies were optimized for their performance in IHC, with placenta and colon adenocarcinoma as positive control tissues. Five antibodies were regarded as unfit for VEGF immunostaining based on poor immunostaining criteria. Subsequently, Western blot analysis using VEGF rabbit polyclonal antibody (Thermo RB-9031) revealed a clear 45-kDa band in tissue extracts from VMs with immature capillary proliferation and a high Ki67-labeling index, whereas tissue extracts from mature VMs without microvascular proliferation and no Ki67-labeling index demonstrated only a very weak 45-kDa band. In contrast, two VEGF antibodies, including the popular Santa Cruz A-20, revealed bands at 45 kDa of similar intensity in tissue extracts from both types of VMs. Staining characteristics of the 45-kDa band were reflected in the results obtained in IHC.
A Comparison of the Performance of Environmentally Friendly Anhydrous Fire Resistant Hydraulic Fluids
Authors: Greaves Martin R. , Knoell Jim C.
Published: September 2009

Many industries benefit from using fire resistant hydraulic fluids including aviation, steel processing, aluminum die-casting, marine, mining, and many more. In recent years, environmental performance has become an increasingly important feature of hydraulic fluids notably in Europe with the introduction of the European Eco-Label and in the United States with the recommendations provided by the 2002 U.S. Farm Bill for procurement of bio-based materials by Federal agencies. Environmental performance favors esters and vegetable oils as the preferred technologies today but polyalkylene glycols (PAGs) offer an alternative option although they are not derived from renewable sources. The performance of several environmentally friendly fire resistant anhydrous hydraulic fluids based on these technologies has been evaluated in laboratory bench tests. All fluids exhibit excellent hydraulic vane pump wear performance. In high temperature oxidation studies, synthetic products based on esters and PAGs, out-perform vegetable oils. Hydrolytic stability results show hydrolysis of synthetic esters and vegetable oils occurs to form acids in contrast to a PAG formulation, which is more stable. Furthermore the unique water solubility and non-sheening aspects of the PAG product indicate it may be a more favorable choice for use in applications where fluid leakage into water-ways is a concern. By understanding the performance of each product technology, direction can be provided in the type of equipment and industries where these fluids can be used and a discussion pertaining to this is presented herein.
Case Depth and Static Capacity of Surface Induction-Hardened Rings
Authors: Lai Junbiao , Ovize Pascal , Kuijpers Hans , Bacchettto Andrea , Ioannides Stathis
Published: September 2009

Large-size slewing bearings are usually surface hardened by means of induction heating. The load-carrying capacity of the bearing is dependent on, among others, the depth of the hardened layer, i.e., case depth (CD). It is of crucial importance for bearing manufacturers to ensure that sufficient CD is produced to meet the required bearing capacity for the applications. Compared to through-hardened bearings, the calculation method for the load-carrying capacity of surface-hardened bearings, especially the induction-hardened bearings, is not well established. This paper reports on a new calculation method for the static capacity of induction-hardened rings. The method is based on consideration of both the plastic indentation on the raceway and the damage tolerance in the subsurface region. The models for evaluating plastic indentation and subsurface damage have been validated with the standing contact fatigue testing.
Blurring the Boundaries: Tan Dun's Tinte and The First Emperor
Authors: Sheppard W. Anthony
Published: September 2009

Tan Dun's 2006 opera The First Emperor dramatically transgresses stylistic, cultural, genre, and aesthetic boundaries and prompts investigation of critical methods and categories. This opera's multiplicity and engagement with the operatic past brings into focus relationships between Chinese, European, and experimental American operatic traditions and Romantic, modernist, and postmodernist modes of Orientalist representation. Powers's study of Puccini's manipulation of multiple styles in Turandot is a model for tracing Tan's stylistic sources and exploring their interaction in The First Emperor. Tan's use of conventions from the Orientalist operatic tradition and treatment of thematic material indicates an attempt to accommodate audience expectations. Other recent operas influenced by Chinese operatic traditions and the recent reception of Chinese opera in the West likely shaped Tan's composition and offer useful contextual and comparative perspectives. The critical reception and revision of this high-profile opera raise issues central to the creation of contemporary opera.
Brahms's “Sinfonie-Serenade” and the Politics of Genre
Authors: Vaillancourt Michael
Published: September 2009

Brahms's First Serenade, op. 11, has played a relatively minor role in scholarly accounts of Brahms's stylistic development, which often depict the work as a tentative step toward the composer's “first maturity” or as one of several failed attempts to create a symphony. By contrast, the earliest reviewers of the Serenade heard the piece as a crucial turning point in his career, and they interpreted his choice of genre as a bold statement in the emerging debate on the future course of German music. In this view, the genre of the orchestral serenade forged a link with an idealized Viennese classicism, thereby representing a denial of the ideals of Franz Brendel's “New German” school.

By reading Brahms's Serenade in terms of genre, we can begin to assess the qualities that informed its contemporary reception. Approaching genre as an interpretive mode allows us to understand the composer's provocative juxtaposition of numerous topics of discourse—the symphonic, the pastoral, the sublime, as well as the reinterpretation of specific classical gestures—as a key to the musical meaning of the piece. Brahms's extensive references to music by Mozart, Haydn, and Beethoven go beyond simple allusion to embrace the reinterpretation of compositional techniques that situate the piece within the tradition of instrumental Nachtmusik. Heard through genre, the Serenade thus emerges as a pointed response to mid nineteenth-century theories of radical modernism.
Angiogenesis and vascular function in the ovary
Authors: Robinson R S , Woad K J , Hammond A J , Laird M , Hunter M G , Mann G E
Published: September 2009

Ovarian function is dependent on the establishment and continual remodelling of a complex vascular system. This enables the follicle and/or corpus luteum (CL) to receive the required supply of nutrients, oxygen and hormonal support as well as facilitating the release of steroids. Moreover, the inhibition of angiogenesis results in the attenuation of follicular growth, disruption of ovulation and drastic effects on the development and function of the CL. It appears that the production and action of vascular endothelial growth factor A (VEGFA) is necessary at all these stages of development. However, the expression of fibroblast growth factor 2 (FGF2) in the cow is more dynamic than that of VEGFA with a dramatic upregulation during the follicular–luteal transition. This upregulation is then likely to initiate intense angiogenesis in the presence of high VEGFA levels. Recently, we have developed a novel ovarian physiological angiogenesis culture system in which highly organised and intricate endothelial cell networks are formed. This system will enable us to elucidate the complex inter-play between FGF2 and VEGFA as well as other angiogenic factors in the regulation of luteal angiogenesis. Furthermore, recent evidence indicates that pericytes might play an active role in driving angiogenesis and highlights the importance of pericyte–endothelial interactions in this process. Finally, the targeted promotion of angiogenesis may lead to the development of novel strategies to alleviate luteal inadequacy and infertility.
Simulating the Yield Impacts of Organ-Level Quantitative Trait Loci Associated With Drought Response in Maize: A “Gene-to-Phenotype” Modeling Approach
Authors: Chenu Karine , Chapman Scott C , Tardieu François , McLean Greg , Welcker Claude , Hammer Graeme L
Published: September 2009

Under drought, substantial genotype–environment (G × E) interactions impede breeding progress for yield. Identifying genetic controls associated with yield response is confounded by poor genetic correlations across testing environments. Part of this problem is related to our inability to account for the interplay of genetic controls, physiological traits, and environmental conditions throughout the crop cycle. We propose a modeling approach to bridge this “gene-to-phenotype” gap. For maize under drought, we simulated the impact of quantitative trait loci (QTL) controlling two key processes (leaf and silk elongation) that influence crop growth, water use, and grain yield. Substantial G × E interaction for yield was simulated for hypothetical recombinant inbred lines (RILs) across different seasonal patterns of drought. QTL that accelerated leaf elongation caused an increase in crop leaf area and yield in well-watered or preflowering water deficit conditions, but a reduction in yield under terminal stresses (as such “leafy” genotypes prematurely exhausted the water supply). The QTL impact on yield was substantially enhanced by including pleiotropic effects of these QTL on silk elongation and on consequent grain set. The simulations obtained illustrated the difficulty of interpreting the genetic control of yield for genotypes influenced only by the additive effects of QTL associated with leaf and silk growth. The results highlight the potential of integrative simulation modeling for gene-to-phenotype prediction and for exploiting G × E interactions for complex traits such as drought tolerance.
Racial differences in the association between body mass index and serum IGF1, IGF2, and IGFBP3
Authors: Fowke Jay H , Matthews Charles E , Yu Herbert , Cai Qiuyin , Cohen Sarah , Buchowski Maciej S , Zheng Wei , Blot William J
Published: September 2009

African–American (AA) race/ethnicity, lower body mass index (BMI), and higher IGF1 levels are associated with premenopausal breast cancer risk. This cross-sectional analysis investigated whether BMI or BMI at age 21 years contributes to racial differences in IGF1, IGF2, IGF-binding protein 3 (IGFBP3), or free IGF1. Participants included 816 white and 821 AA women between ages 40 and 79 years across a wide BMI range (18.5–40 kg/m2). Compared with white women, AA women had higher mean IGF1 (146.3 vs 134.4 ng/ml) and free IGF1 (0.145 vs 0.127) levels, and lower IGF2 (1633.0 vs 1769.3 ng/ml) and IGFBP3 (3663.3 vs 3842.5 ng/ml) levels (all P<0.01; adjusted for age, height, BMI, BMI at age 21 years, and menopausal status). Regardless of race, IGF1 and free IGF1 levels rose sharply as BMI increased to 22–24 kg/m2, and then declined thereafter, while IGF2 and IGFBP3 levels tended to rise with BMI. In contrast, BMI at age 21 years was inversely associated with all IGF levels, but only among white women (P-interaction=0.01). With the decline in IGF1 with BMI at age 21 years among whites, racial differences in IGF1 significantly increased among women who were obese in early adulthood. In summary, BMI was associated with IGF1 levels regardless of race/ethnicity, while obesity during childhood or young adulthood may have a greater impact on IGF1 levels among white women. The effects of obesity throughout life on the IGF axis and racial differences in breast cancer risk require study.
Interannual variation of carbon fluxes from three contrasting evergreen forests: the role of forest dynamics and climate
Authors: Sierra Carlos A. , Loescher Henry W. , Harmon Mark E. , Richardson Andrew D. , Hollinger David Y. , Perakis Steven S.
Published: September 2009

Interannual variation of carbon fluxes can be attributed to a number of biotic and abiotic controls that operate at different spatial and temporal scales. Type and frequency of disturbance, forest dynamics, and climate regimes are important sources of variability. Assessing the variability of carbon fluxes from these specific sources can enhance the interpretation of past and current observations. Being able to separate the variability caused by forest dynamics from that induced by climate will also give us the ability to determine if the current observed carbon fluxes are within an expected range or whether the ecosystem is undergoing unexpected change. Sources of interannual variation in ecosystem carbon fluxes from three evergreen ecosystems, a tropical, a temperate coniferous, and a boreal forest, were explored using the simulation model STANDCARB. We identified key processes that introduced variation in annual fluxes, but their relative importance differed among the ecosystems studied. In the tropical site, intrinsic forest dynamics contributed ∼30% of the total variation in annual carbon fluxes. In the temperate and boreal sites, where many forest processes occur over longer temporal scales than those at the tropical site, climate controlled more of the variation among annual fluxes. These results suggest that climate‐related variability affects the rates of carbon exchange differently among sites. Simulations in which temperature, precipitation, and radiation varied from year to year (based on historical records of climate variation) had less net carbon stores than simulations in which these variables were held constant (based on historical records of monthly average climate), a result caused by the functional relationship between temperature and respiration. This suggests that, under a more variable temperature regime, large respiratory pulses may become more frequent and high enough to cause a reduction in ecosystem carbon stores. Our results also show that the variation of annual carbon fluxes poses an important challenge in our ability to determine whether an ecosystem is a source, a sink, or is neutral in regard to CO2 at longer timescales. In simulations where climate change negatively affected ecosystem carbon stores, there was a 20% chance of committing Type II error, even with 20 years of sequential data.
A jack‐of‐all‐trades and still a master of some: prevalence and host range in avian malaria and related blood parasites
Authors: Hellgren Olof , Pérez-Tris Javier , Bensch Staffan
Published: September 2009

A parasite's ability to be a specialist vs. a generalist may have consequences for its prevalence within one or more if its host species. In this study we investigated the relationship between host specialization and prevalence in the highly species diverse avian blood parasites of the genera Plasmodium and Haemoproteus. Contrary to trade‐off hypotheses that may explain host specialization, within both genera the parasites with the ability to complete their life cycles and be transmitted across a wide host range (broad compatibility) were also the most common parasites within their compatible host species. These patterns remained unchanged when the host species with the highest prevalence were excluded, which reduces the possibility that the observed pattern was caused by parasites reaching high prevalence in a single main host, and being “spilled over” to other host species. We hypothesize that a positive relationship between parasite host range and prevalence might be explained by an overall higher encounter rate for the parasites with broad host range, which compensates for possibly reduced performance of parasites in each host species. Overall, these results show that parasites with the ability to successfully infect a wide variety of host species of broad ancestry also can have the ability to be the most prevalent in single host species.