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Ellen Childs,1,* Christy D Remein,2,* Robina M Bhasin,3 Angelique C Harris,4 Alyssa Day,4 Lisa M Sullivan,5 David L Coleman,4 Emelia J Benjamin4,6 1Division of Health and Environment, Abt Associates, Rockville, MD, USA; 2Institute of Spirituality and Health, George Washington University, School of Medicine and Health Sciences, Washington, DC, USA; 3Penn Foster Education Group, Boston, MA, USA; 4Department of Medicine, Boston University School of Medicine, Boston, MA, USA; 5Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; 6Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Christy D RemeinInstitute of Spirituality and Health, George Washington University School of Medicine and Health Sciences, 2600 Virginia Avenue, NW – Room 342, Washington, Washington, 20037, USATel +12029943549Email cdremein@email.gwu.eduPurpose: Drawing on the decade of experience of Boston University Medical Campus’ Faculty Development Office, this paper reports strategies used to launch and continually improve faculty development programming within an academic health sciences campus.Patients and Methods: The authors explain the steps that Boston University Medical Campus took to institute their set of faculty development programs, including an overview of resources on how to periodically conduct needs assessments, engage key institutional stakeholders, design and evaluate an array of programming to meet the needs of a diverse faculty, and institute real-time program modifications.Results: In a step-by-step guide, and by highlighting vital lessons learned, the authors describe a process by which biomedical educators can create and sustain a robust faculty development office within their own institutions.Conclusion: This paper identifies steps to launch and improve faculty development program. Faculty development programs should be expanded to support faculty in academic medical centers.Keywords: faculty development, career development, mentoring, medical education

The first step in stamping out litigation fever is creating a corporate environment in which discriminatory practices cannot survive. [ABSTRACT FROM AUTHOR]

Enacted in the pre-managed care days, ERISA has shielded health plans from liability in a way the nation's lawmakers may never have intended. The business community watches warily as this blanket protection erodes. [ABSTRACT FROM AUTHOR]

The second in our series of site reviews highlights organizations -- and the wealth of health policy and benefits information they provide on the World Wide Web. [ABSTRACT FROM AUTHOR]

Abstract: The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Introduction: Traumatic brain injury (TBI) is a leading cause of disability in the US. Angiotensin 1-7 (Ang-1-7), an endogenous peptide, acts at the G protein coupled MAS1 receptors (MASR) to inhibit inflammatory mediators and decrease reactive oxygen species within the CNS. Few studies have identified whether Ang-(1-7) decreases cognitive impairment following closed TBI. This study examined the therapeutic effect of Ang-(1-7) on secondary injury observed in a murine model of mild TBI (mTBI) in a closed skull, single injury model., Materials and Methods: Male mice ( n = 108) underwent a closed skull, controlled cortical impact injury. Two hours after injury, mice were administered either Ang-(1-7) ( n = 12) or vehicle ( n = 12), continuing through day 5 post-TBI, and tested for cognitive impairment on days 1-5 and 18. pTau, Tau, GFAP, and serum cytokines were measured at multiple time points. Animals were observed daily for cognition and motor coordination via novel object recognition. Brain sections were stained and evaluated for neuronal injury., Results: Administration of Ang-(1-7) daily for 5 days post-mTBI significantly increased cognitive function as compared to saline control-treated animals. Cortical and hippocampal structures showed less damage in the presence of Ang-(1-7), while Ang-(1-7) administration significantly changed the expression of pTau and GFAP in cortical and hippocampal regions as compared to control., Discussion: These are among the first studies to demonstrate that sustained administration of Ang-(1-7) following a closed-skull, single impact mTBI significantly improves neurologic outcomes, potentially offering a novel therapeutic modality for the prevention of long-term CNS impairment following such injuries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bruhns, Sulaiman, Gaub, Bae, Davidson Knapp, Larson, Smith, Coleman, Staatz, Sandweiss, Joseph, Hay, Largent-Milnes and Vanderah.)

Dennis Lindberg came into his aunt's care when he was in the 4th grade because his parents struggled with drug addiction and could not provide for him. At thirteen, he was baptized in his aunt's faith as a Jehovah's Witness. Just days after he turned fourteen, on November 6, he was diagnosed with acute lymphoblastic leukemia.The prognosis was that Dennis had a 75% chance of cure with standard oncology treatment. Consistent with the requirements of his new faith, however, Dennis told his doctors, "I do not want to be treated if the requirement is that I would have to take a blood transfusion." His aunt, whose custodial rights seem not to have included medical decisionmaking, was adamant that "[t]his is Dennis's decision."The hospital social worker assigned to Dennis's case assured his aunt that "having just turned 14, [he] could be considered mature enough to make his own decisions." But hospital psychologists declined to evaluate Dennis's maturity because they did "not have the tools for such an assessment." Established hospital policy described the failure to provide a minor with necessary, life-saving care as medical neglect. Hospital ethicists advised that Dennis's autonomy interests were outweighed by the benefits associated with treatment. And, standard oncology practice norms are that doctors should push back against minors' lifesaving treatment refusals. Still, Dennis's doctor agreed with his social worker and aunt, saying, "We owe respect to a 14-year-old[.]" In this view, he was supported by colleagues on staff and by hospital counsel.A county judge got the case only at the eleventh hour, on an emergency motion filed by Dennis's parents and Child Protective Services for a declaration of dependency and to compel the necessary transfusion. Although Dennis was degrading rapidly, his doctor testified that if a transfusion were ordered that day, Dennis still had a 70% chance of survival. The judge had no background in the applicable law and no time to research the issues; nevertheless, he denied the motion concluding, "It is time to do what Dennis has decided." "Seven hours later, at 6 p.m., on Nov. 28, Dennis died."1.

The emphasis on clinical volume in physician compensation plans has diminished professional vitality in academic medical centers and increased the cost of health care. Physician incentive compensation plans that focus on clinical volume can distort clinical encounters and fail to incorporate the professionalism and intrinsic motivators of clinicians. We assert herein that physician incentive compensation plans should reward clinical value (quality/cost) rather than clinical volume. The recommended change is compelled by the tenets of medical professionalism, the need to cultivate meaning in clinical practice, and the urgent financial and moral imperatives to improve health outcomes and reduce cost. The design of physician incentive compensation plans should incorporate accurate and valid measures of quality and cost, behavioral economic considerations, transparency and equity, prospective assessment of the impact on key outcomes, and flexible elements that encourage innovation and preserve fidelity to unique practice circumstances. Physicians should be recognized in compensation plans for enhancing the value of care, inspiring and educating the future clinical workforce, and improving public health through discovery., (Copyright © 2021. Published by Elsevier Inc.)

Heat shock protein 90 (Hsp90) is a ubiquitous signal transduction regulator, and Hsp90 inhibitors are in clinical development as cancer therapeutics. However, there have been very few studies on the impact of Hsp90 inhibitors on pain or analgesia, a serious concern for cancer patients. We previously found that Hsp90 inhibitors injected into the brain block opioid-induced antinociception in tail flick, paw incision, and HIV neuropathy pain. This study extended from that initial work to test the cancer-related clinical impact of Hsp90 inhibitors on opioid antinociception in cancer-induced bone pain in female BALB/c mice and chemotherapy-induced peripheral neuropathy in male and female CD-1 mice. Mice were treated with Hsp90 inhibitors (17-AAG, KU-32) by the intracerebroventricular, intrathecal, or intraperitoneal routes, and after 24 hours, pain behaviors were evaluated after analgesic drug treatment. Heat shock protein 90 inhibition in the brain or systemically completely blocked morphine and oxymorphone antinociception in chemotherapy-induced peripheral neuropathy; this effect was partly mediated by decreased ERK and JNK MAPK activation and by increased protein translation, was not altered by chronic treatment, and Hsp90 inhibition had no effect on gabapentin antinociception. We also found that the Hsp90 isoform Hsp90α and the cochaperone Cdc37 were responsible for the observed changes in opioid antinociception. By contrast, Hsp90 inhibition in the spinal cord or systemically partially reduced opioid antinociception in cancer-induced bone pain. These results demonstrate that Hsp90 inhibitors block opioid antinociception in cancer-related pain, suggesting that Hsp90 inhibitors for cancer therapy could decrease opioid treatment efficacy.

The availability of new techniques and technologies to answer important medical questions is accelerating at a breathtaking pace. In response to these exciting new opportunities, clinical departments, in general, and departments of medicine, in particular, have broadened their research portfolios. Organization of the traditional structures of clinical departments, research infrastructure, training programs, and rewards for faculty has only begun to catalyze emerging research areas such as artificial intelligence, bioinformatics, bioengineering, cell and tissue engineering, cost effectiveness, health services, implementation science, integrative epidemiology, medical informatics, nanomedicine, and quality improvement. Success in these emerging areas of research requires interdisciplinary collaboration on a much larger scale than in the past. The effectiveness of efforts to recruit, develop, mentor, and promote faculty in these exciting areas will be critical to the success of departmental and institutional research programs. We describe examples of initiatives from our 5 departments of medicine designed to develop and promote faculty conducting research in emerging interdisciplinary areas. We focus on core resources, training, organizational structures, and recognition and promotion. Faculty have a compelling opportunity and obligation to pursue emerging research areas that have the potential to further improve the prevention, diagnosis, and treatment of disease. As departments prepare to meet this exciting opportunity in the future, the lessons learned must inform investments in faculty development. Although many of the strategies outlined herein could and should expand beyond any individual department, departments of medicine have a distinct obligation and opportunity to lead this effort., (Copyright © 2018. Published by Elsevier Inc.)

Thrombotic microangiopathy (TMA) is characterized by the presence of microangiopathic hemolytic anemia and thrombocytopenia along with organ dysfunction, and pathologically, by the presence of microthrombi in multiple microvascular beds. Delays in diagnosis and initiation of therapy are common due to the low incidence, variable presentation, and poor awareness of these diseases, underscoring the need for interdisciplinary approaches to clinical care for TMA. We describe a new approach to improve clinical management via a TMA team that originally stemmed from an Affinity Research Collaborative team focused on thrombosis and hemostasis. The TMA team consists of clinical faculty from different disciplines who together are charged with the responsibility to quickly analyze clinical presentations, guide laboratory testing, and streamline prompt institution of treatment. The TMA team also includes faculty members from a broad range of disciplines collaborating to elucidate the pathogenesis of TMA. To this end, a clinical database and biorepository have been constructed. TMA leaders educate front-line providers from other departments through presentations in various forums across multiple specialties. Facilitated by an Affinity Research Collaborative mechanism, we describe an interdisciplinary team dedicated to improving both clinical care and translational research in TMA., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Academic clinical departments have the opportunity and responsibility to improve the quality and value of care and patient safety by supporting effective quality improvement activities. The pressure to provide high-value care while further developing academic programs has increased the complexity of decision making and change management in academic health systems. Overcoming these challenges will require faculty engagement and leadership; however, most academic departments do not have a sufficient number of individuals with expertise and experience in quality improvement and patient safety (QI/PS). Accordingly, the authors of this article advocate for a targeted and proactive approach to developing faculty working in QI/PS. They propose a strategy predicated on the identification of QI/PS as a strategic priority for academic departments, the creation of enabling resources in QI/PS, and the expansion of rigorous training programs in change management and in improvement and implementation sciences. Professional organizations, health systems, medical schools, and academic departments should recognize successful QI/PS work with awards and promotions. Individual faculty members should expand their collaborative networks, consider the generalizability and scholarly impact of their efforts when designing QI/PS initiatives, and benchmark the outcomes of their performance. Appointments and promotions committees should work proactively with department and QI/PS leaders to ensure that outstanding achievement in QI/PS is defined and recognized. As with the development of physician-investigators and clinician-educators, departments and health systems need a comprehensive approach to support and recognize the contributions of faculty working in QI/PS to meet the considerable needs and opportunities in health care.

The authors described the features of a hypothetical academic Department of Medicine in 2030 that would be most effective in improving the public health. Future departments of medicine will be compelled to respond to a projected shortage of physicians through augmented training strategies. The clinical programs will be more decentralized and responsive to patient preferences while demonstrating greater value. Departments will create adaptable, accountable structures in which clinicians working in interdisciplinary teams continuously improve processes and outcomes of care, and clinician and patient satisfaction. The restructuring of health care will afford exciting opportunities to align clinical and scholarly activities. The growing ability to link biological and clinical phenotypic information will lead to more effective and efficient clinical care. In view of the funding constraints and the remarkable opportunities for high-impact research, departmental research programs will become increasingly disciplined. Successful research programs will require durable investments in faculty career development, enabling infrastructure, interdisciplinary research teams, and diverse funding sources. The educational programs will demonstrate proficiency of trainees in the 6 current core competencies, as well as in additional areas critical to health care transformation. To improve organizational effectiveness, departments will create more nimble organizational structures led by individuals with diverse backgrounds. Chairs of departments of medicine will be expected to continuously expand their capacity to meet the evolving needs of their departments and institutions. Members of departments of medicine will be continuously fortified by the privilege and obligations of our profession while embracing the risks necessary to meet the extraordinary opportunities in 2030., (Copyright © 2016 Alliance for Academic Internal Medicine. Published by Elsevier Inc. All rights reserved.)

The nature and scope of mature adolescents' legal authority to consent to general medical treatment without parental involvement is often misrepresented by commentators. This state of affairs is further complicated by the law itself, which has developed a broad "mature minor exception" to the general requirement of parental consent in abortion cases and which has additionally carved out numerous specific status-based and condition-based exceptions to that requirement. In these circumstances, it is not always a simple matter for physicians and other medical professionals who treat adolescents to ascertain the applicable law. In this article, we discuss the underlying differences between medical ethics and law, which have caused some of the confusion in this area, and we set out the most current legal rules governing adolescent decision-making authority in general medical settings. A comprehensive analysis of both statutory and common law demonstrates that in such settings, parental consent continues to be required by most jurisdictions, even when the minor can be considered cognitively "mature."

We have sought to broaden our department's research capacity using two different interdisciplinary approaches. First, we created the Evans Center for Interdisciplinary Biomedical Research (ECIBR) - a virtual center that promotes and funds Affinity Research Collaboratives (ARCs) initiated by faculty from within and outside Boston University (BU). Of the 11 funded ARCs, the 4 ARCs in existence for a minimum of 3 years have a total of 37 participants, 93 co-authored publications, and 33 new grants. Second, the Department of Medicine (DOM) created a Section of Computational Biomedicine in 2009 to enhance analytical and computational expertise in the DOM. After 3 years, the section is comprised of 10 faculty members and 21 trainees. The faculty members have collaborated with 20 faculty members in other sections or departments and secured 12 extramural grants (totaling ∼$20 million in direct costs). The ECIBR and the Section of Computational Biomedicine represent new organizational approaches to stimulating innovation in research in a DOM.

Key Indicators in Academic Medicine (KIAMs), a new feature in Academic Medicine, are intended to substantially inform teaching hospitals and medical schools on those metrics that may best gauge their health, including the performance of units and programs within these organizations. Ultimately, KIAMs may promote effective growth and development in a dynamic clinical, training, and research environment. At the outset of this laudable feature, the authors of this perspective offer a suggested framework for analyzing key indicators with the goal of enhancing the usefulness of the published KIAMs. They outline their view of pitfalls and opportunities in the development of key indicators and suggest strategies. The authors close by suggesting how this feature could form the framework for a comprehensive national project.

The relationship between faculty in academic health centers (AHCs) and commercial entities is critically important to improving the public health, yet it may be prone to conflicts of interest that adversely affect medical education, research, and clinical care. The Association of American Medical Colleges has recently recommended that medical schools and AHCs develop policies that better manage and occasionally prohibit interactions between academic medicine and industry. Because the development of more stringent policies is complex and potentially contentious, the author reports the lessons learned from developing new policies for the interactions between faculty and industry related to medical education and clinical care at Yale School of Medicine and Boston University School of Medicine/Boston Medical Center. The content of the policies was strongly influenced by the tenets of medical professionalism. Faculty support for new policies was strong, an iterative and inclusive process of formulation was critical, compromises in content were necessary, and the views of faculty concerning industry relationships were complex. After implementation of the new policies, the departmental food-related expenses increased, the loss of gifts was not appreciably missed, the faculty assumed more responsibility for educating trainees on the evaluation of new products, a central repository for receiving and evaluating grants from industry was useful, enforcement of the policies has been a lingering challenge, and the new policies generated positive publicity. Several recommendations are proposed. Creating these policies affirmed the importance of an inclusive process, open communication, support of institutional leadership, and focus on professional values.

Since the mid- to late 1990s, the scientific and medical research community has sought to increase its access to healthy children for research protocols that involve harm or a risk of harm. This move reverses longstanding policy within that community generally to exclude healthy children from such protocols on the grounds that the research as to them is non-therapeutic, that they are particularly vulnerable to research-related abuses, and that they are unable themselves to give informed consent to their participation. The research community's new posture has been supported by prominent pediatric bioethicists who have argued that unless healthy children are included as research subjects in harmful or risky research, the pediatric population will continue to suffer relative to the adult population in the extent to which it benefits from modern advances in science and medicine. In their view, it is possible for the research community to self-administer a rule that strikes a balance between protecting healthy children from research-related abuses and allowing their inclusion in cutting-edge pediatric research. In this scheme, parental consent is central to the research community's claims about child protection. This Article explores the flaws inherent in this ethics of pediatric research. Specifically, it challenges the view from ethics that the law permits parents to consent to their children's inclusion in harmful or risky research to the extent that related invasions would meet legal maltreatment standards. More broadly, it challenges the movement to increase access to healthy children for harmful and risky research on the ground that it risks two important regressions: First, in its willingness to risk harm to individual children in the interests of the group, it threatens the progress the law has made in its development of the concept of the child as an individual worthy of respect in his or her own right, a concept that imagines parents as fiduciaries and that includes strong protections against invasions of bodily integrity. Second, in its failure to assure that the burdens of non-therapeutic research are not placed disproportionately on children of lower socioeconomic and minority status, it violates the antidiscrimination principle, which has only begun to make good on its promise of equal treatment for all children. Ultimately, this Article argues that harmonization of the rules governing pediatric research with the law of child protection and parents' consent authority is the best way to assure that children are protected in the research setting in these respects and to the same extent they are otherwise in the society.

In April 2004, a questionnaire was distributed to veterinary nurses across the UK to assess their attitudes towards the assessment and management of pain in practice. During the six-week collection period, a total of 541 questionnaires were returned, of which 24 (4.25 per cent) were discounted due to completion errors. Overall, the pain scores for procedures involving dogs were higher than those for cats; the veterinary nurses' pain scores were higher for all procedures than those of veterinary surgeons in a previous study. Both veterinary nurses and veterinary surgeons were primarily involved with monitoring pain postoperatively, and 96 per cent of veterinary nurses felt that their knowledge of pain management could be enhanced; 8.1 per cent of the practices used a formal pain scoring system, with the simple descriptive scale most commonly used; 80.3 per cent of the veterinary nurses agreed that a pain scale was a useful clinical tool.

The lack of health insurance has significant deleterious effects on the health of individual patients and creates substantial financial pressure on health care institutions. Despite the historical role of academic medical centers (AMCs) and medical schools in caring for the uninsured, financial shortfalls have increased pressure on these institutions to restrict care of this population. Limiting care of the uninsured, however, conflicts with the ethical foundations of academic medicine and risks further harm to the health of this population. Instead of restricting care, the effects of uninsurance should be mitigated through the joint efforts of medical schools and AMCs by measuring clinical work using work Relative Value Units rather than collections; recognizing faculty who provide care for the uninsured in the promotions process; adjusting billing rates for clinical services according to patients' ability to pay; delivering one standard of care irrespective of insurance status; continuing to evaluate the impact of uninsurance and intervention strategies; providing leadership in measuring and improving the quality of care; ensuring that trainees and the public are familiar with the effects of a lack of health insurance; and assisting safety net providers by providing educational materials pertinent to their respective patient populations and more fully integrating these providers into the academic community. Although all physicians in the private and public sectors should share in the care of the uninsured, academic medicine must remain faithful to its historical role of providing care to the uninsured and should improve the health of the uninsured through a proactive strategy involving advocacy, clinical care, education, and research.

Purpose: Academic internal medicine practices face growing challenges to financial viability due to high overhead, competing institutional missions, and suboptimal physician productivity. The authors describe the development of a clinical incentive plan for a group of academic subspecialty physicians at the Dana Clinic, an outpatient setting at Yale School of Medicine, and report on results of the first year's experience under the plan., Method: Utility theory was used to assess the risk profile of clinic faculty and identify incentive payments that would optimize faculty benefit or "utility" while minimizing departmental costs. Under the plan, physicians who reached a productivity target based on work Relative Value Units (wRVUs) between October 2003 and November 2004 had overhead costs covered and received a fixed payment to support salary; additional incentive payments were available for those exceeding the target. Physicians failing to reach the target were responsible for their own overhead costs and received no fixed payment. Physician productivity as measured by wRVU per full-time equivalent (FTE) was compared for the year prior to, and the year following, incentive plan introduction., Results: Forty-seven members of eight academic sections were included in the analysis. Median productivity improved by 34%, with 42 of 47 physicians showing improvement. Significant improvements were also noted in collections (62%) and visit volume (23%), and shifts were observed in coding patterns., Conclusions: The unique threshold-based structure of the incentive plan, as determined through utility theory modeling, as well as permitting physicians to choose how to achieve the wRVU target were key features of its success, resulting in improved productivity without increasing practice resources or faculty salaries.

A productive and ethical relationship between the pharmaceutical industry and physicians is critical to improving drug discovery and public health. In response to concerns about inappropriate financial relationships between the pharmaceutical industry and physicians, national organizations representing physicians or industry have made recommendations designed to reduce conflicts of interest, legal exposure, and dissemination of biased information. Despite these initiatives, the prescribing practices of physicians may be unduly influenced by the marketing efforts of industry and physicians may inadvertently distribute information that is biased in favor of a commercial entity. Moreover, physicians may be vulnerable to prosecution through federal anti-kickback and false claims statutes because of potentially inappropriate financial relationships with pharmaceutical companies. Since academic medical centers have a critical role in establishing professional standards, the faculty of Yale University School of Medicine developed guidelines for the relationships of faculty with the pharmaceutical industry, which were approved in May 2005. Input from clinical faculty and from representatives of the pharmaceutical industry was utilized in formulating the guidelines. In contrast to existing recommendations, the Yale guidelines, which are presented as an Appendix here, ban faculty from receiving any form of gift, meal, or free drug sample (for personal use) from industry, and set more stringent standards for the disclosure and resolution of financial conflict of interest in Yale's educational programs. The growing opportunities for drug discovery, the need to use medications in a more evidence-based manner, and preservation of the public trust require the highest professional standards of rigor and integrity. These guidelines are offered as part of the strategy to meet this compelling challenge.

The mission of the Department of Veterans Affairs includes patient care, education, research, and backup to the Department of Defense. Because the measurement of physicians' productivity must reflect both institutional goals and market forces, the authors designed a productivity model that uses measures of clinical workload and academic activities commensurate with the VA's investments in these activities. The productivity model evaluates four domains of physicians' activity: clinical work, education, research, and administration. Examples of the application of the productivity model in the evaluation of VA-paid physician-staff and in the composition of contracts for clinical services are provided. The proposed model is a relatively simple strategy for measuring a broad range of the work of academic physicians in VA medical centers. The model provides incentives for documentation of resident supervision and participation in administrative activities required for effective and efficient clinical care. In addition, the model can aid in determining resource distribution among clinical services and permits comparison with non-VA health care systems. A strategy for modifying the model to incorporate measures of quality of clinical care, research, education, and administration is proposed. The model has been a useful part of the process to ensure the optimum use of resources and to meet clinical and academic institutional goals. The activities and accomplishments used to define physician productivity will have a substantial influence on the character of the medical profession, the vitality of medical education and research, and the cost and quality of health care.

The scholarship of application encompasses a broad range of different types of scholarship in the sciences and humanities that involves translation of new knowledge to practical applications to solve problems of individuals and of society. The authors discuss this form of scholarship broadly, but focus on how it applies to patient-oriented research and to service performed by physicians. They distinguish between a clinician's use of his or her expertise (not scholarship) and a clinician's activities such as systematically assessing the effectiveness of different techniques and communicating the findings in a way that allows others to benefit (scholarship). They (1) review the importance of scholarship of application (i.e., society depends on the application of new knowledge), with special attention to the benefits to academic institutions; (2) discuss incentives for such scholarship (e.g., readiness of funding for directly applicable research) and disincentives (e.g., shortcomings in methods; lower prestige); (3) explain how it should be evaluated (create a more expansive peer-review process); (4) explain how it should be rewarded (rewards should be similar to those given for other forms of scholarship); and (5) describe how it should be nurtured (rigorous training in methodology, protected time for research, tangible support). They conclude that the interdependence of academic institutions and of society requires that the scholarship of application be conducted with rigor and relevance, and that institutions must develop strategies to promote applied scholarship.

LY309887, a reduced analogue of folic acid, is a potent inhibitor of glycinamide ribonucleotide formyltransferase and possesses a broad spectrum of antitumor activity. During preclinical studies using supplementation with oral folic acid, this second-generation inhibitor displayed both the desired safety profile and the pharmacology to warrant clinical investigation. A sensitive analytical method was needed to assess the pharmacokinetics of LY309887 due to the low doses planned for Phase I studies and the potential for low concentrations in plasma long after i.v. administration. We therefore undertook the development of a competitive RIA. A highly specific antiserum was raised in rabbits following immunization with LY309887 coupled to BSA. A RIA tracer was prepared by radioiodination of compound 389753, the adduct of LY309887 with p-tyramine. We developed a competitive-binding RIA procedure and used superparamagnetic particles coated with goat antirabbit IgG as a method for separating the bound and free forms of LY309887. The RIA is sensitive (0.5 ng/ml in serum and 25 ng/ml in urine), specific (negligible interference from endogenous folates), and reproducible (interassay coefficients of variation ranging from 8.1 to 15.4% and 7.6 to 8.3% for serum and urine controls, respectively). We used the RIA to assess the i.v. pharmacokinetics of LY309887 in both patients with metastatic cancer and dogs. The sensitivity of the RIA permitted the demonstration that serum concentrations of LY309887 decline in a multiexponential manner with a prolonged terminal elimination phase. We conclude that the RIA is a valid method for quantifying LY309887 in biological fluids.

Glomerular epithelial cells (GEC) and mesangial cells (MC) are both involved in glomerular diseases. To elucidate potential interactions between these glomerular cell types, we examined whether products of GEC affect the proliferative activity of MC. We found that cultured rat GEC secrete soluble factors into the supernate (GEC-CM) that induce proliferation of quiescent rat MC. The mitogenic activity was trypsin sensitive and partially heat-labile. Biochemical analysis of GEC-CM by gel filtration HPLC, reverse phase HPLC, and isoelectric focusing revealed at least three mitogenic fractions as well as inhibitory activity present in GEC-CM. Competitive binding assays with 125I-labeled PDGF did not show significant amounts of PDGF in GEC-CM. The biochemical features of the GEC-derived MC growth factors are distinct from IL-6, PDGF, bFGF, and endothelin, previously described GEC-derived MC growth factors. Additionally, significant contributions of known growth factors such as IL-1, IL-2, IL-3, IL-4, IL-5, TNF alpha, TGF beta, and GM-CSF are unlikely. The results indicate that GEC produce several biochemically-distinct MC growth regulators. While these epithelial cell-derived mitogens for MC require further characterization, they may play an important role in the regulation of MC replication, such as during embryogenesis and glomerular disease.