Search

Background Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a complication of severe influenza and coronavirus disease 2019. The extent to which other respiratory viral infections (RVIs) predispose to IPA is unclear. Methods We performed a retrospective review of IPA occurring within 90 days of respiratory syncytial virus (RSV), parainfluenza, or adenovirus infections (noninfluenza respiratory viral infections [NI-RVIs]) in patients who underwent solid organ transplant between 1/15/2011 and 12/19/2017. Results At a median post-transplant follow-up of 43.4 months, 221 of 2986 patients (7.4%) developed 255 RSV, parainfluenza, or adenovirus infections. IPA complicating these NI-RVIs was exclusively observed in lung and small bowel transplant recipients, in whom incidence was 5% and 33%, respectively. Cumulative prednisone doses >140mg within 7 days and pneumonia at the time of NI-RVI were independent risk factors for IPA (odds ratio [OR], 22.6; 95% CI, 4.5–112; and OR, 7.2; 95% CI, 1.6–31.7; respectively). Mortality at 180 days following NI-RVI was 27% and 7% among patients with and without IPA, respectively (P = .04). Conclusions In conclusion, IPA can complicate RSV, parainfluenza, and adenovirus infection in lung and small bowel transplant recipients. Future research is needed on the epidemiology of IPA complicating various RVIs. In the interim, physicians should be aware of this complication.

Background Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101). Methods The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4–17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003, and is completed. Findings Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101–placebo treatment difference 56·0% [95% CI 44·1–65·2], p

Since the enactment of the Dodd-Frank Act in 2010, U.S. bank regulation and bankruptcy have become far more closely intertwined. In this Article, I ask whether the new synthesis of bank regulation and bankruptcy is coherent, and whether it is likely to prove effective.I begin by exploring some of the basic differences between bank resolution, which is a highly administrative process in the U.S., and bankruptcy, which relies more on courts and the parties themselves. I then focus on a series of remarkable new innovations designed to facilitate the rapid recapitalization of systemically important financial institutions: convertible contingent capital securities (“CoCos”); single point of entry resolution under the Dodd-Frank Act; and the quick sale strategy in bankruptcy. I conclude that the early trigger CoCos advocated by Calomiris and Herring and others are the most promising strategy for CoCos, and assess the virtues and potential pitfalls of single point of entry and quick sales. I conclude by considering the general coherence of the new synthesis. The most important frictions lie in the relationship between the Dodd-Frank Act’s resolution provisions and bankruptcy. While their differing treatment of managers could create beneficial incentives to use bankruptcy rather than resolution under the Dodd-Frank rules, the absence of a stay on derivatives in Chapter 11 diminishes the effectiveness of the new synthesis.I argue that the overall objective of the new synthesis should be to funnel large, troubled financial institutions toward bankruptcy wherever possible.

Joan McCracken leaves the Littlefields to perform at Radio City Music Hall and eventually on Broadway. Catherine stages dances for the large-scale “American Jubilee” pageant at the World’s Fair in New York in 1940. Her innovative bicycle ballet in the pageant is a tremendous hit. Al Jolson hires her for his comeback show on Broadway, Hold On to Your Hats. She is then enlisted to choreograph ice-skating routines for New York’s Center Theatre, which has been converted into an ice theater by Chicago entrepreneur Arthur Wirtz and his business partner, Olympic skating champion Sonja Henie. Wirtz soon installs Catherine as choreographer for Henie’s touring Hollywood Ice Revues as well. She takes her Littlefield Ballet on an eight-week national tour. She and Philip officially separate, although they remain friends and business associates. She and her Littlefield Ballet return to Chicago for the 1941 opera season. The company disbands after Pearl Harbor is bombed and many of Catherine’s male dancers, including Carl, enlist in the military.

Spinal cord injury (SCI) is a widely disabling condition, constraining those affected by it to wheelchairs and requiring intense daily care and assistance. Cell replacement therapies, targeting regeneration of cells in the injured cord, are currently gaining momentum in the field of SCI research. Previous studies indicate that mesenchymal stem cells (MSCs) can reduce functional deficits through immunomodulation and production of trophic factors in a variety of neurological disorders. The present study assessed the efficacy of transplanted bone marrow–derived MSCs at different concentrations and locations for promoting functional recovery following SCI. Although effects were modest, MSCs facilitated an increase in the base of support, as measured by increased distance between the plantar surface of the hind paws, following incomplete contusive SCI, and reduced the density of astroglial scarring. Varying the concentrations or locations of transplanted cells did not provide additional benefits on these measures. These findings indicate that MSC transplants are safe at relatively high concentrations and confer therapeutic benefits that, when used as an adjunctive treatment, could significantly enhance functional recovery following SCI.

The inappropriate use of opioids in the United States has increased markedly and has resulted in a tragic loss of lives. To combat this problem, prescription drug monitoring programs (PDMPs) have been instituted in most states. Use of the programs is voluntary for prescribers in some states, whereas in other states it is mandatory. The current study used a self-report survey instrument that was administered to 223 participant physicians. The goal of the study was to compare awareness and use of the PDMP in a state that mandates use (Ohio) with one that does not (North Carolina). Although awareness was not significantly different between respondents from the two states, self-reported use was significantly higher in the state mandating use (Ohio post-mandate vs. Ohio pre-mandate: 64% vs. 51%; χ

e17564 Background: Different dosing schedules of CDDP are being used as standard of care for CCRT in LA-SCCHN, but there are no adequately powered trials to directly compare other non-CDDP regimens with CDDP to identify the optimal CCRT regimen. Methods: After obtaining IRB approval, we reviewed medical records from hospital tumor registry for consecutive patients with LA-SCCHN to retrieve data regarding demographics, diagnosis and treatment with definitive CCRT between December 2012 and December 2016. All patients had followed up for at least 24 months after completion of treatment. Results: 155 patients were included in the analysis. They fell into 2 groups: 89 (57.4%) had been administered CDDP and 66 (42.6%) received non-CDDP based regimen. In the latter group, 30 (45.5%) received cetuximab, 30 (45.5%) received carboplatin with paclitaxel, 1 (1.5%) received carboplatin with 5-fluorouracil and 5 (7.6%) received carboplatin alone. The majority of patients in both groups had oropharyngeal involvement, approximately 65%. All patients completed treatment with intensity-modulated radiation therapy. Median age was 57 years in CDDP group and 67 years in non-CDDP group. Patients in both groups were predominantly male, Caucasian, with positive smoking history. 67% patients in CDDP & 59% in non-CDDP group were HPV positive. The 2-year overall survival (OS) from initiation of treatment was 73.9% in CDDP and 62.1% in non-CDDP group (hazard ratio = 1.63, 95% CI 0.92 – 2.87, p = 0.092). Comparing non-CDDP regimens with CDDP, cetuximab appeared to confer better 2 year OS in HPV positive patients (HR 0.63, 95% CI 0.40 – 0.98, p = 0.040). Median time-to-treatment failure was 33 months in CDDP group and 24 months in non CDDP group. Conclusions: In this retrospective comparison, there was no significant difference in the 2 year overall survival in patients with locally advanced squamous cell head and neck cancers being treated with cisplatin based concurrent chemoradiotherapy regimen versus a non-cisplatin based regimen.

This paper articulates a framework both for assessing the various government bailouts that took place at the onset of Great Recession and for guiding future rescue efforts when they become necessary. The goals for those engineering a bailout should be to be as transparent as possible, to articulate clearly the reason for the intervention, to respect existing priorities among investors, to exercise control only at the top level where such efforts can be seen by the public, and to exit as soon as possible. By these metrics, some of the recent bailouts should be applauded, while others fell short. We also explore the related question of what level of judicial scrutiny is appropriate for government actions taken during a bailout. We eschew the extremes of no judicial review on the one hand and full recourse to the courts on the other. Courts need to avoid interfering in a time of crisis, yet, when normalcy has returned, they should measure the actions taken against applicable legislative and constitutional requirements.

In 2011, 5 years after the implementation of a statewide prescription monitoring program (PMP) in Ohio, a survey was distributed to physicians in five specialty areas. During the study period, 95 of 156 surveys were returned, for a 61% response rate. The purpose of the questionnaire was to assess utilization rates as well as reasons for accessing the PMP database and any influence the database may have had on prescribing practices. Over 84% of respondents were aware of the existence of the state PMP. However less than 59% of the respondents who were aware of the program had ever used it. Medical specialty was found to have a significant impact on both awareness and utilization of the system, with pediatric physicians least likely, and emergency physicians most likely, to be aware of and utilize the state PMP. Recommendations based on the authors' survey results include targeting pediatric and internal medicine providers for increased education regarding awareness and benefits of PMP utilization.

Giving bad news has been identified by physicians as a difficult task. This study compares the skills of first-year medical students to those of third-year students that had received training in giving bad news using role-play with standardized patients. Observers completed a checklist developed to determine student skill level.

Malignant melanoma is the most aggressive cutaneous malignancy with dismal prognosis in the advanced setting. The food and drug administration approval of ipilimumab, the monoclonal antibody against cytotoxic T-lymphocyte antigen 4, has significantly changed treatment strategies for this disease. However, the spectrum of immune-related adverse events secondary to ipilimumab therapy is a growing area of research, and clinical observations of rare immune events as a result of such therapies continue to be reported since the approval. The co-occurrence of disease progression along with an immune-related adverse event is extremely rare. We here present the first case, to our knowledge, of diffuse nonnecrotizing granulomatous lymphadenopathy occurring simultaneously with disease progression in a patient with metastatic melanoma after receiving the second dose of ipilimumab.

Background: Healthcare-related errors cause patient morbidity and mortality. Despite fear of reprimand, laboratory personnel have a professional obligation to rapidly report major medical errors when they are identified. Well-defined protocols regarding how and when to disclose a suspected error by a colleague do not exist.Patient: We describe a woman with a well documented allergy to sulfamethoxazole who was treated with sulfadiazine that led to toxic epidermal necrolysis. After the patient’s death, the laboratory medicine resident was asked by one of the patient’s physicians to measure serum sulfadiazine, but only if the results were not reported in the patient’s electronic medical record. The case was brought to the attention of a laboratory medicine faculty member and the hospital risk management team.Issues: Laboratorians are patient fiduciaries and are responsible for reporting errors. Most medical associations have codes of ethics that address disclosure of incompetence and errors, although the AACC’s Guide to Ethics does not. New types of error, risk management, and root-cause analyses help to shift the focus to system errors and away from individuals’ errors. This can lead to a healthcare environment that encourages truth and disclosure rather than fear and reprimand.Disposition: The individuals involved in the presented case fulfilled their fiduciary duty to the patient by reporting this incident. An extensive investigation showed that, in fact, no medical errors or misconducts had occurred in the care of the patient.

NAMD is a parallel molecular dynamics code designed for high-performance simulation of large biomolecular systems. NAMD scales to hundreds of processors on high-end parallel platforms, as well as tens of processors on low-cost commodity clusters, and also runs on individual desktop and laptop computers. NAMD works with AMBER and CHARMM potential functions, parameters, and file formats. This article, directed to novices as well as experts, first introduces concepts and methods used in the NAMD program, describing the classical molecular dynamics force field, equations of motion, and integration methods along with the efficient electrostatics evaluation algorithms employed and temperature and pressure controls used. Features for steering the simulation across barriers and for calculating both alchemical and conformational free energy differences are presented. The motivations for and a roadmap to the internal design of NAMD, implemented in C++ and based on Charm++ parallel objects, are outlined. The factors affecting the serial and parallel performance of a simulation are discussed. Finally, typical NAMD use is illustrated with representative applications to a small, a medium, and a large biomolecular system, highlighting particular features of NAMD, for example, the Tcl scripting language. The article also provides a list of the key features of NAMD and discusses the benefits of combining NAMD with the molecular graphics/sequence analysis software VMD and the grid computing/collaboratory software BioCoRE. NAMD is distributed free of charge with source code at www.ks.uiuc.edu.

Lymphoplasmacytic lymphoma is a chronic lymphoproliferative disorder characterized by a proliferation of plasma cells, small lymphocytes, plasmacytoid lymphocytes and the production of monoclonal IgM. Primary central nervous system lymphomas (PCNSL) are rare non-Hodgkin lymphomas (NHL) that can be found in the brain, leptomeninges, eyes or spinal cord, and are mostly intracerebral. PCNSLs constitute 3-4% of primary brain tumors, and in most cases are diffuse large B-cell lymphomas (DLBCL).(1) Low grade lymphomas as primary central nervous system (CNS) lymphoma are very rare. We present here a case report of a woman who presented with headache and was found to have primary intracranial lymphoplasmacytic lymphoma (LPL).

Twenty-five years of research on family care to dependent elders has produced a theoretically sophisticated understanding of the process of family caregiving. Although caregiving models initially were developed and tested on predominantly White samples, more recent work has applied these models to African American caregivers. This investigation builds on the comparative perspective by describing elder care in African American families through the eyes of the culture in which it occurs. Thirty-two African American caregivers were interviewed and asked to discuss their caregiving careers from a life course perspective. Qualitative narratives described three pathways to care: elder care only, limited life course of care, and live course of care. Recognition of the various pathways to care will enlighten tailored interventions.

Purpose. Combined biological therapy with 13-cis-retinoic acid (13-cRA) and interferon alpha-2a (IFN α-2a) was reported to be highly effective in squamous cell carcinoma of the cervix and skin. Squ...

This article explores three different kinds of reforms that could be used to help governmental corporations achieve some of the benefits of privatized, market-based governance without giving up governmental control. The first, and simplest, proposal is to use an annual contract between GOC managers and their ministerial shareholders to reduce managerial agency costs. In addition to providing a benchmark for managerial performance, the contract also could be used to segment the GOC's different goals in order to minimize the downside effects of having multiple principals (with multiple objectives) monitoring the manager-agents. Second, I suggest that requiring at least some GOC's to issue subordinated debt would create a class of private investors who could provide additional monitoring as well as market signals about the prospects of the firm. Finally, I focus on various boundary problems with GOC's, as compared to private firms. I argue that GOC's should be required to set up separate subsidiaries when they expand into new product areas. Requiring the GOC to set up a separate subsidiary would make it much easier to police inappropriate cross subsidization.

8524 Background: The optimal treatment of patients with Stage IIIA NSCLC, a heterogeneous group comprised of T1-T4, N0-N2 disease, is controversial. Lack of clear data and guidelines allows several options for treatment, and hence there has been significant variability in clinical practice. The purpose of this study was to evaluate the nationwide trends in rates of surgery for Stage IIIA lung cancer diagnosed between 2000-2013. Methods: The study included patients with Stage IIIA NSCLC, 18 years and older diagnosed between 2000 and 2013. We used Z-tests in SEER*Stat to compare relative survival rates for patients diagnosed between 2000-2010. Results: Among the 27,697 patients with Stage IIIA NSCLC, 45% were females and median age was 67. 35% were treated with surgery. Multivariate analysis demonstrated that year of diagnosis, race, marital status, geographic region, tumor size, tumor grade, nodal status all were significantly associated with the use of surgery. Relative survival at 24 months (RS24) was 62% for patients who had surgery and 29% for patients without surgery (z = -47.3). The proportion of patients receiving surgery decreased from 55.6% in 2000 to 32.6% in 2010 and 29.7 in 2013 (p < 0.0001) while the relative survival at 24 months (RS24) from 2000 to 2010 rose from 34.7% to 43.2% (z = -4.89). The RS24 for patients who received surgery rose from 55.3% in 2000 to 77.6 % in 2010 (z = -3.58). Change in RS24 for patients who did not have surgery also improved from 19.6% to 31.2%. The median RS of the surgical cohort changed from 28 m to 44 m. Conclusions: Based upon reporting within the SEER database, the proportion of stage IIIA NSCLC patients undergoing surgery has decreased over the study time period. However, the relative survival rates have improved significantly for both the overall group and those having surgery, suggesting that significant strides have been made both in selecting the group of patients who would benefit from surgical resection and in the overall management of this group of patients.

Purpose: Preclinical and clinical data support the studyof polar-planar compounds such as N-Methylformamide (NMF) inadvanced squamous cell carcinoma of the uterine cervix (SCC).This phase II trial sought to determine the efficacy andtoxicities of NMF in patients with advanced SCC. Patientsand methods: Eligibility for this trial requiredbidimensionally measurable squamous or adenosquamous cellcancer of the uterine cervix incurable by surgery or radiationtherapy, ECOG performance status of ≤2, no prior NMF and nomore than one prior chemotherapy regimen. Patients receivedNMF at 2000 mg/m2 intravenously over 15–30 minutes days 1,8 and 15. The cycle was repeated every 42 days. A single doseescalation of 25%, 500 mg/m2 was made after the firstcycle if the toxicities did not exceed grade I for hepatictoxicity and grade II for nausea and vomiting. Results:From July 1987 through September 1998, 21 patients withadvanced squamous cell carcinoma of the uterine cervix wereentered on study. Two patients were ineligible because therewas no pretreatment SGOT on one and the other deterioratedprior to drug approval. Therefore, 19 patients were include inthe analysis of response and survival. Four were inevaluable,3 due to inappropriate tumor evaluation and I secondary tograde III vomiting, who went off study. These patients wereincluded in the denominator while computing the results. Therewere 2 deaths, one due to pulmonary hemorrhage fromperforation during central venous insertion and one due todisease. 30% (6/19) patients had toxicities, EasternCooperative Oncology Group (ECOG) grade III or higher and 2 ofthese patients suffered multiple grade III toxicities. Therewere no complete or partial responses. Conclusion: Inthis population, NMF in the dose and schedule employedexhibited no clinical activity.

Purpose: Objectives of this study were to obtain data from Eastern Cooperative Oncology Group (ECOG) oncologists regarding their views on quality of life (QOL) information; perform psychometric testing on the MD-QOL questionnaire, develop a model to describe oncologists' willingness to use QOL information and propose data-based interventions to facilitate use of QOL information in clinical decision-making. Methods: A self-administered questionnaire, MD-QOL, designed to assess physician perspective on QOL information was mailed to a random sample of 500 oncologists, members of ECOG; 271 responded. Results: Oncologists' attitude, current behaviour, knowledge of QOL data, and reported willingness to use QOL can be measured using MD-QOL. The attitude, behaviour and willingness scales have high internal consistency. Physician attitude and behaviour account for 59% of the variance in the willingness to use QOL information. Demographic variables influencing physician responses were their primary income source and exposure to trials with a QOL component. Conclusions: This report of ECOG oncologists' views on QOL information suggests a model to describe relationship between physician willingness to use QOL information on the basis of their attitude and behaviour. Data-based interventions are proposed to influence the key variables and thus facilitate the incorporation of QOL data in clinical practice.

Purpose: The present study was conducted to investigate the efficacy and toxicity of a cisplatin and 5‐fluorouracil (5‐FU) combination in previously treated advanced breast cancer. Methods: Thirty‐six women with recurrent metastatic breast cancer were entered on a phase II study of 5‐FU 1000 mg/m2/day given intravenously as a continuous infusion on days 1–3 and cisplatin 30 mg/m2/day given intravenously over 1 h on days 2–4, repeated every 21 days. All subjects had received one previous chemotherapy regimen for metastatic disease and either progressed during treatment or relapsed after responding to previous chemotherapy. Fourteen patients had also received previous adjuvant chemotherapy, 17 patients had previous radiation therapy, and 29 patients had previous hormonal therapy. Results: Among 32 response‐evaluable patients, there were 10 partial remissions (31%) and 1 complete remission (3%), with an overall objective response rate of 34%. Median duration of response was 4 months. Median survival was 10.5 months for responders and 9.5 months for the entire group. Toxicity was mild to moderate in most patients. Overall twelve patients experienced grade 3 toxicity (10 hematologic, 1 mucositis, and 2 nausea). There were no grade 4 or 5 toxicities. Conclusion: Infusional cisplatin and 5‐FU is a well tolerated and active regimen in women with previously treated advanced breast cancer.

Thalidomide is one of the immunomodulating agents used in current oncology practice. We present a case of hemorrhagic rash induced by thalidomide in a patient with delta granule storage pool disease. The patient was getting thalidomide for underlying myelofibrosis.

The aim of the study was to evaluate the pretreatment workup of patients referred to our tertiary care center with low-grade lymphoma for compliance with National Comprehensive Cancer Network guidelines. This was a retrospective chart review. The study included all new patients with low-grade lymphoma who were diagnosed and treated at our center from January 1, 2005, to December 30, 2011. All the major facets of pretreatment workup were examined, including bone marrow biopsy, lactate dehydrogenase, hepatitis B screening, performance status of the patient, and diagnostic radiological studies. A total of 53 new patients were identified, of whom 36 (68%) had pretreatment workup and treatment at our center. The median age at diagnosis was 67. Fifty-four percent of the patients had bone marrow biopsy done. Radiological diagnostic studies were conducted in 97% of the patients. Hepatitis B screening was done in 19% of the total patients and 25% of the patients who received rituximab. Lactate dehydrogenase levels were checked in 72% of the patients. A significant deviation from the National Comprehensive Cancer Network guidelines for low-grade lymphoma pretreatment workup was observed for hepatitis B screening. Measures to ensure that patients have hepatitis B screening before rituximab were implemented. Studies such as these help to improve patient care.

A meeting of international finance and insolvency experts was held on November 2, 2013 at the Annenberg House in Santa Monica, California. The meeting was co-hosted by the USC Law School and the Annenberg Retreat at Sunnylands. The goal was to solicit the views of experts on the implications of the IMF’s April 26, 2013 paper captioned “Sovereign Debt Restructuring -- Recent Developments and Implications for the Fund’s Legal and Policy Framework”. The April 26 paper may signal a shift in IMF policies in the area of sovereign debt workouts. Although the Expert Group discussed a number of the ideas contained in the April 26 paper, attention focused on paragraph 32 of that paper. That paragraph states in relevant part: “There may be a case for exploring additional ways to limit the risk that Fund resources will simply be used to bail out private creditors. For example, a presumption could be established that some form of a creditor bail-in measure would be implemented as a condition for Fund lending in cases where, although no clear-cut determination has been made that the debt is unsustainable, the member has lost market access and prospects for regaining market access are uncertain.”This Report summarizes the consensus views of the Expert Group on the practical implications of the suggestions contained in paragraph 32 of the April 26 paper.

In this Essay, I take stock (as something of an outsider) of the behavioral economics movement, focusing in particular on its interaction with traditional cost-benefit analysis and its implications for agency structure. The usual strategy for such a project — a strategy that has been used by others with behavioral economics — is to marshal the existing evidence and critically assess its significance. My approach in this Essay is somewhat different. Although I describe behavioral economics and summarize the strongest criticisms of its use, the heart of the Essay is inductive, and focuses on a particular context: financial and securities regulation, as recently revamped by the Dodd-Frank Act and subsequent rule making. To lay the foundation for the Essay, I begin by briefly describing behavioral economics and by surveying the most significant critiques of its use. I then consider how behavioral economics has informed, or might inform, the work of the Consumer Financial Protection Bureau; SEC rulemaking on proxy access; and the efforts of the new financial legislation to ban bailouts. I suggest, among other things, that behavioralism’s implications are quite different for rules and rulemaking than for questions of regulatory structure.

Objective. The purpose of this study is to evaluate the influence of attending physician awareness and utilization of a state prescription monitoring program on resident physician behavior. Design. Twenty-five attending physicians and 70 residents in Emergency Medicine, Internal Medicine, Neurology, Pediatrics, and Psychiatry completed an 11-item questionnaire assessing awareness and utilization of a state prescription drug monitoring program. Results. Residents who used the system had, on average, a higher proportion of supervising attendings using the system; residents required to utilize the system had the highest proportion of attendings using the system. Overall, almost 90% of the physicians who utilized the system did so due to concerns surrounding prescription drug abuse. Over one third of attending physicians reported increasing the quantity or amount of medication prescribed after utilizing the system, while no residents reported similar outcomes. Conclusions. Through the behavioral influence of supervising attending physicians, residents were significantly more likely to utilize the system. If system utilization is desired, attendings should use the system and require resident participation.

For nearly two years, the two of us have had a running discussion of the costs and benefits of automatic stays in bankruptcy for qualified financial contracts (QFCs) such as derivatives and repurchase agreements, particularly those held by systemically important major dealer banks. Under current U.S. bankruptcy law, these contracts are exempted from the automatic stay. The advantages and disadvantages of this treatment have been a matter of significant debate for the past decade, particularly since the 2008 crisis. After some background on QFCs and automatic stays, we provide our joint analysis of the costs and benefits of stays on the QFCs, with a focus on systemically important financial institutions, including the special case of central market utilities. Following this, we state our respective policy conclusions. Briefly speaking, we both believe that repos (and certain closely related QFCs) that are backed by liquid securities should be exempt from automatic stays, or receive an effectively similar treatment. Repos backed by illiquid assets, on the other hand, should not be given this safe harbor. We both believe that derivatives that have not been centrally cleared should be subject to automatic stays. One of us believes that stays should also apply to cleared derivatives. The other author favors an exemption of cleared derivatives from stays, except in the case of a failure of a regulated central clearing party.

Prior to the enactment of the Dodd-Frank Act last summer, derivatives and repurchase agreements (“repos”) were largely unregulated outside of bankruptcy, and also were exempted from core bankruptcy provisions such as the automatic stay, which prevents creditors from seizing collateral or attempting to collect what they are owed. The Dodd-Frank Act now extensively regulates derivatives outside of bankruptcy, but it left their special treatment in bankruptcy completely untouched. There is a gap in the debate over this special treatment. To date, neither scholars nor the derivatives industry have fully analyzed the key counterfactual: what would happen if derivatives and repos were subject to the same treatment as other contracts? This Article tries to fill the gap, and to develop a more general theory about the importance of “transaction consistency” in the bankruptcy laws. Our findings are surprising. Contrary to the dire warnings of the repo industry, the effect of transaction consistency on repos would be limited, because repos would automatically be terminated as of the bankruptcy filing and thus could not be reinstated by the debtor. Derivatives have more at stake, but the nondebtor’s right of setoff would reduce many of the adverse effects. We do not argue that the special treatment should simply be removed, however. Given the distinctive attributes of these contracts, we argue that repo lenders should be able to immediately sell some kinds of collateral and that the automatic stay should be limited to three days for derivatives. We also explain how transaction consistency can be integrated with the Dodd-Frank Act. We believe that that the reforms we propose would strongly enhance bankruptcy’s efficacy, and make Dodd-Frank resolution unnecessary in all but the most extraordinary cases.

PURPOSE We studied oncologists' attitudes and behavior with regard to their participation in randomized clinical trials. METHODS We surveyed the 1,737 physician members of the Eastern Cooperative Oncology Group (ECOG) using the Physician Orientation Profile (POP), a self-administered mailed questionnaire. A response rate of 86% was achieved (1,485 of 1,737); each physician's actual patient accrual was recorded. RESULTS All respondents indicated that they had a systematic pattern of patient preselection for entry onto trials beyond the formal inclusion/exclusion trial criteria. Eighty-nine percent stated that improving patient quality of life rather than prolonging survival was more personally satisfying. Sixty-two percent did not enter a single patient during the 12-month period following the survey, while 10% entered 80% of all patients during that time. Physicians overestimated their accrual rate by a factor of 6. Eighty-three percent defined randomization and adherence to trial protocol as a serious challenge to their ability to make individualized treatment decisions. CONCLUSION This study raises questions regarding the following: (1) the perceived generalizability of trial findings, (2) the role of end points other than survival for clinical trials, (3) the consequences of physician overestimation of patient accrual, and (4) the impact of randomized trials on the behavior of clinicians. Further investigation into these critical issues will provide meaningful recommendations to enhance the future design, implementation, and conduct of randomized clinical trials in cancer.

BACKGROUND Studies have shown that response to a given chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer is superior to that in patients previously treated with other regimens. This finding raises the question of whether it is necessary and ethical to study the effects of new anticancer agents in untreated patients. Such studies appear to be the best test for drug development, but there has been no evaluation of whether survival of untreated patients, whose cancer is sensitive to established drugs, is adversely affected in trials of new drugs. PURPOSE This randomized study of untreated patients with extensive-stage small-cell lung cancer was designed (a) to compare the survival of patients treated with either effective standard chemotherapy or an investigational anticancer drug as initial therapy and (b) to evaluate response rates and toxic effects of such therapies. METHODS Eighty-six patients were randomly assigned to receive, as initial therapy, either the standard CAV regimen--cyclophosphamide (1000 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2) every 3 weeks--or the phase II drug menogaril (200 mg/m2) every 4 weeks. Treatment after induction therapy varied, depending on patient response, but nonresponders and those with disease progression received salvage chemotherapy--etoposide (120 mg/m2 on days 1, 2, and 3) and cisplatin (60 mg/m2 on day 1), repeated every 3 weeks. RESULTS Of the 43 patients on CAV, 42% responded (eight complete responses and 10 partial responses); 5% of the 43 on menogaril responded (two partial responses) (P = .0001). Twelve (22%) of 54 patients responded to salvage chemotherapy (five complete responses and seven partial responses). Within 3 months from start of treatment, twelve patients died--3 patients in the CAV group and nine patients in the menogaril group (P = .12). The estimated median survival was 37 weeks with menogaril and 45 weeks with CAV (P = .28). At 6 months, survival was 76.7% for the CAV group and 67.4% for the menogaril group. At 12 months, survival rates were 24.4% and 27.9%, respectively. Confidence intervals (95%) for the differences between the proportions surviving in the two groups were -9%-28% at 6 months and -25%-14% at 12 months. Use of CAV resulted in significantly higher occurrence of severe and life-threatening treatment-related complications (P = .002). CONCLUSION The confidence intervals for the differences in survival are too wide to conclude that evaluation of a new drug in untreated patients with extensive-stage small-cell lung cancer is or is not harmful. The data do suggest, however, that use of this study design may have no adverse effect on survival.

Ten patients with unresectable liver metastases from intraabdominal primary malignancies were treated with combined hepatic irradiation and hepatic artery infusion with FUdR using an Infusaid pump. The median survival for the entire group was 10 months. Four (40%) demonstrated an objective response to treatment: Three patients had a decrease in tumor mass on computed tomography (CT) scan, and one patient had a reduction in liver size as measured by palpation. The survival of two of the three patients whose tumor size was observed to be reduced on CT scan was significantly longer than that of the rest of the group (23, 37, and 12 months). Treatment was generally well tolerated with only mild side effects. Morbidity from chemotherapy did not appear to be enhanced by combination with hepatic irradiation. This form of treatment, although it has not demonstrated improved survival compared with other treatments in this setting, may be considered for adjuvant therapy in patients with hepatic metastases.

The history of the numerical solution of ordinary differential equations is surveyed from its origins three centuries ago up to the early 1970s. The increasing demands for the solution of ODEs, especially for exterior ballistics and celestial mechanics, has been a primary stimulus of and a significant influence on the early development of computers starting with the analog differential analyzers and continuing to the first wired-program digital computers—whose form foreshadowed future developments in parallel computers. At the same time the hardware has, of course, affected the algorithms used, but this has resulted in surprisingly few innovations in numerical techniques.

A case of hepatic adenoma imaged by magnetic resonance imaging (MRI) as well as with angiography, computed tomography, and radionuclide imaging is presented. Pathological correlation is also presented. Review of the literature of MRI of hepatic adenoma and related tumors is discussed.

There have been no published performance evaluations of nongovernmental, voluntary habitat stewardship programs. The Operation Burrowing Owl (OBO) stewardship program, initiated in 1987, was evaluated for its effectiveness in conservation of grassland habitat during 1986-1993. The 108 OBO sites from 1987 to 88 and 98 randomly selected non-OBO sites that were grassland in 1986 in the Regina-Weyburn, Saskatchewan study area were classified by size and agricultural soil suitability. By 1993, 41 (38%) of the 108 OBO sites had been withdrawn from the program. The 1986 area of grassland was compared with grassland area calculated from digitized 1993 LANDSAT imagery. A correction for satellite inaccuracies was determined. Grassland retention in 1993 was significantly higher at OBO sites (66%) than at random sites (49%), demonstrating that the OBO voluntary program effectively conserved habitat. Also, grassland retention was significantly lower on sites with better agricultural soils, and for sites

Although injection drug use accounts for only 5% to 10% of cumulative HIV infections globally, it is a more efficient way of spreading HIV than sexual intercourse. HIV epidemics among injection drug users (IDUs) have a potential for rapid spread of the virus within the IDU community and outward into the general population. Effective interventions addressing this mode of HIV transmission are needed because part of a comprehensive strategy to curb the spread of HIV infection. IDUs, often marginalized, pose serious health challenges that can no longer be overlooked. Health care providers need to familiarize themselves with these challenges in order to meet the needs of this disenfranchised population. Providers need to have a clear understanding of targeted behavior and their patients' environmental context. Efforts must be made to foster healthy behavior among IDUs to assist them in managing their infection effectively and become productive members of society. This paper reviews these challenges and outlines selected models that may assist health care providers in fostering behavior changes among HIV-positive injection drug users.

We analyze a sample of large Chapter 11 cases to determine which factors motivate the choice of filing in one court over another when a choice is available. We focus in particular on the Delaware court, which became the most popular venue for large corporations in the 1990s. We find no evidence to suggest that Delaware's popularity was driven by managers or equity holders seeking a procedure friendly to their interests. Instead, debt structure differences, specifically, the fraction of assets financed with secured debt, and court characteristics, particularly a court's level of experience, are the most important factors driving the choice of venue. While Delaware does not appear significantly different with respect to deviations from absolute priority in favor of equity or likelihood of producing reorganizations, it does differ along the dimension of speed. Controlling for other factors, we find that a Delaware reorganization is between 140 and 190 days faster than an equivalent case in another court. Given that speed benefits secured creditors most, we conclude that Delaware's popularity in the 1990s was unlikely to have resulted from a pro-debtor bias combined with a manager or equity holder preference for Delaware.

Despite reports that i.v. melphalan is active in the settings of conditioning regimens utilizing high-dose chemotherapy for autologous bone marrow transplantation and in isolated limb perfusion for the treatment of malignant melanoma, its activity at conventional doses has never been defined in this disease. We conducted a phase II study of conventional-dose i.v. melphalan (30 mg/m2) in 17 patients with metastatic melanoma. All patients were previously untreated with chemotherapy with performance status 0, 1 or 2. Forty-seven cycles were given with a median of two cycles. One patient was not evaluable due to early death. There were no responses in the 16 patients, resulting in a 0% response rate (95% confidence interval = 0-17%). We conclude that conventional-dose melphalan by i.v. administration has no appreciable activity in patients with metastatic malignant melanoma.

Background: Pseudomyxoma peritonei, a tumor which spreads chiefly along peritoneal surfaces, has recently been treated by resection followed by intraperitoneal infusion of 5-fluorouracil (5-FU). Reports on the cardiotoxicity of this drug, given intravenously, indicate an incidence of 1.4–2.9%. Although several deaths have been reported following 5-FU therapy by continuous intravenous infusion, none has apparently been reported following bolus intravenous injection. Method: Radical resection of an extensive pseudomyxoma peritonei was performed. Following convalescence, intraperitoneal infusion of 5-FU was initiated in a daily dose of 20 mg/kg body weight (1,440 mg), planned for administration in multiple 5-day cycles. Results: After three uneventful daily infusions of 5-FU, the patient suddenly died, apparently of a sudden cardiac event. Autopsy provided no explanation for his death. The coronary arteries were free of disease and no residual tumor was found. A review of the literature reveals no report of a cardiac death from 5-FU following its intraperitoneal administration. Conclusions: The fatality suggests the potential toxicity of 5- FU when administered intraperitoneally, a factor to be considered in decisions to use this drug intraperitoneally.

This article addresses the question whether the recent changes in bank and insurance firm governance suggest that U.S. financial firm governance will soon replicate the governance of nonfinancial firms. In addressing this question, the Article starts from the assumption that we must consider both corporate governance and the background insolvency procedures to fully appreciate the overall governance framework. In particular, the relationship between corporate governance and insolvency tends to be complementary. The governance of nonfinancial U.S. firms, for instance, relies on ex post correctives such as takeovers to address the conflicts of interest between managers and widely scattered shareholders; and if the firm fails, offers a manager-driven reorganization option. In other nations, such as Germany and Japan, banks and other large investors actively participate in corporate governance; bankruptcy is characterized by immediate displacement of managers and liquidation of the firm. I describe U.S. governance as an "ex post" framework, and the German and Japanese alternative as an "ex ante" approach. Unlike nonfinancial firms, the governance of U.S. banks and insurance companies has long been ex ante in character. Takeovers and other ex post correctives have been rare, and insolvency means immediate removal of the managers and liquidation of the firm. Although the principal overseer of bank and insurance managers is a governmental regulator, rather than a private investor, the overall governance framework functions very much like the approach used by nonfinancial firms in Germany and Japan. The recent changes in bank and insurance firm governance have introduced a significantly greater market component, but the regulatory framework puts real limits on how far the transition can or will go. Despite the changes, bank and insurance governance has retained much of its traditional character. As the discussion thus far suggests, much of the analysis is descriptive rather than normative in character. In discussing the treatment of insolvent banks and insurers, however, the article offers several prescriptions for improving the governance framework. In order to reduce managers' current incentive to avoid insolvency proceedings at all costs, and to harness managers' superior information about the firm, the article calls for changes to both bank and insurance insolvency law. In banking, managers should be permitted to propose a "prepackaged" purchase and assumption transferring the banks assets and liabilities to another bank; and a traditional reorganization option should be added to insurance insolvency. The article also argues that lawmakers should add insurance insolvency (though not bank insolvency) to the Bankruptcy Code.

Author(s): Moinpour, CM; Savage, MJ; Troxel, A; Lovato, LC; Eisenberger, M; Veith, RW; Higgins, B; Skeel, R; Yee, M; Blumenstein, BA; Crawford, ED; Meyskens, FL | Abstract: BackgroundFor patients with metastatic prostate cancer, treatment is primarily palliative, relying mainly on the suppression of systemic androgen hormone levels. To help document the achievement of palliation and to characterize positive and negative effects of treatment, we evaluated quality-of-life (QOL) parameters in patients with metastatic prostate cancer who were randomly assigned to two methods of androgen deprivation.MethodsPatients (n = 739) with stage M1 (bone or soft tissue metastasis) prostate cancer were enrolled in a QOL protocol that was a companion to Southwest Oncology Group INT-0105, a randomized double-blind trial comparing treatment with bilateral orchiectomy (surgical castration) plus either flutamide or placebo. Patients completed a comprehensive battery of QOL questionnaires at random assignment to treatment and at 1, 3, and 6 months later. Data were collected on three treatment-specific symptoms (diarrhea, gas pain, and body image), on physical functioning, and on emotional functioning. All P values are two-sided.ResultsQuestionnaire return rates for this study never dropped below 80%; only 2% of the patients did not submit baseline QOL assessments. Cross-sectional analyses (corrected for multiple testing) identified statistically significant differences that favored orchiectomy plus placebo for two of the five primary QOL parameters as follows: patients receiving flutamide reported more diarrhea at 3 months (P = .001) and worse emotional functioning at 3 and 6 months (both Pl.003). Longitudinal analyses replicated these findings. Other analyzed QOL parameters favored the group receiving placebo but were not statistically significant after adjustment for multiple testing.ConclusionsWe found a consistent pattern of better QOL outcomes at each follow-up assessment during the first 6 months of treatment for orchiectomized patients with metastatic prostate cancer who received placebo versus flutamide. Improvement over time was evident in both treatment groups but more so for patients receiving placebo.

Carcinogenesis is a stepwise process that occurs through mutations of cancer-related genes. Five or more genes must be mutated before malignant transformation occurs in most adult cancers; in some childhood cancers as few as two mutated genes may be sufficient. A rare inherited mutation of a critical gene may predestine cancer to occur in one or more sites. This germline mutation is present in virtually every cell in the body, except half of the germ cells, which do not contain the mutated gene in their haploid chromosome set. These and other genes have been used to piece together a puzzle of regulatory systems that govern cell division and proliferation, as well as apoptosis or programmed cell death. Mutations of these genes result not only in increased cell proliferation but also in diminished cell death. Most genetic changes that occur during carcinogenesis are not inherited or germline. They are acquired after birth and are called somatic mutations. A somatic mutation affects only the mutated cell and its progeny. Each time a cell divides, there is a chance of somatic mutation, and therefore there always is a low, background risk for cancer and other malignant lesions. A far more prevalent cause of cancer-related death in the United States is environmental exposure. Such exposure causes somatic mutations of cancer-related genes through direct damage to DNA or through alteration of proliferation or cell death, which enhances the baseline risk for mutation. As carcinogenesis becomes understood, interventions may be designed that selectively interfere in important steps. Screening for cancer is based on the premise that one can treat a patient for a cancer that has not spread from its primary site. Nevertheless, cancer screening is controversial and often confusing. Issues of costs, risks versus benefits, physical time and effort, and patient compliance all affect the clinician's view of screening, often to the extent that the true value of this approach to cancer control is underappreciated and underutilized. A clinician should consider the following questions when assessing the priority, scope, and intensity of cancer screening. Is the cancer an important public health problem? Can preclinical stages be detected and cured? Are effective screening tests available? Are the tests feasible and acceptable? Have screening programs reduced cancer-specific mortality? Is the screening program cost effective? Is screening generally recommended? There is clear-cut evidence of benefit from screening for cancer of the cervix, breast, colon and rectum, and skin and some specific genetic syndromes. Evidence of survival benefit from screening for prostate cancer is lacking, although prostate specific antigen screening is widely used. Screening for lung and ovarian cancer is ineffective.

e14098 Background: Neuropilin 2 (NRP2) is a transmembrane glycoprotein, non-associated with kinase domains, implicated in neovascularization and metastasis of colon cancer. NRP2 has been proposed as a molecular marker for targeted cancer therapy based on its multiple functions in cancer promotion. NRP2 signaling pathway and its expression have been demonstrated in many carcinomas. To the best of our knowledge, no description of the immunohistochemical staining pattern of NRP2 in colon cancer has been published in the English medical literature. The aim of this study is to investigate the NRP2 labelilng pattern in colon cancer and correlate it with tumor stage. Methods: Tumor sections from 35 randomly selected colectomy specimens with colorectal cancer collected during the last three years were retrieved from the University of Toledo Medical Center Department of Pathology archival material. Formalin fixed, paraffin embedded, 4 μm tissue sections containing invasive tumor were immunolabeled with a commercial antibody against NRP2, using a Ventana Benchmark LT automated instrument. Randomized, immunolabeled colon cancer tissue sections were blindly reviewed by two pathologists. Cytoplasmic and nuclear expression of NRP2 by tumor cells was graded as negative (no staining), focal (staining in

Ancrod is a rapid-acting defibrinogenating agent derived from the venom of the Malayan pit viper which has been used successfully as an alternative to heparin sulfate for anticoagulation during peripheral vascular procedures and coronary artery bypass surgery. We describe the first use of ancrod for anticoagulation before and during percutaneous transluminal coronary angioplasty (PTCA) in a patient with heparin-associated thrombocytopenia. © 1994 Wiley-Liss,Inc..