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Rules help guide our behavior-particularly in complex social contexts. But rules sometimes give us the "wrong" answer. How do we know when it is okay to break the rules? In this paper, we argue that we sometimes use contractualist (agreement-based) mechanisms to determine when a rule can be broken. Our model draws on a theory of social interactions - "virtual bargaining" - that assumes that actors engage in a simulated bargaining process when navigating the social world. We present experimental data which suggests that rule-breaking decisions are sometimes driven by virtual bargaining and show that these data cannot be explained by more traditional rule-based or outcome-based approaches., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: Serious illness conversations help clinicians align medical decisions with patients' goals, values, and priorities and are considered an essential component of shared decision-making. Yet geriatricians at our institution have expressed reluctance about the serious illness care program., Objectives: We sought to explore geriatricians' perspectives on serious illness conversations., Methods: We conducted focus groups with interprofessional stakeholders in geriatrics., Results: Three key themes emerged that help explain the reluctance of clinicians caring for older patients to have or document serious illness conversations: 1) aging in itself is not a serious illness; 2) geriatricians often focus on positive adaptation and social determinants of health and in this context, the label of "serious illness conversations" is perceived as limiting; and 3) because aging is not synonymous with illness, important goals-of-care conversations are not necessarily documented as serious illness conversations until an acute illness presents itself., Conclusion: As institutions work to create system-wide processes for documenting conversations about patients' goals and values, the unique communication preferences of older patients and geriatricians should be specifically considered., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Understanding the frequency of non-additive effects of pesticides (synergism and antagonism) is important in the context of risk assessment. The goal of this study was to investigate the prevalence of non-additive effects of pesticides to honey bees (Apis mellifera). We investigated a large set of mixtures including insecticides and fungicides of different chemical modes of action and classes. The mixtures included represent a relevant sample of pesticides that are currently used globally. We investigated whether the experimental toxicity of the mixtures could be predicted based on the Concentration Addition (CA) model for acute contact and oral adult bee toxicity tests. We measured the degree of deviation from the additivity predictions of the experimental toxicity based on the well-known Mixture Deviation Ratio (MDR). Further, we investigated the appropriate MDR thresholds that should be used for the identification of non-additive effects based on acceptable rates for false positive (alpha) and true positive (beta) findings. We found that a deviation factor of MDR = 5 is a sound reference for labeling potential non-additive effects in acute adult bee experimental designs when assuming a typical Coefficient of Variation (CV%) = 100 in the determination of the LD 50 of a pesticide (a factor of 2× deviation in the LD 50 resulting from inter-experimental variability). We found that only 2.4 % and 9 % of the mixtures evaluated had an MDR > 5 and MDR < 0.2, respectively. The frequency and magnitude of deviation from additivity found for bees in this study are consistent with those of other terrestrial and aquatic taxa. Our findings suggest that additivity is a good baseline for predicting the toxicity of pesticide mixtures to bees, and that the rare cases of synergy of pesticide mixtures to bees are not random but have a mechanistic basis., Competing Interests: Declaration of competing interest The authors are employees of Bayer Crop Science, a manufacturer of crop protection products., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Air pollution exposure is ubiquitous with demonstrated effects on morbidity and mortality. A growing literature suggests that prenatal air pollution exposure impacts neurodevelopment. We posit that the Environmental influences on Child Health Outcomes (ECHO) program will provide unique opportunities to fill critical knowledge gaps given the wide spatial and temporal variability of ECHO participants., Objectives: We briefly describe current methods for air pollution exposure assessment, summarize existing studies of air pollution and neurodevelopment, and synthesize this information as a basis for recommendations, or a blueprint, for evaluating air pollution effects on neurodevelopmental outcomes in ECHO., Methods: We review peer-reviewed literature on prenatal air pollution exposure and neurodevelopmental outcomes, including autism spectrum disorder, attention deficit hyperactivity disorder, intelligence, general cognition, mood, and imaging measures. ECHO meta-data were compiled and evaluated to assess frequency of neurodevelopmental assessments and prenatal and infancy residential address locations. Cohort recruitment locations and enrollment years were summarized to examine potential spatial and temporal variation present in ECHO., Discussion: While the literature provides compelling evidence that prenatal air pollution affects neurodevelopment, limitations in spatial and temporal exposure variation exist for current published studies. As >90% of the ECHO cohorts have collected a prenatal or infancy address, application of advanced geographic information systems-based models for common air pollutant exposures may be ideal to address limitations of published research., Conclusions: In ECHO we have the opportunity to pioneer unifying exposure assessment and evaluate effects across multiple periods of development and neurodevelopmental outcomes, setting the standard for evaluation of prenatal air pollution exposures with the goal of improving children's health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

An outbreak of SARS-CoV-2 in a skilled nursing facility (SNF) can be devastating for residents and staff. Difficulty identifying asymptomatic and presymptomatic cases and lack of vaccination or treatment options make management challenging. We created, implemented, and now present a guide to rapidly deploy point-prevalence testing and 3-tiered cohorting in an SNF to mitigate an outbreak. We outline key challenges to SNF cohorting., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Context: The disparity between gaps in workforce and availability of palliative care (PC) services is an increasing issue in health care. To meet the demand, team-based PC requires additional educational training for all clinicians caring for persons with serious illness., Objectives: To describe the educational methodology and evaluation of an existing regional interdisciplinary PC training program that was expanded to include chaplain and social worker trainees., Methods: From 2015 to 2017, 26 social workers, chaplains, physicians, nurses, and advanced practice providers representing 22 health systems completed a two-year training program. The curriculum comprises biannual interdisciplinary conferences, individualized mentoring and clinical shadowing, self-directed e-learning, and profession-focused seminar series for social workers and chaplains. Site-specific practice improvement projects were developed to address gaps in PC at participating sites., Results: PC and program development skills were self-assessed before and after training. Among 12 skills common to all disciplines, trainees reported significant increases in confidence across all 12 skills and significant increases in frequency of performing 11 of 12 skills. Qualitative evaluation identified a myriad of program strengths and challenges regarding the educational format, mentoring, and networking across disciplines., Conclusion: Teaching PC and program development knowledge and skills to an interdisciplinary regional cohort of practicing clinicians yielded improvements in clinical skills, implementation of practice change projects, and a sense of belonging to a supportive professional network., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hydatid cysts are caused by Echinococcus granulosus infection, and hydatidosis is recognized as a re-emerging zoonotic disease globally. While the liver is the most commonly affected organ, other organs can also be affected, including the heart. Because of the low sensitivity and specificity of serologic diagnostic tests, ultrasound and echocardiography are increasingly used to make the diagnosis of cardiac hydatid cyst., Case Report: We report the case of a cardiac hydatid cyst, detected by point-of-care ultrasound (POCUS), in a 79-year-old woman who presented with shortness of breath and was in ventricular tachycardia. The diagnosis was further confirmed with a computed tomography scan. Although cases of alveolar and liver hydatid cysts are seen, this is the first case of a cardiac hydatid cyst in Bhutan. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case illustrates the importance of POCUS in reaching a diagnosis, particularly in resource-poor areas where other sophisticated diagnostic tools are not easily available. A cardiac hydatid cyst must be in the differential for structural causes of dysrhythmias. This is especially so because treatment of unstable dysrhythmias in the acute setting of an emergency department has to be modified from the usual algorithm in the presence of a cardiac hydatid cyst, due to the potentially fatal risk of cyst rupture and anaphylaxis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The health implications of urban development, particularly in rapidly changing, low-income urban neighborhoods, are poorly understood. We describe the Healthy Neighborhoods Study (HNS), a Participatory Action Research study examining the relationship between neighborhood change and population health in nine Massachusetts neighborhoods. Baseline data from the HNS survey show that social factors, specifically income insecurity, food insecurity, social support, experiencing discrimination, expecting to move, connectedness to the neighborhood, and local housing construction that participants believed would improve their lives, identified by a network of 45 Resident Researchers exhibited robust associations with self-rated and mental health. Resident-derived insights into relationships between neighborhoods and health may provide a powerful mechanism for residents to drive change in their communities., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: The rapid increase in demand for palliative care (PC) services has led to concerns regarding workforce shortages and threats to the resiliency of PC teams., Objectives: To describe the development, implementation, and evaluation of a regional interdisciplinary training program in PC., Methods: Thirty nurse and physician fellows representing 22 health systems across the Chicago region participated in a two-year PC training program. The curriculum was delivered through multiple conferences, self-directed e-learning, and individualized mentoring by expert local faculty (mentors). Fellows shadowed mentors' clinical practices and received guidance on designing, implementing, and evaluating a practice improvement project to address gaps in PC at their institutions., Results: Enduring, interdisciplinary relationships were built at all levels across health care organizations. Fellows made significant increases in knowledge and self-reported confidence in adult and pediatric PC and program development skills and frequency performing these skills. Fellows and mentors reported high satisfaction with the educational program., Conclusion: This interdisciplinary PC training model addressed local workforce issues by increasing the number of clinicians capable of providing PC. Unique features include individualized longitudinal mentoring, interdisciplinary education, on-site project implementation, and local network building. Future research will address the impact of the addition of social work and chaplain trainees to the program., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Evidence suggests that dental emergencies are likely to occur when preferred care is less accessible. Communication barriers often exist that cause patients to receive suboptimal treatment or experience discomfort for extended lengths of time. Furthermore, limitations in the conventional approach for managing dental emergencies prevent dentists from receiving critical information before patient visits., Methods: The authors developed a mobile application to mediate the uncertainty of dental emergencies. The development and study consisted of a needs analysis and quality assessment of intraoral images captured by smartphones, prototype development, refining the prototype through usability inspection methods, and formative evaluation through usability testing with prospective users., Results: The developed application successfully guided all users through a series of questions designed to capture clinically meaningful data by using familiar smartphone functions. All participants were able to complete a report within 4 minutes, and all clinical information was comprehended by the users., Conclusions: Patient-provided information accompanied by high-resolution images may help dentists substantially in predicting urgency or preparing necessary treatment resources. The results illustrate the feasibility of patients using smartphone applications to report dental emergencies. This technology allows dentists to assess care remotely when direct patient contact is less practical., Practical Implications: This study's results demonstrate that patients can use mobile applications to transmit clinical data to their dentists and suggest the possibility of expanding the use of mobile applications to enhance access to routine and emergency dental care. The authors addressed how to enable patients to communicate emergency needs directly to a dentist while obviating patient emergency department visits., (Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.)

CD163 is a macrophage scavenger receptor with anti-inflammatory and pro-inflammatory functions. Here, we report that alveolar macrophages (AMΦs) from asthmatic subjects had reduced cell-surface expression of CD163, which suggested that CD163 might modulate the pathogenesis of asthma. Consistent with this, house dust mite (HDM)-challenged Cd163(-/-) mice displayed increases in airway eosinophils and mucous cell metaplasia (MCM). The increased airway eosinophils and MCM in HDM-challenged Cd163(-/-) mice were mediated by augmented CCL24 production and could be reversed by administration of a neutralizing anti-CCL24 antibody. A proteomic analysis identified the calcium-dependent binding of CD163 to Dermatophagoides pteronyssinus peptidase 1 (Der p1). Der p1-challenged Cd163(-/-) mice had the same phenotype as HDM-challenged Cd163(-/-) mice with increases in airway eosinophils, MCM and CCL24 production, while Der p1 induced CCL24 secretion by bone marrow-derived macrophages (BMMΦs) from Cd163(-/-) mice, but not BMMΦs from wild-type (WT) mice. Finally, airway eosinophils and bronchoalveolar lavage fluid CCL24 levels were increased in Der p1-challenged WT mice that received adoptively transferred AMΦ's from Cd163(-/-) mice. Thus, we have identified CD163 as a macrophage receptor that binds Der p1. Furthermore, we have shown that HDM-challenged Cd163(-/-) mice have increased eosinophilic airway inflammation and MCM that are mediated by a CCL24-dependent mechanism.

Most deaths in the United States are preventable and related to nutrition. Although physicians are expected to counsel their patients about nutrition-related health conditions, a recent survey reported minimal improvements in nutrition medicine education in US medical schools in the past decade. Starting in 2006, we have developed an educational plan using a novel student-centered model of nutrition medicine education at Boston University School of Medicine that focuses on medical student-mentored extracurricular activities to develop, evaluate, and sustain nutrition medicine education. The medical school uses a team-based approach focusing on case-based learning in the classroom, practice-based learning in the clinical setting, extracurricular activities, and a virtual curriculum to improve medical students' knowledge, attitudes, and practice skills across their 4-y period of training. We have been using objectives from the NIH National Academy Awards guide and tools from the Association of American Medical Colleges to detect new areas of nutrition medicine taught at the medical school. Although we were only able to identify 20.5 h of teaching in the preclerkship years, we observed that most preclerkship nutrition medicine objectives were covered during the course of the 4-y teaching period, and extracurricular activities provided new opportunities for student leadership and partnership with other health professionals. These observations are very encouraging as new assessment tools are being developed. Future plans include further evaluation and dissemination of lessons learned using this model to improve public health wellness with support from academia, government, industry, and foundations.

Background: Ventricular assist devices (VAD) are associated with the formation of antibodies to anti-human leukocyte antigens (HLA) or sensitization. The incidence and effects of VAD-associated anti-HLA sensitization have not been well studied in the pediatric population., Methods: A retrospective review of all patients undergoing VAD implant at our institution from 1998 to 2008 was performed. Panel reactive antibody (PRA) results before VAD implant, after VAD implant, and after orthotopic heart transplantation (OHT) were recorded. Patients who became sensitized (PRA for class I and/or II immunoglobulin G antibodies >or= 10%) on VAD support were compared with non-sensitized patients with regard to demographics, diagnosis, device type, and blood product exposure on VAD support. Outcomes after OHT were also compared between groups., Results: VAD support was initiated in 20 patients (median age, 14.4 years), with 75% survival to OHT or recovery. PRA data before and after VAD implant were available for 17 patients. VAD-associated sensitization developed in 35% of recipients. There were no differences between those sensitized in association with VAD support and non-sensitized patients with regard to age, gender, diagnosis, device type, extracorporeal membrane oxygenation use, or blood product exposure on VAD support. Black race predicted sensitization on VAD (p = 0.02). There were no differences in survival or rejection between groups., Conclusions: VAD therapy was associated with the development of anti-HLA sensitization in 35% of recipients. Black race predicted sensitization, but there were no differences in overall survival or outcomes after OHT., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole.

Down's syndrome (DS) in humans is caused by trisomy of chromosome 21 (HSA 21). DS patients have a variety of pathologies, including mental retardation and an unusually high incidence of leukemia or lymphoma such as megakaryocytic leukemia. Individuals with DS develop the characteristic neuropathological hallmarks of Alzheimer's disease (AD) in early adulthood, generally by the fourth decade of life. There are several mouse models of DS that have a segmental trisomy of mouse chromosome 16 (MMU 16) with triplicated genes orthologous to HSA 21. These mice display neurodegeneration similar to DS. Although brain pathology in DS models is known, little information is available about other organs. We studied the extraneural pathology in aged DS mice (Ts65Dn, Ts2 and Ts1Cje aged 8 to 24 months) as well as other mouse models of neurodegeneration, including presenilin (PS), amyloid-beta precursor protein (APP), and tau (hTau and JNPL) transgenic mice. An increased incidence of peripheral amyloidosis, positive for amyloid A (AA) but not amyloid-beta peptide (A beta), was found in APP over-expressing and tauopathic mice as compared to non-transgenic (ntg) littermates or to DS mouse models. A higher incidence of lymphoma was found in the DS models, including Ts1Cje that is trisomic for a small segment of MMU 16 not including the App gene, but not in the APP over-expressing mice, suggesting that high APP expression is not the cause of lymphoma in DS. The occurrence of lymphomas in mouse DS models is of interest in relation to the increased incidence of malignant conditions in human DS.

The four choroid plexuses in the brain ventricles are not identical, but differences among them have rarely been studied. The present work concerns the inflammatory and hemorrhagic choroid plexitis produced in Lewis rats by a single gavage of cholecalciferol (vitamin D(3)) or related steroids with vitamin D activity. Plexitis was very severe in the fourth ventricular plexus, somewhat less severe in the lateral ventricular plexuses, and almost absent in the third ventricular plexus. These findings were compared to the scanty data from the literature on differences among the plexuses.

Tyloxapol (Triton WR 1339) is a non-ionic detergent that inhibits lipoprotein lipase and thereby raises levels of serum lipids. It is used frequently for acute studies on lipids in rats but not for subacute or chronic studies. In the present work, we found that tyloxapol must be injected intravenously three times each week in order to have high and sustained levels of serum cholesterol and triglycerides for 1, 2, or 3 weeks. These results make it possible to extend the use of tyloxapol into chronic studies of hyperlipemia and vascular disease.

Thrombolytic therapy remains the most commonly administered revascularization strategy for patients with ST-elevation myocardial infarctions (STEMI). However, many patients fail to have patent arteries or ST-segment resolution after these therapies. Multiple strategies have been examined to treat these patients with "failed thrombolysis." We examined the existing medical literature regarding treatment of failed thrombolysis including strategies testing repeat thrombolytic therapy and rescue percutaneous coronary intervention. Additional, we reviewed the literature regarding the efficacy of transferring patient for rescue percutaneous intervention and coronary stenting. The impact of contemporary antiplatelet strategies, cardiogenic shock, and coronary bypass surgery was examined. Overall, the management of patients with acute STEMI in whom thrombolytic therapy failed remains a challenging problem. As a result, many different strategies are currently in use. Among these therapeutic interventions, rescue PCI with coronary stenting appears to be superior when it is done in a timely manner by an experienced center.

Background: Accurate surveillance for pneumonia requires standardized classification of chest radiographs. Digital imaging permits rapid electronic transfer of data to radiologists, and recent improvements in digital camera technology present high quality, yet cheaper, options., Methods: We evaluated the comparative utility of digital camera versus film digitizer in capturing chest radiographs in a pneumonia surveillance system in rural Thailand using a panel of radiologists; the gold standard was the hard-copy radiograph. We calculated sensitivity and specificity and conducted a receiver operator characteristics (ROC) analysis., Results: Of the 192 radiographs from patients with clinical pneumonia, 166 (86%) were classified as pneumonia on the hard copies. Sensitivity and specificity for identifying pneumonia were 89% and 73% for the camera and 90% and 65% for the digitizer. In the ROC analysis, there was no statistically significant difference in the area under the curve (camera, 0.86; film digitizer, 0.91, p = 0.29). The digital camera set cost 965 dollars compared to 3000 dollars for the film digitizer., Conclusion: Detection of pneumonia was not measurably compromised by using digital cameras compared with film digitizers. The 3-fold lower cost of the digital camera makes this technology an affordable and widely accessible alternative for surveillance systems, vaccine trials, and perhaps clinical use.

We observed hydropic degeneration of the anterior pituitary in rats made uremic by nephrotoxic chemicals, especially when the uremic rats were given a pure carbohydrate diet beforehand. The hydropic degeneration caused loss of nuclear and cytoplasmic content of many or most anterior pituitary cells. It was readily visible in paraffin sections by light microscopy. It was exaggerated when water was injected after the nephrotoxin and it was greatly reduced if saline was injected after the nephrotoxin. Low serum sodium levels in affected rats and the response to saline injection suggested that the mechanism for development of hydropic degeneration of the anterior pituitary gland involved hyponatremia. Depletion of total body sodium probably accounts for the enhancement of hydropic degeneration by the pure carbohydrate diet. Morphologic lesions of the anterior pituitary related to hyponatremia and uremia have not been described previously.

This chapter presents a review of brain-computer communication based on motor imagery and the dynamics of brain oscillations. The concept of motor imagery as experimental strategy and the two different modes of operation a brain-computer interface can have are explained. An EEG based brain switch that can control a FES-induced hand grasp of a tetraplegic and an approach towards an ECoG based brain switch are presented.

Severe edema developed around the kidneys of rats after several days of uremia induced by large intravenous doses of mercuric chloride. Edema was prevented when the kidney was removed or had its hilum ligated, or when rats were deprived of fluid intake. The edema fluid had a very low protein content. These facts suggested that the edema was derived from the kidneys, probably from the glomerular filtrate, and that the edema depended on some degree of remaining renal function. Increased permeability of the necrotic proximal tubules and obstruction by casts in the collecting tubules may have been involved. Histologic study suggested that the fluid diffused through the intact renal capsule. These experiments provide a model for perinephric (perirenal) fluid accumulation in certain human diseases and in certain intoxications of grazing animals.

Objective: To study the spatiotemporal pattern of event-related desynchronization (ERD) and event-related synchronization (ERS) in electrocorticographic (ECoG) data with closely spaced electrodes., Methods: Four patients with epilepsy performed self-paced hand movements. The ERD/ERS was quantified and displayed in the form of time-frequency maps., Results: In all subjects, a significant beta ERD with embedded gamma ERS was found., Conclusions: Self-paced movement is accompanied not only by a relatively widespread mu and beta ERD, but also by a more focused gamma ERS in the 60-90 Hz frequency band.

Existing work on the acquisition of syntax has been concerned mainly with the early stages of syntactic development. In the present study we examine later syntactic development in children. Also, existing work has focused on commonalities in the emergence of syntax. Here we explore individual differences among children and their relation to variations in language input. In Study 1 we find substantial individual differences in children's mastery of multiclause sentences and a significant relation between those differences and the proportion of multiclause sentences in parent speech. We also find individual differences in the number of noun phrases in children's utterances and a significant relation between those differences and the number of noun phrases in parent speech. In Study 2 we find greater syntactic growth over a year of preschool in classes where teachers' speech is more syntactically complex. The implications of our findings for the understanding of the sources of syntactic development are discussed.

Acute thrombocytopenia is a recognized complication of treatment with GPIIb/IIIa inhibitors whose cause is not yet known. We studied 9 patients who developed severe thrombocytopenia (platelets less than 25 x 10(9)/L) within several hours of treatment with the GPIIb/IIIa inhibitors tirofiban (4 patients) and eptifibatide (5 patients). In each patient, acute-phase serum contained a high titer (range, 1:80-1:20 000) IgG antibody that reacted with the glycoprotein IIb/IIIa complex only in the presence of the drug used in treatment. Four patients had been previously treated with the same drug, but 5 had no known prior exposure. Pretreatment serum samples from 2 of the latter patients contained drug-dependent antibodies similar to those identified after treatment. No tirofiban- or eptifibatide-dependent antibodies were found in any of 100 randomly selected healthy blood donors, and only 2 of 23 patients receiving tirofiban or eptifibatide who did not experience significant thrombocytopenia had extremely weak (titer, 1:2) tirofiban-dependent antibodies. In preliminary studies, evidence was obtained that the 9 antibodies recognize multiple target epitopes on GPIIb/IIIa complexed with the inhibitor to which the patient was sensitive, indicating that they cannot all be specific for the drug-binding site. The findings indicate that acute thrombocytopenia after the administration of tirofiban or eptifibatide can be caused by drug-dependent antibodies that are "naturally occurring" or are induced by prior exposure to drug. These antibodies may be human analogs of mouse monoclonal antibodies that recognize ligand-induced binding sites (LIBS) induced in the GPIIb/IIIa heterodimer when it reacts with a ligand-mimetic drug.

Study Objectives: The diaphragm adapts to its shortened state in experimental emphysema primarily by losing sarcomeres in series, thus reducing its optimal operating length. One would expect improved diaphragmatic function after lung volume reduction surgery (LVRS) only if the muscle can readapt to its elevated, lengthened postoperative position by either adding back sarcomeres or lengthening sarcomeres. We used a model of elastase-induced emphysema in rats to test the hypothesis that sarcomere addition occurs following LVRS., Design: A cohort of emphysematous rats was created by the intratracheal instillation of elastase. Five months after the instillation, one group of rats underwent measurement of in situ costal diaphragm length via laparotomy, the determination of optimal muscle fiber operating length (Lo) on stimulated diaphragm strips in vitro, and the measurement of sarcomere length by electron microscopy on strips fixed at Lo. Another group of rats underwent LVRS or sham sternotomy 5 months after the instillation, and 5 months following the operation these animals underwent the same series of diaphragmatic studies., Results: Lo was significantly greater in rats that underwent LVRS than those that underwent sternotomy (mean [+/- SE] Lo after LVRS, 2.50 +/- 0.08 cm; mean Lo after sternotomy, 2.27 +/- 0.06 cm; p = 0.013). There was no significant difference in sarcomere lengths between the two groups (2.95 +/- 0.04 vs 3.04 +/- 0.04 microm, respectively; p = 0.10). Using Lo as the length basis, the mean sarcomere number was calculated to be 8,712 +/- 192 in animals that had undergone LVRS and 7,144 +/- 249 in animals that had undergone sternotomy (p < 0.001)., Conclusion: Sarcomere length is not significantly altered but sarcomeres are added in series following LVRS in this experimental model of emphysema/LVRS. It is likely that this sarcomere addition is a prerequisite to the improvement in inspiratory muscle function that has been observed following LVRS in humans.

Objectives: Analysis of event-related desynchronization (ERD) and event-related synchronization (ERS) often requires the investigation of diverse frequency bands. Such analysis can be difficult, especially when using multichannel data. Therefore, an effective method for the visualization of event-related changes in oscillatory brain activity is required., Methods: A bootstrap-based method is presented which gives time-frequency maps showing only significant changes of ERD or ERS in predetermined frequency bands., Results: Examples from an electroencephalographic study and an electrocorticographic study are shown. The results demonstrate how easily reactive channels and their spatio-temporal and frequency-specific characteristics can be identified by means of this method., Conclusions: The proposed method is a simple but effective way to visualize significant ERD/ERS patterns.