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PubMed2001

Genomic tools for gene and protein discovery in malaria: toward new vaccines.

Advances in malaria vaccine and drug development have been hindered in part by the complex multistage life cycle of the parasite, much of which is inaccessible to study, and by a large genome encoding over 5000 genes. Two human models of immunity to malaria, however, suggest that the development of an effective vaccine is within reach. We have outlined a strategy to identify the expression of hundreds to thousands of potential vaccine targets employing recently developed technologies for gene and protein expression. Combined with the exciting developments of malaria DNA vaccine technologies, these approaches form the basis for malaria subunit vaccines that may mimic the protective efficacy of our human model systems and provide the foundation for novel approaches to vaccine development for a range of pathogens.

Animals↗
PubMed2002

[Pneumological diagnostics by means of models aerosols. IV. Clearance of aerosol particles from the pulmonary alveoli. Foundations and first clinical results].

The elimination of deposited particles (inorganic and organic particles, bacteria, viruses) from the periphery of the human lung (alveolar clearance) implies phagocytosis by alveolar macrophages, intracellular digestion, migration and translocation. Alveolar clearance of poorly soluble particles happens very slowly and primarily depends on the function of alveolar macrophages. In humans, the transport of particles to the bronchial tree is of secondary relevance, suggesting that the elimination of particles primarily depends on digestion (dissolution) processes within macrophages. The dissolved material is excreted via urine, if there is no further metabolization within the body. The pathophysiology of the alveolar clearance mechanisms in the human lung can be studied by a magnetic tracer technique (magnetopneumography). Ferromagnetic magnetite test-particles are deposited in the periphery of the lung by controlled inhalation. After magnetization and particle alignment in a strong external magnetic field pulse, the amount of retained particles can be detected by a sensitive magnetic field sensor (SQUID, superconducting quantum interference device). Long lasting cigarette smoking and chronic lung inflammations (sarcoidosis, interstitial lung fibrosis) induce a significant impairment of alveolar clearance capacity, while patients with chronic bronchitis show only a moderate impairment of alveolar clearance.

Aerosols↗
PubMed1998

Saccular aneurysm induction by elastase digestion of the arterial wall: a new animal model.

OBJECTIVE: To develop a rabbit aneurysm model that is more realistic in gross appearance and histological features than previous models and to enable the development of a larger animal model. METHODS: Ten rabbits received porcine pancreatic elastase, five at the right common carotid artery bifurcation and five others at the right superior thyroid artery origin. One control animal received collagenase and another received papaverine, each at the right superior thyroid artery origin. The agents were topically delivered to the arterial adventitia with a microsyringe after surgical exposure of the targeted arteries. The arteries were monitored for aneurysm growth with a video camera for up to 3 hours and were then removed and processed for histology. RESULTS: Saccular aneurysms developed in one of five animals after elastase application at the carotid bifurcation and in all five animals receiving elastase at the superior thyroid artery origin. Among the six aneurysms, recurrent minor hemorrhages occurred in four, thrombosis of the aneurysm sac in three, and rupture causing severe bleeding in one. Histological sections revealed thin-walled aneurysms composed only of collagen fibers and some cellular elements. No saccular dilation resulted from papaverine application. Collagenase application resulted in a hemorrhagic-thrombotic lesion in the arterial wall but no aneurysm formation. CONCLUSION: Arterial saccular aneurysms were induced in rabbits by topical application of elastase with an easy and efficient method. These aneurysms are histologically similar to natural aneurysms, and their arterial nature renders them more authentic than those of surgical models. This aneurysm model may serve as a foundation for further aneurysm research.

Animals↗
PubMed2005

Theoretically modeling microarray with the chemical equilibrium and thermodynamics.

To date, the idea that microarray may shed the light on cellular processes by identifying groups of genes that appear to be co-expressed seems to remain a dream. This is partly because that there are some blank (meaning the knowledge is unavailable) or even erroneous areas in the fundamental theory in this field. This paper attempts to present the digest of microarray hybridization system with chemical thermodynamics, theoretically clarifying some misunderstandings and looking for answers to some critical questions around this technology, such as the mechanisms and conditions of quantitative measuring by hybridization reaction, the reasons of inconsistency of the data and the analysis results and the solutions, how to analyze the data, etc. A theoretical model for the next generation of microarray is proposed. We believe that this model is universal, laying the foundation for microarray technology from array design through the data analysis.

Computer Simulation↗
PubMed2025

A Systematic Review of Spatial Epidemiological Modeling Approaches Applied During the COVID-19 Pandemic.

BACKGROUND: A wide range of epidemiological modeling approaches have been applied to the SARS-CoV-2 pandemic, which presents an opportunity to assess common approaches applied to specific research questions. Spatial models interrogate how heterogeneities and host movement dynamics influence local and regional patterns of disease, issues that were of great interest for understanding and controlling SARS-CoV-2. OBJECTIVE: Here we present a systematic review of spatial epidemiological modeling approaches of SARS-CoV-2. We describe common themes and highlight unique strategies, providing a foundation for researchers to devise spatial models most appropriate for future pathogens and epidemics. Our review also categorizes the research questions that were addressed with spatial models, highlights parameter estimation techniques, and describes the cyber infrastructure used for model development. METHODS: We conducted a systematic review using Web of Science and a standardized set of keywords, followed by thorough examination of abstracts and full texts to determine which studies met our inclusion criteria. To guide our description and comparisons of models, we developed a Geography, Population, Movement (GPM) framework that conceptualizes the interactions between three distinct subcomponents of any spatial model. The geographic model represents the physical arena in which the model is implemented, the intra-population model describes the transmission and disease processes that occur within distinct spatial units of the geography, and the movement model describes the algorithms that dictate how hosts move among spatial units within the geography. RESULTS: The search identified a total of 193 articles, of which 109 were included in our review. The most abundant intra-population modeling methods were agent-based (47.7%) and compartmental modeling (29.4%) approaches. Movement models ranged in complexity, with the most complex models implementing commuter movement among many points of interest in the geographic arena, which were sometimes parameterized by fine-scale mobility data. Geographic models ranged from describing microcosms, such as single classrooms, all the way up to multi-country models. Of the 63.3% of models studies that specified the programming language used, we detected ten different languages, with Matlab and Python being the most frequent, although only 30.6% of studies provided open-access code for their models. We also described eight specialized software systems that were used to construct agent-based or compartment models of COVID-19. CONCLUSIONS: Our review identified and characterized a variety of spatial modeling strategies and software that were usefully employed to address many relevant epidemiological questions for COVID-19. Future research is needed to quantitatively assess which modeling approaches are most appropriate in specific situations, to answer specific questions, or to apply to certain disease systems. Moreover, future cyberinfrastructure could help to modularize and standardize modeling approaches, which would increase transparency and reproducibility, and which would facilitate a detailed examination of which model attributes relate to model performance in a variety of contexts.

COVID-19↗
PubMed2001

The EFQM Excellence Model. German experiences with the EFQM approach in health care.

OBJECTIVE: To expand on previous reports by illustrating experiences German health services organizitions made in their assessment against the European Foundation for Quality Management (EFQM) Excellence Model. To provide an evaluation of the EFQM method compared to peer auditing and accreditation concepts within health care. DESIGN: To indicate the EFQM method and scoring system and draft the process of self-assessment in health services organizitions. To refer to the experiences of German health care pioneers during their early assessments. RESULTS: Using the EFQM approach, an organizition can earn up to 1.000 points. More than 50% of German hospitals scored 200-300 points and not a single organizition achieved over 450 points. To make a comparison, the best score obtained in an industrial setting was between 650-750 points. In addition to the numbers, this report describes success factors and best practices of self-assessments, as well as limitations, barriers and lessons learned during the implementation phase. CONCLUSION: The Excellence Model is a systematic quality management approach to gain competitive advantage. It is non-governmental, non-financier driven, and generic enough to address health care issues. Having its foundation in industry, however, it is not specific enough to cover all areas relevant to health care. Integrating the management-smart method of self-assessment with clinical standards as delivered by peer auditing and accreditation systems generates the potential to deliver excellence in health care.

Benchmarking↗
PubMed2004

Conversion rates in laparoscopic colorectal surgery: a predictive model with, 1253 patients.

BACKGROUND: This study aimed all develop a mathematical model for predicting the conversion rate for patients undergoing laparoscopic colorectal surgery. METHOD: This descriptive single-center study used routinely collected clinical data from 1,253 patients undergoing laparoscopic surgery between November 1991 and April 2003. A two-level hierarchical regression model was used to identify patient, surgeon, and procedure-related factors associated with conversion of laparoscopic to open surgery. The model was internally validated and tested using measures of discrimination and calibration. Exclusion criteria for laparoscopic colectomy included a body mass greater than 50, lesion diameter exceeding 15 cm, and multiple prior major laparotomies (exclusive of appendectomy, hysterectomy, and cholecystectomy). RESULTS: The average conversion rate for the study population was 10.0% (95% confidence interval [CI], 8.3-11.7%). The independent predictors of conversion of laparoscopic to open surgery were the body mass index (odds ratio [OR], 2.1 per 10 Americans Society of Anesthesiology units increase), (ASA) grade 3 or 4, 1 or 2 (OR, 3.2, 5.8), type of resection (low rectal, left colorectal, right colonic vs small/other bowel procedures; OR, 8.82, 4.76, 2.98), presence of intraoperative abscess (OR, 3.60) or fistula (OR, 4.73), and surgeon seniority (junior vs senior staff OR, 1.56). The model offered adequate discrimination (area under receiver operator characteristic curve, 0.74) and excellent agreement (p = 0.384) between observed and model-predicted conversion rates (range of calibration, 3-32% conversion rate). CONCLUSIONS: Laparoscopic conversion rates are dependent on a multitude of factors that require appropriate adjustment for case mix before comparisons are made between or within centers. The Cleveland Clinic Foundation (CCF) laparoscopic conversion rate model is a simple additive score that can be used in everyday practice to evaluate outcomes for laparoscopic colorectal surgery.

Adolescent↗
PubMed1994

POHEM--a framework for understanding and modelling the health of human populations.

A variety of developments have come together to serve as both an impetus to and foundation for the development of a new POpulation HEalth Model (POHEM) at Statistics Canada. Part of the impetus is statistical and derives from weaknesses in Canada's health statistics programme--particularly the lack of balance between information on health outcomes and health care resource consumption, and the absence of a coherent statistical structure. The other major impetus is the need for rational processes for managing and allocating resources to improve the health of Canadians. The foundation for the development of this model has come from the revolution in computing. Dramatic improvements have opened up new methodological opportunities, particularly sophisticated simulation modelling and detailed analyses of large volumes of microdata. POHEM is designed to build on these increasingly powerful methods in order to meet health statistical and policy needs. At this time, POHEM is like a partially-completed building. This article reviews its motivation, the overall architectural plan, and the portion of the structure already completed. A major portion of POHEM is devoted to the explicit modelling of chronic disease processes, using monte carlo microsimulation methods. The article concludes with illustrations of a few recent applications, focusing on the joint patterns of smoking, cholesterol and heart disease, osteoarthritis and lung cancer morbidity. While POHEM has been developed in a Canadian context, work is under way to create a version that can be used in other countries.

Adolescent↗
PubMed2000

Cellular energetics analysis by a mathematical model of energy balance: estimation of parameters in human skeletal muscle.

Cellular energy balance requires that the physiological demands by ATP-utilizing functions be matched by ATP synthesis to sustain muscle activity. We devised a new method of analysis of these processes in data from single individuals. Our approach is based on the logic of current information on the major mechanisms involved in this energy balance and can quantify not directly measurable parameters that govern those mechanisms. We use a mathematical model that simulates by ordinary, nonlinear differential equations three components of cellular bioenergetics (cellular ATP flux, mitochondrial oxidative phosphorylation, and creatine kinase kinetics). We incorporate data under resting conditions, during the transition toward a steady state of stimulation and during the transition during recovery back to the original resting state. Making use of prior information about the kinetic parameters, we fitted the model to previously published dynamic phosphocreatine (PCr) and inorganic phosphate (P(i)) data obtained in normal subjects with an activity-recovery protocol using (31)P nuclear magnetic resonance spectroscopy. The experiment consisted of a baseline phase, an ischemic phase (during which muscle stimulation and PCr utilization occurred), and an aerobic recovery phase. The model described satisfactorily the kinetics of the changes in PCr and P(i) and allowed estimation of the maximal velocity of oxidative phosphorylation and of the net ATP flux in individuals both at rest and during stimulation. This work lays the foundation for a quantitative, model-based approach to the study of in vivo muscle energy balance in intact muscle systems, including human muscle.

Energy Metabolism↗
PubMed2003

Bioterrorism meets privacy: an analysis of the Model State Emergency Health Powers Act and the HIPAA privacy rule.

Ms. Bruce's paper analyzes the interplay between the Model State Emergency Health Powers Act and the HIPAA Privacy Rule. The article begins by examining specific relevant provisions of the Act and Rule. Next, it traces the history of public health law through the court system and then uses this foundation to discuss how the Model State Emergency Health Powers Act and the HIPAA Privacy Rule could co-exist, protecting Americans in the case of a bioterror attack, while being appropriately sensitive to the confidentiality of private health information.

Bioterrorism↗
PubMed1995

On the foundation and structure of medical informatics.

The authors from China and the United States take medical informatics from theory to practice by improving its research, application, and dissemination and by expanding its educational potential. We built a theoretical model and discussed its definition, approach, foundation, principles, and structure. Medical informatics is the interdisciplinary study of information science applied to medicine and health care. Its developing approach is transplantation. The foundation of medical informatics has "building blocks" of knowledge. They are: information procedure models; information classification principles; information processing methodologies; and functional hierarchical principles of information systems. The structure of medical informatics includes the main knowledge branches and their logical relations. There are four big branches: computer tools and systems methods; engineering equipment and methods; medical fields information systems; and health care management systems. Based on the investigation of the professional status (its theory and application, and its forms and the contents) of medical informatics, it can be seen that this new discipline is becoming mature.

China↗
PubMed2006

Exact coalescent for the Wright-Fisher model.

The Kingman coalescent, which has become the foundation for a wide range of theoretical as well as empirical studies, was derived as an approximation of the Wright-Fisher (WF) model. The approximation heavily relies on the assumption that population size is large and sample size is much smaller than the population size. Whether the sample size is too large compared to the population size is rarely questioned in practice when applying statistical methods based on the Kingman coalescent. Since WF model is the most widely used population genetics model for reproduction, it is desirable to develop a coalescent framework for the WF model, which can be used whenever there are concerns about the accuracy of the Kingman coalescent as an approximation. This paper described the exact coalescent theory for the WF model and develops a simulation algorithm, which is then used, together with an analytical approach, to study the properties of the exact coalescent as well as its differences to the Kingman coalescent. We show that the Kingman coalescent differs from the exact coalescent by: (1) shorter waiting time between successive coalescent events; (2) different probability of observing a topological relationship among sequences in a sample; and (3) slightly smaller tree length in the genealogy of a large sample. On the other hand, there is little difference in the age of the most recent common ancestor (MRCA) of the sample. The exact coalescent makes up the longer waiting time between successive coalescent events by having multiple coalescence at the same time. The most significant difference among various summary statistics of a coalescent examined is the sum of lengths of external branches, which can be more than 10% larger for exact coalescent than that for the Kingman coalescent. As a whole, the Kingman coalescent is a remarkably accurate approximation to the exact coalescent for sample and population sizes falling considerably outside the region that was originally anticipated.

Algorithms↗
PubMed2000

The EFQM excellence model: European and Dutch experiences with the EFQM approach in health care. European Foundation for Quality Management.

One way to meet the challenges in creating a high performance organization in health care is the approach of the European Foundation for Quality Management (EFQM). The Foundation is in the tradition of the American Malcolm Baldrige Award and was initiated by the European Commission and 14 European multi-national organizations in 1988. The essence of the approach is the EFQM Model, which can be used as a self-assessment instrument on all levels of a health care organization and as an auditing instrument for the Quality Award. In 1999 the EFQM Model was revised but its principles remained the same. In The Netherlands many health care organizations apply the EFQM Model. In addition to improvement projects, peer review of professional practices, accreditation and certification, the EFQM Approach is used mainly as a framework for quality management and as a conceptualization for organizational excellence. The Dutch National Institute for Quality, the Instituut Nederlandse Kwaliteit, delivers training and supports self-assessment and runs the Dutch quality award programme. Two specific guidelines for health care organizations, 'Positioning and Improving' and 'Self-Assessment', have been developed and are used frequently. To illustrate the EFQM approach in The Netherlands, the improvement project of the Jellinek Centre is described. The Jellinek Centre conducted internal and external assessments and received in 1996, as the first health care organization, the Dutch Quality Prize.

Academies and Institutes↗
PubMed2003

Pathogenesis of Goodpasture syndrome: a molecular perspective.

Goodpasture (GP) syndrome is a form of anti-glomerular basement membrane (GBM) disease, in which autoantibodies bind to alpha3(IV) collagen in GBM causing rapidly progressive glomerulonephritis and pulmonary hemorrhage. The conformational GP epitopes have been mapped to 2 regions within the noncollagenous (NC1) domain of the alpha3(IV) chain. Recently, we described the molecular organization of the autoantigen in the native alpha3alpha4alpha5(IV) collagen network of the GBM. The crystal structure of the NC1 domain has revealed how the GP epitopes are sequestered in the native GBM. Further insight into the pathogenesis of disease has been obtained from better animal models. These advances provide a foundation for the development of new specific therapies.

Animals↗
PubMed2004

Educating the next generation of pediatricians in urban health care: the Anne E. Dyson Community Pediatrics Training Initiative.

To improve the health of children who are exposed to urban health risks, there has been a national recognition of the need for better models of training pediatricians. In 2000, in response to this need, the Dyson Foundation launched a new residents-training model that focuses on community health and advocacy, The Anne E. Dyson Community Pediatrics Training Initiative (the Initiative). The Initiative is made up of 12 programs at ten sites, which are working in their communities to improve the health of the children. At its core are five objectives: to equip residents with tools and knowledge to provide community-based health care, to make use of community resources so that residents learn to practice as medical home providers, to engage residents in the communities in which they work, to develop meaningful partnerships between departments of pediatrics and their communities, and to enhance pediatrics training through interdisciplinary collaborations among schools and departments. Curricular approaches at the participating sites differ slightly, but all have explicitly incorporated teaching community pediatrics into their standard rotations and continuity clinics. The authors showcase the programs of the Initiative and explore how the programs have sought buy-in from their parent institutions, faculty, residents, and communities.

Academic Medical Centers↗
PubMed2006

Three-dimensional mechanical properties of porcine coronary arteries: a validated two-layer model.

The normal coronary artery consists of two mechanically distinct layers: intima-media and adventitia. The objective of this study is to establish a two-layer three-dimensional (3-D) stress-strain relation of porcine coronary arteries. Experimental measurements were made by a series of biaxial tests (inflation and axial extension) of intact coronary arteries and, subsequently, their corresponding intima-media or adventitia layer. The Fung-type exponential strain energy function was used to describe the 3-D strain-stress relation for each layer and the intact wall. A genetic algorithm was used to determine the material constants in the Fung-type constitutive equation by curve fitting the experimental data. Because one layer must be sacrificed before the other layer can be tested, the material property of the missing layer was computed from the material constants of the intact vessel and the tested layer. A total of 20 porcine hearts were used: one group of 10 hearts for the left anterior descending artery and another group of 10 hearts for the right coronary artery. Each group was further divided into two subgroups of five specimens tested for the intact wall and the intima-media layer and for the intact wall and the adventitia layer. Our results show statistically significant differences in the material properties of the two layers. The mathematical model was validated by experimental stress-strain data for individual layers. The validated 3-D constitutive model will serve as a foundation for formulation of layer-specific boundary value problems in coronary physiology and cardiology.

Algorithms↗