RESUMEN
The Mississippi State Department of Health tuberculosis program serves a rural southeastern US state of 2.9 million people in an area of 121,489 km(2) (46,907 square miles). Statewide, directly observed therapy (DOT) began in 1986. To evaluate the program's effectiveness, trends in Centers for Disease Prevention and Control program indicators for 1981-2005 were compared and found to be significant (P < 0.0001). Inclusion of rifampin and pyrazinamide in the regimens was reviewed. An annual decline in cases and case rates began in 1990, falling by 65% by 2005. Successful DOT is feasible over a large geographic area.
Asunto(s)
Antituberculosos/uso terapéutico , Terapia por Observación Directa/estadística & datos numéricos , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Adolescente , Adulto , Anciano , Antibióticos Antituberculosos/uso terapéutico , Centers for Disease Control and Prevention, U.S. , Niño , Preescolar , Bases de Datos Factuales , Femenino , Política de Salud , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , Pirazinamida/uso terapéutico , Rifampin/uso terapéutico , Población Rural , Estados Unidos , Adulto JovenRESUMEN
Pharaoh's ants organise their foraging system using three types of trail pheromone. All previous foraging models based on specific ant foraging systems have assumed that only a single attractive pheromone is used. Here we present an agent-based model based on trail choice at a trail bifurcation within the foraging trail network of a Pharaoh's ant colony which includes both attractive (positive) and repellent (negative) trail pheromones. Experiments have previously shown that Pharaoh's ants use both types of pheromone. We investigate how the repellent pheromone affects trail choice and foraging success in our simulated foraging system. We find that both the repellent and attractive pheromones have a role in trail choice, and that the repellent pheromone prevents random fluctuations which could otherwise lead to a positive feedback loop causing the colony to concentrate its foraging on the unrewarding trail. An emergent feature of the model is a high level of variability in the level of repellent pheromone on the unrewarding branch. This is caused by the repellent pheromone exerting negative feedback on its own deposition. We also investigate the dynamic situation where the location of the food is changed after foraging trails are established. We find that the repellent pheromone has a key role in enabling the colony to refocus the foraging effort to the new location. Our results show that having a repellent pheromone is adaptive, as it increases the robustness and flexibility of the colony's overall foraging response.
Asunto(s)
Comunicación Animal , Hormigas/fisiología , Simulación por Computador , Conducta Alimentaria/fisiología , Feromonas/fisiología , Animales , Conducta de Elección , Modelos BiológicosRESUMEN
Polycystic liver disease (PLD) is usually associated with polycystic kidney disease but may also occur as an isolated finding in a rarer genetically distinct disease. In either case, the cyst burden will progress over time and, in rare cases, may affect liver function or become symptomatic due to massive hepatomegaly. The character, distribution, location, and size of hepatic cysts are important. Computed tomography, magnetic resonance imaging, or ultrasonography may provide the surgeon with valuable preoperative information, such as the location of infected or hemorrhagic cysts that may be responsible for symptoms. Less invasive cyst aspiration or fenestration may provide temporary relief from dominant or symptomatic cysts, but these cysts will recur in up to 75% of patients. Cyst fenestration with partial hepatic resection and liver transplantation are two therapies that provide more permanent resolution of symptoms in patients with extensive hepatic involvement. However, the higher risk of complications associated with more aggressive surgical therapy must be considered when determining the appropriate therapy for a given patient. Knowledge of the cyst patterns and available treatment options in patients with PLD will help the radiologist provide the referring clinician with important information for therapeutic decision making.
Asunto(s)
Quistes/diagnóstico , Diagnóstico por Imagen/métodos , Hepatopatías/diagnóstico , Trasplante de Hígado , Toma de Decisiones , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Cuidados Preoperatorios/métodos , Pronóstico , Medición de Riesgo/métodosRESUMEN
Fitness functions derived from certain types of white-box test goals can be inadequate for evolutionary software test data generation (Evolutionary Testing), due to a lack of search guidance to the required test data. Often this is because the fitness function does not take into account data dependencies within the program under test, and the fact that certain program statements may need to have been executed prior to the target structure in order for it to be feasible. This paper proposes a solution to this problem by hybridizing Evolutionary Testing with an extended Chaining Approach. The Chaining Approach is a method which identifies statements on which the target structure is data dependent, and incrementally develops chains of dependencies in an event sequence. By incorporating this facility into Evolutionary Testing, and by performing a test data search for each generated event sequence, the search can be directed into potentially promising, unexplored areas of the test object's input domain. Results presented in the paper show that test data can be found for a number of test goals with this hybrid approach that could not be found by using the original Evolutionary Testing approach alone. One such test goal is drawn from code found in the publicly available libpng library.
Asunto(s)
Simulación por Computador , Evolución Molecular , Algoritmos , Gráficos por Computador , Reproducibilidad de los Resultados , Programas Informáticos , Estadística como AsuntoRESUMEN
We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models.
Asunto(s)
Algoritmos , Inteligencia Artificial , Calcio/metabolismo , Comunicación Celular/fisiología , Células Epiteliales/citología , Células Epiteliales/fisiología , Modelos Biológicos , Animales , Movimiento Celular/fisiología , Proliferación Celular , Células Cultivadas , Simulación por Computador , Humanos , Conducta SocialRESUMEN
The investigation of contacts of tuberculosis (TB) cases is an essential part of Mississippi's comprehensive TB program. A case interview is initiated within 24 hours, and the concentric circle method is used to identify and evaluate contacts. High-risk contacts of pulmonary cases are located and evaluated within 10 days. A follow-up evaluation is conducted by a TB consultant to determine the need for additional tests. All pulmonary contacts receive a 12-week follow-up tuberculin skin test (TST) if the initial test is negative. Directly observed treatment for latent TB infection (LTBI) is offered to all children aged <15 years, human immunodeficiency virus positive persons and others deemed at high risk for developing active disease. Mississippi contact investigations in 1990-1998 identified 212 (0.7%) cases of TB, and 5608 (17.5%) contacts with LTBI. In that period, the proportion of cases with contacts identified averaged 99%, with a mean number of contacts per case of 15.4. At the same time, 95% of contacts completed an evaluation for active TB and LTBI. Among contacts <15 years of age, >96% have completed LTBI treatment annually since 1992. Cases and case rates in Mississippi have decreased annually during this period. Effective TB contact investigation yields immediate results by identifying other sources of TB transmission and preventing future transmission through appropriate treatment of contacts with LTBI.
Asunto(s)
Trazado de Contacto/métodos , Población Rural , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Humanos , Mississippi/epidemiología , Evaluación de Procesos y Resultados en Atención de SaludRESUMEN
The aim of this paper is to prove the suitability of a parallel distributed computational model, communicating X-machines, to simulate in a natural way a well established model of molecular computation, P systems, and to present some further benefits of the approach allowing us to check for some formal properties. A set of rules to transform any P system with symbol-objects into a communicating X-machine model is presented and a variation of temporal logic for X-machines is briefly discussed, which facilitates model checking of desired properties of the system. Finally, the benefits resulting from the transformation are discussed.
Asunto(s)
Algoritmos , Comunicación Celular/fisiología , Membrana Celular/fisiología , Simulación por Computador , Computadores Moleculares , Espacio Extracelular/fisiología , Almacenamiento y Recuperación de la Información/métodos , Modelos Biológicos , Metodologías Computacionales , Ambiente , Transporte Iónico/fisiología , Dinámicas no Lineales , Terminología como AsuntoRESUMEN
In this paper the behaviour of a bee colony is modelled as society of communicating agents acting in parallel and synchronising their behaviour. Two computational approaches for defining the agents behaviour are introduced and compared. Their common features as well as the complementary aspects making them suitable for merging together into a more complex model.
Asunto(s)
Conducta Animal , Modelos Biológicos , Animales , Abejas/fisiología , Comunicación , Simulación por Computador , Conducta SocialRESUMEN
Computational models have been of interest in biology for many years and have represented a particular approach to trying to understand biological processes and phenomena from a systems point of view. Much of the early work was rather abstract and high level and probably seemed to many to be of more philosophical than practical value. There have, however, been some advances in the development of more realistic models and the current state of computer science research provides us with new opportunities through both the emergence of models that can model seriously complex systems and also the support that modern software can give to the modelling process. This paper describes a few of the early simple models and then goes on to look at some new ideas in the area with a particular application drawn from the world of mycology. Some general principles relating to how new and emerging computational techniques can help to represent and understand extremely complex models conclude the paper.
Asunto(s)
Simulación por Computador , Magnaporthe/fisiología , Modelos Biológicos , Enfermedades de las Plantas , Biología Computacional , Micología , Oryza/microbiologíaRESUMEN
This paper proposes a specification language, hybrid projection temporal logic of modelling, analyzing and verifying biological systems which can be considered, in general, to be hybrid systems consisting of a non-trivial mixture of discrete and continuous components. The syntax and semantics of the logic are presented, and some examples of hybrid systems are modelled to illustrate the formalism.
Asunto(s)
Lógica , Modelos Biológicos , Reacciones Antígeno-Anticuerpo , Reproducibilidad de los Resultados , TiempoRESUMEN
A prospective study was carried out to determine the factors which influence response to antithyroid drug treatment in Graves' disease and to assess their predictive value. Eleven variables were included in the assessment and were subjected to discriminant analysis, log rank test and "survival" analysis. The patients were observed for a considerable period (mean duration 51 months). Carbimazole (mean total dose 8 g) was given in combination with thyroxine for an average of eight months to 72 patients. Thirty-five patients relapsed and 37 remain in remission. Thyrotrophin binding inhibiting immunoglobulins (TBII) were detectable in 74 per cent of patients at diagnosis and thyroid stimulating antibodies detectable in 70 per cent. At the end of treatment thyrotrophin binding inhibiting immunoglobulins and thyroid stimulating antibodies were present in 36 and 27 per cent of patients respectively. Levels of thyrotrophin binding inhibiting immunoglobulins were significantly higher both before and after treatment in the group who relapsed, but were not of prognostic significance in an individual patient unless the value was extremely high (TBII index greater than 70). The presence of thyroid stimulating antibodies was of no value in predicting outcome. HLA typing confirmed the known association of Graves' disease with HLA B8 and HLA DR3 but neither of these antigens conferred and increased likelihood of relapse. The likelihood of relapse is shown to be directly related to the severity of the disease at the time of diagnosis, as measured by the serum total T3, and to the size of the thyroid gland; it is not affected by age, family history of thyroid disease or ophthalmopathy. The data indicate that antithyroid drug treatment can be expected to induce long-term remission in patients with mild disease (T3 less than 5 nmol/l) and small thyroids; carbimazole at this dose level is inappropriate for patients with severe disease (T3 greater than 9 nmol/) and large goitres.
Asunto(s)
Carbimazol/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Tiroxina/uso terapéutico , Adolescente , Adulto , Anticuerpos/análisis , Quimioterapia Combinada , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/genética , Enfermedad de Graves/inmunología , Antígenos HLA/análisis , Humanos , Inmunoglobulina G/análisis , Inmunoglobulinas Estimulantes de la Tiroides , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Triyodotironina/sangreRESUMEN
Antibodies that inhibit the stimulation of the thyroid by TSH have been studied in 63 patients with primary hypothyroidism of whom 34 had thyroid atrophy and 29 goitrous Hashimoto's thyroiditis. The method used measured the secretion of tri-iodothyronine (T3) from porcine thyroid slices incubated in vitro. The aims of the study were to assess the frequency and clinical correlates of blocking antibodies in an unselected series of patients, to establish their IgG nature and to examine their action in relation to the TSH receptor. Blocking antibodies were found in 25% of patients and occurred in association with both atrophic (32%) and goitrous (17%) hypothyroidism. These antibodies did not bind TSH (with one exception) nor did they inhibit binding of TSH to its receptor (also with one exception). Blocking-antibody activity was abolished by treatment of the serum with anti-hIgG or with protein A, and the activity was purified from serum by affinity chromatography on protein A sepharose-4B, thus establishing the IgG nature of the antibodies. The stimulation of T3 secretion by thyroid-stimulating antibodies was also blocked and in one case, where IgG did not block stimulation by bTSH, stimulation by hTSH was blocked. Antibodies blocking the action of TSH probably represent an important mechanism in the pathogenesis of primary hypothyroidism in some patients.
Asunto(s)
Anticuerpos/inmunología , Autoanticuerpos/inmunología , Hipotiroidismo/inmunología , Tirotropina/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Atrofia , Autoanticuerpos/metabolismo , Bioensayo , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulinas Estimulantes de la Tiroides , Masculino , Persona de Mediana Edad , Receptores de Tirotropina/metabolismo , Glándula Tiroides/inmunología , Glándula Tiroides/patología , Tiroiditis Autoinmune/inmunología , Tirotropina/metabolismoRESUMEN
The effect of subtotal thyroidectomy on thyroid stimulating antibodies (TSAb), thyrotrophin binding inhibitory immunoglobulins (TBII) and antimicrosomal antibodies (MsAb) was studied in 26 patients with Graves' hyperthyroidism treated pre-operatively with propranolol, but without antithyroid drugs. Following surgery, two patients relapsed in the first year and eight patients became hypothyroid. Eighteen patients (69%) had detectable TSAb at entry and no significant change in titre was seen during propranolol therapy. Following surgery TSAb levels fell within 24 h in eight patients, and at 6 weeks only seven patients had detectable TSAb. TSAb were still detectable in seven patients at 6 months. TSAb activity did not predict the late relapses. TBII were present in 13 patients (50%) before surgery and titres remained unchanged in all but two patients during the immediate postoperative period. At 6 weeks TBII had disappeared from the serum of only three patients. During the early post-operative period TBII became transiently detectable in five of the 13 patients initially TBII negative. The two patients who subsequently relapsed remained TBII positive throughout. Microsomal antibodies were present in the sera of 22 patients (85%). Surgery was followed by a decline in titre, which was substantial in only six of 13 patients studied in detail. Thus, in 92% patients hyperthyroidism was successfully eradicated. Propranolol treatment had no effect on antibody activity. TSAb and TBII disappeared from the circulation in 61% and 46% patients, respectively. These data are compatible with the concept that lymphocytes within the thyroid are the major site of TSAb production but other important sites for synthesis of thyroidal autoantibodies probably exist. Although outcome from surgery could not be accurately predicted from TSAb or TBII status either pre- or post-operatively, the two patients who relapsed had the most severe disturbances of thyroid autoimmunity; all patients in whom initially detectable TSAb or TBII disappeared remained in remission.
Asunto(s)
Enfermedad de Graves/cirugía , Propranolol/uso terapéutico , Adolescente , Adulto , Anticuerpos/análisis , Femenino , Enfermedad de Graves/inmunología , Humanos , Inmunoglobulinas/análisis , Masculino , Microsomas/inmunología , Persona de Mediana Edad , Cuidados Preoperatorios , Glándula Tiroides/inmunología , TiroidectomíaRESUMEN
The development and evaluation of a TSH radioligand receptor assay for TSH-binding-inhibiting immunoglobulins and its application to the study of patients with Graves' disease are described. Optimal conditions for the binding of 125I-TSH to solubilised thyroid membranes are defined. Polyethylene glycol precipitation was employed to prepare immunoglobulins from serum for assay and gave results comparable to ammonium sulphate precipitation. Immunoglobulins from normal serum did not interfere in the assay; preparations from patients with untreated Graves' disease gave positive results in 44 out of 56 cases. Coefficients of intra- and inter-assay variation were 7.0% and 9.8% respectively. The method is therefore not only sensitive and reproducible but is sufficiently simple and rapid for routine application.
Asunto(s)
Enfermedad de Graves/inmunología , Inmunoglobulina G/análisis , Sulfato de Amonio , Membrana Celular/metabolismo , Precipitación Química , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulinas Estimulantes de la Tiroides , Polietilenglicoles , Ensayo de Unión Radioligante , Glándula Tiroides/metabolismo , Tirotropina/inmunología , Tirotropina/metabolismoRESUMEN
An IgG which binds specifically to retro-orbital antigen has been detected in patients with Graves' ophthalmopathy. By means of an assay which detects ophthalmopathic immunoglobulin (OIg) in patients' serum with an antigen prepared from porcine retro-orbital muscle, levels of OIg above the normal reference range were found in 21 of 33 (64%) patients with active untreated ophthalmopathy, in 3 of 12 (25%) with active disease already receiving steroid treatment, and in 3 of 18 (16%) with longstanding inactive eye disease. OIg was found in only 1 of 22 thyroid patients without eye disease. There was no correlation of OIg with thyrotropin-binding-inhibiting immunoglobulin nor with thyroid microsomal antibody, and there was no clear association with thyroglobulin antibody. Ophthalmopathy seems to be distinct from Graves' hyperthyroidism and the autoimmune response is directed to retro-orbital antigens.
Asunto(s)
Oftalmopatías/inmunología , Enfermedad de Graves/inmunología , Inmunoglobulina G/análisis , Animales , Reacciones Antígeno-Anticuerpo , Sitios de Unión de Anticuerpos , Ensayo de Inmunoadsorción Enzimática , Oftalmopatías/etiología , Enfermedad de Graves/complicaciones , Cobayas , Glándula de Harder/inmunología , Humanos , Inmunoglobulinas Estimulantes de la Tiroides , Músculos Oculomotores/inmunología , Porcinos , Glándula Tiroides/inmunologíaRESUMEN
An IgG (ophthalmopathic immunoglobulin) that binds to retro-orbital antigen was identified in serum from patients with active Graves' ophthalmopathy, and its nature and specificity were investigated. Dose related binding of this immunoglobulin to retro-orbital antigens prepared from guinea pig harderian gland or porcine eye muscle was found, which could be abolished by prior incubation with antigen. The immunoglobulin did not bind to thyroid membranes, thyroid microsomes, or thyroglobulin or interact with liver, skeletal muscle, or fat membranes. Serum with high activity of thyrotrophin binding inhibiting immunoglobulin did not react with retro-orbital antigen, and this activity was not affected by preincubation of the serum with retro-orbital antigen. Thyroid stimulating hormone was also without effect on retro-orbital antigen. It is concluded that Graves' ophthalmopathy is associated with a specific ophthalmopathic immunoglobulin that reacts with retro-orbital antigen as distinct from thyroid antigens, and that the autoimmune response is directed towards retro-orbital antigens. This suggests that the ophthalmopathy is an entity distinct from autoimmune thyroid disease.