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PubMed1980

Molecular mechanism of acetylcholine receptor-controlled ion translocation across cell membranes.

Two molecular processes, the binding of acetylcholine to the membrane-bound acetylcholine receptor protein and the receptor-controlled flux rates of specific inorganic ions, are essential in determining the electrical membrane potential of nerve and muscle cells. The measurements reported establish the relationship between the two processes: the acetylcholine receptor-controlled transmembrane ion flux of (86)Rb(+) and the concentration of carbamoylcholine, a stable analog of acetylcholine. A 200-fold concentration range of carbamoylcholine was used. The flux was measured in the millisecond-to-minute time region by using a quench flow technique with membrane vesicles prepared from the electric organ of Electrophorus electricus in eel Ringer's solution at pH 7.0 and 1 degrees C. The technique makes possible the study of the transmembrane transport of specific ions, with variable known internal and external ion concentrations, in a system in which a determinable number of receptors is exposed to a known concentration of ligand. The response curve of ion flux to ligand was sigmoidal with an average maximum rate of 84 sec(-1). Carbamoylcholine induced inactivation of the receptor with a maximum rate of 2.7 sec(-1) and a different ligand dependence so that it was fast relative to ion flux at low ligand concentration but slow relative to ion flux at high ligand concentration. The simplest model that fits the data consists of receptor in the active and inactive states in ligand-controlled equilibria. Receptor inactivation occurs with one or two ligand molecules bound. For channel opening, two ligand molecules bound to the active state are required, and cooperativity results from the channel opening process itself. With carbamoylcholine, apparently, the equilibrium position for the channel opening step is only one-fourth open. The integrated rate equation, based on the model, predicts the time dependence of receptor-controlled ion flux over the concentration range of carbamoylcholine investigated. The values of the constants in the rate equation form the basis for predicting receptor-controlled changes in the transmembrane potential of cells and the conditions leading to transmission of signals between cells.

Animals↗

PubMed1999

A prediction model for moderate or severe dehydration in children with diarrhoea.

A hospital-based unmatched case-control study (387 cases and 387 controls) was carried out at the Government Medical College Hospital, Nagpur, India, to devise and validate a risk-scoring system for predicting the development of moderate or severe dehydration in children, aged less than five years, with acute watery diarrhoea. On unconditional multiple logistic regression, 12 risk factors--infancy, minority religion, undernutrition, not washing hands by mother before preparation of food, frequency of stools > 8/day, frequency of vomiting > 2/day, measles in previous 6 months, withdrawal of breast-feeding/other feedings, withdrawal of fluids during diarrhoea, not giving oral rehydration solutions (ORS), home available fluids and both during diarrhoea--were significant. Based on regression coefficients, these factors were ascribed statistical weights of 5, 5, 4, 4, 22, 9, 11, 13, 5, 5, 5, and 7 respectively. The receiver-operating characteristic curve suggested a total score of 48 to be the best cut-off for predicting the development of moderate or severe dehydration. At this cut-off, the sensitivity, specificity, positive predictive value, Cohen's kappa, and overall predictive accuracy were 0.81, 0.81, 0.81, 0.61, and 0.86 respectively. If substantiated by further validation, this system can be used for predicting the development of dehydration at the earlier stage, thereby reducing the mortality associated with life-threatening dehydration.

Acute Disease↗

PubMed2006

Binocular contrast vision at and above threshold.

A fundamental problem for any visual system with binocular overlap is the combination of information from the two eyes. Electrophysiology shows that binocular integration of luminance contrast occurs early in visual cortex, but a specific systems architecture has not been established for human vision. Here, we address this by performing binocular summation and monocular, binocular, and dichoptic masking experiments for horizontal 1 cycle per degree test and masking gratings. These data reject three previously published proposals, each of which predict too little binocular summation and insufficient dichoptic facilitation. However, a simple development of one of the rejected models (the twin summation model) and a completely new model (the two-stage model) provide very good fits to the data. Two features common to both models are gently accelerating (almost linear) contrast transduction prior to binocular summation and suppressive ocular interactions that contribute to contrast gain control. With all model parameters fixed, both models correctly predict (1) systematic variation in psychometric slopes, (2) dichoptic contrast matching, and (3) high levels of binocular summation for various levels of binocular pedestal contrast. A review of evidence from elsewhere leads us to favor the two-stage model.

Contrast Sensitivity↗

PubMed2005

A case-control study of risk factors in men with chronic pelvic pain syndrome.

OBJECTIVE: To compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome. PATIENTS AND METHODS: Self-administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age-matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods. RESULTS: Compared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001). CONCLUSION: A wide range of self-reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS.

Adult↗

PubMed1995

The ion parametric resonance model predicts magnetic field parameters that affect nerve cells.

An ion parametric resonance (IPR) model recently developed by Blanchard and Blackman predicts distinct magnetic field interactions with biological systems based on a selective relation among four factors: the flux density of the static magnetic field, the frequency and flux density (Bac) of the parallel ac magnetic field, and the charge-to-mass ratio of ions of biological relevance. To test this model, PC-12 cells stimulated by nerve growth factor to produce neurites were exposed for 23 h in a 5% CO2 incubator using a multiple-coil exposure system to produce 45 Hz ac and dc (366 mG parallel to ac; less than 2 mG perpendicular to ac) magnetic fields. Our earlier work showed a cycle of inhibition/no inhibition of neurite outgrowth consistent with the IPR model predictions for Bac exposures between 0 and 468 mG rms. The work described here tests neurite outgrowth over a broader range of Bac (233-1416 mG rms). The experimental results remain consistent with earlier results, and with IPR model predictions of a second cycle of inhibition, return to control values, followed by a third cycle of inhibition of neurite outgrowth. These responses support the fundamental relationships predicted by the IPR model. The results have broad significance for biology.

Animals↗

PubMed1990

Restricted diffusion of molecules in porous affinity chromatography adsorbents.

A restricted diffusion model is constructed and solved in order to study the permeability of large adsorbate molecules in the pores of affinity chromatography media, when the adsorbate molecules are adsorbed onto immobilized ligands. The combined effects of steric hindrance at the entrance to the pores and frictional resistance within the pores, as well as the effects of pore size distribution, pore connectivity of the adsorbent, molecular size of adsorbate and ligand, and the fractional saturation of adsorption sites (ligands), are considered. Affinity adsorbents with dilute and high ligand concentrations are examined, and the permeability of the adsorbate in porous networks of connectivity nT is studied by means of effective medium approximation (EMA) numerical solutions. As expected, the permeability of the adsorbate decreases as the size of the adsorbate and/or ligand molecule increases. The permeability also decreases when the fractional saturation of the ligands increases, as well as when the pore connectivity of the network decreases. The dependence of the permeability on the pore connectivity tends to be less marked in adsorbents with concentrated ligand than in porous media with dilute ligand concentration. The conditions are also presented for which the percolation threshold is attained in a number of different systems. The restricted diffusion model and results of this work may be of importance in studies involving the modeling, prediction of the dynamic behavior, design, and control of affinity chromatography (biospecific adsorption) systems employing porous adsorbents. The theoretical results may also have important implications in the selection of a ligand as well as in the selection and construction of an affinity porous matrix, so that the adsorbate of interest can be efficiently separated from a given solution. Furthermore, with appropriate modifications this restricted diffusion model may be used in studies involving the immobilization of ligands or enzymes in porous solids.

Adsorption↗

PubMed2025

Predicting the First Onset of Suicidal Thoughts and Behaviors in Adolescents Using Multimodal Risk Factors: A 4-Year Longitudinal Study.

OBJECTIVE: Suicide is one of the leading causes of death among youth worldwide, yet existing studies that aimed to predict the first onset of suicidal thoughts and behaviors (STB) included a limited number of data modalities and/or focused on adult populations. This study aimed to prospectively predict first-onset STB across 4-year follow-ups in adolescents using an existing STB history classification model that was previously applied to baseline data and a new machine learning model with 195 biopsychosocial features. METHOD: Participants were 7,503 unrelated adolescents (54.5% female, ages 9-11 years at baseline) from the multisite, longitudinal Adolescent Brain Cognitive Development (ABCD) Study. An existing baseline STB history classification model was applied to predict longitudinal first-onset STB in adolescents compared with healthy controls and clinical controls (individuals with a mental health disorder but no STB). A new elastic net logistic regression model with 195 features was trained on data from 14 sites (n = 5,220), and the resulting top 15 features were validated at 7 independent sites (n = 2,283). RESULTS: The previously developed model to classify STB lifetime history also prospectively predicted first-onset STB in adolescents with an area under the curve (AUC) [95% CI] of 0.73 [0.70, 0.75], p < .001, compared with healthy controls and AUC [95% CI] of 0.63 [0.60, 0.66], p < .001, compared with clinical controls. The newly trained model with top 15 features performed similarly with AUC [95% CI] of 0.73 [0.71, 0.76], p < .001, and AUC [95% CI] of 0.64 [0.60, 0.66], p < .001, for the same comparison groups. The most consistent predictors across models included female sex, sleep disturbances, and maladaptive home and school environments. CONCLUSION: The models predicted first-onset STB in adolescents with moderate accuracy. This study also confirmed the roles of well-established psychological risk factors for STB and identified several novel neurocognitive and brain imaging risk factors. Future studies should validate these models in large-scale diverse samples before clinical translation. PLAIN LANGUAGE SUMMARY: This study followed over 7,500 adolescents for 4 years and tested 2 machine learning models using psychological, social, and brain data to identify those at risk of experiencing suicidal thoughts or behaviors. Both models predicted first-time suicidal thoughts or behaviors with moderate accuracy. Key risk factors that were identified included being female, experiencing sleep problems, and negative home and school environments. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Adolescent↗

PubMed1976

Stimulus duration as a measure of stimulus generalization.

Four pigeons in the line-positive group were trained with a vertical line on a green background that signalled intermittent reinforcement while a plain green field signalled extinction. Four pigeons in the line-negative group were trained with the opposite discrimination. Response to a control key terminated any trial and initiated the next trial. The birds also used the control key during generalization tests to control the durations of trials in which various line orientations were presented. These durations were summed to provide generalization gradients of stimulus duration that were positive or negative in accordance with the trained discriminations. In Experiment 2, birds from the line-positive group were tested with a procedure in which the control key was not available on some trials. This provided an independent assessment of response rates to the test stimuli. These rates were used to predict the stimulus durations obtained when the control key was available. The findings supported a general model for the prediction of response distributions among concurrent stimuli from rates observed with single stimuli.

Journal Article↗

PubMed2003

How predictive is grip force control in the complete absence of somatosensory feedback?

Grip force control relies on accurate internal models of the dynamics of our motor system and the external objects we manipulate. Internal models are not fixed entities, but rather are trained and updated by sensory experience. Sensory feedback signals relevant object properties and mechanical events, e.g. at the skin-object interface, to modify motor commands and update internal representations automatically. Here we prove that intact sensory feedback is essential for predictive grip force regulation. The efficiency and precision of grip force adjustments to load fluctuations arising from vertical and horizontal point-to-point arm movements with a hand-held object were analysed in a chronically deafferented subject (G.L.) and three healthy control subjects. Point-to-point movements started and ended with the object being held stationary. G.L. and healthy controls produced similar accelerations of the grasped object and consequently similar load magnitudes during vertical and horizontal movements. Compared with healthy controls, G.L. employed inefficiently high grip forces when holding and moving the object, indicating inaccurate force scaling to object weight and inertial loads. For healthy controls, the grip force profile was precisely timed to the movement-induced load fluctuations during vertical and horizontal movements. However, G.L.'s grip force profile was not processed to match differential loading requirements of movement direction. We conclude that predictive grip force control requires at least intermittent sensory feedback to signal the effectiveness of descending motor commands and to update internal models.

Adult↗

PubMed2003

From individual control to majority rule: extending transactional models of reproductive skew in animal societies.

Transactional concession models of social evolution explain the reproductive skew within groups by assuming that a dominant individual completely controls the allocation of reproduction to other group members. The models predict when the dominant will benefit from donating parcels of reproduction to other members in return for peaceful cooperation. Using linear programming methods, we present a 'majority-rules' model in which the summed actions of all society members, each with equal power, completely determine the reproductive share of any single member. The majority-rules model predicts that, despite the diffusion of power, a 'virtual dominant' (a dominant lacking special behavioural power) will emerge and that the reproductive skew will be exactly that predicted if the virtual dominant were to control completely the group's reproductive partitioning. The virtual dominant is the individual to which group members have the maximum average genetic relatedness. This result greatly broadens the applicability of transactional models of reproductive skew to social groups of any size, such as large-colony eusocial insects, and explains why queens in such colonies can achieve reproductive domination without any behavioural enforcement. Moreover, the majority-rules model unifies transactional-skew theory with models of worker policing and even generates a new theory for the cooperation among somatic cells in a multicellular organism.

Animals↗

PubMed1999

Predicting color from gray: the relationship between achromatic adjustment and asymmetric matching.

Achromatic adjustment has been used widely to study color context effects. In the achromatic adjustment procedure, an observer adjusts a test stimulus until it appears black, gray, or white. By its nature, achromatic adjustment directly measures the effect of context only for stimuli that appear gray. We present achromatic loci measured in two contexts and asymmetric color matches measured across the same two contexts. The results indicate that achromatic adjustments, together with a gain-control model, may be used to make accurate predictions of the chromaticity of asymmetric matches. Thus measurements of the effect of context for test stimuli that appear gray may be used to predict the effect of context for stimuli that appear colored. The experiments also indicate that accurate prediction depends on ensuring that observers use similar fixational strategies for the two judgments.

Adaptation, Physiological↗

PubMed1999

[Predictive factors of hospital admission in ambulatory surgery at a regional hospital].

BACKGROUND: Hospital admission following ambulatory surgery is a valid measure of morbidity and a quality indicator. To improve the efficiency of an ambulatory surgery unit it is essential to study the factors associated with unexpected hospital admission. Our goal was to analyze the association of age, ASA, type of surgical and anesthetic procedures, surgical duration, pain, vomiting and surgical and anesthetic complications with unexpected hospital admission. PATIENTS AND METHODS: Retrospective case-control study. The cases were all patients who underwent ambulatory surgery in the Viladecans Hospital (Barcelona, Spain) from October 1990 till May 1996 (n = 6,071), cases (n1 = 93), controls (n0 = 552). Logistic regression models with a predictive variable and multiple logistic regression were obtained. OR and 95% CI were calculated. RESULTS: Age was not significant for admission. ASA greater than status 1 (OR: 3.4 [1.4-9]); p = 0.01), the procto-perineo-sacrococcygeal procedures have significant risk (OR: 35 [4-304]; p < 0.00001), and other types of surgery were not significant. General, spinal anaesthesia and non-spinal locoregional ones with sedation were not significant (p > 0.2), but spinal anesthesia with deep sedation carried a significant risk (OR: 20 [3-122]; p < 0.00001). Surgical duration higher than 40 min (OR: 22 [5-94]; p < 0.00001), pain (OR: 12 [3-55]; p < 0.00001) and vomiting (OR: 8.5 [1.2-59]; p = 0.03) were significant factors in predicting hospital admission. CONCLUSIONS: The factors related with unexpected hospital admission following ambulatory surgery were: surgical and anesthetic complications, pain, procto-perineal and sacrococcigeal procedures, spinal anesthesia with profound sedation and a surgical duration time higher than 40 min.

Adolescent↗

PubMed2002

Predictive model to identify positive tuberculosis skin test results during contact investigations.

CONTEXT: Budgetary constraints in tuberculosis (TB) control programs require streamlining contact investigations without sacrificing disease control. OBJECTIVE: To develop more efficient methods of TB contact investigation by creating a model of TB transmission using variables that best predict a positive tuberculin skin test among contacts of an active TB case. DESIGN, SETTING, AND SUBJECTS: After standardizing the interview and documentation process, data were collected on 292 consecutive TB cases and their 2941 contacts identified by the Alabama Department of Public Health between January and October 1998. Generalized estimating equations were used to create a model for predicting positive skin test results in contacts of active TB cases. The model was then validated using data from a prospective cohort of 366 new TB cases and their 3162 contacts identified between October 1998 and April 2000. MAIN OUTCOME MEASURE: Tuberculin skin test result. RESULTS: Using generalized estimating equations to build a predictive model, 7 variables were found to significantly predict a positive tuberculin skin test result among contacts of an active TB case. Further testing showed this model to have a sensitivity, specificity, and positive predictive value of approximately 89%, 36%, and 26%, respectively. The false-negative rate was less than 10%, and about 40% of the contact workload could be eliminated using this model. CONCLUSIONS: Certain characteristics can be used to predict contacts most likely to have a positive tuberculin skin test result. Use of such models can significantly reduce the number of contacts that public health officials need to investigate while still maintaining excellent disease control.

Adolescent↗

PubMed1989

[Congenital malformations: a model predictive based on risk factors].

Several risk factors were studied in regard to congenital malformations. Malformed newborns (n = 1200) and controls (n = 1200) seen at the Universidad de Chile Hospital between 1969 and 1979 were examined. Their mothers were asked about possible risk factors. Parenteral age and birth order was significantly higher for malformed newborns than for controls. A family history of congenital malformations was more frequent in malformed newborns. Infertility, metrorrhagia and maternal diseases during pregnancy were more frequent in malformed newborns than in controls. A function that discriminates between controls mothers and mothers of malformed newborns was obtained by a logistic regression model. This function correctly predicted 65% of cases.

Congenital Abnormalities↗

PubMed1996

A linear quadratic analysis of gynaecological brachytherapy.

Four hundred and fourteen patients were treated by radical radiotherapy alone for cervical carcinoma at the Western Infirmary and the Royal Beatson Memorial Hospital between April 1982 and December 1987. All patients received external beam radiotherapy in addition to brachytherapy, using either manually inserted caesium (n = 107) or the Selectron afterloading machine (n = 307). Three mean Selectron dose rates were used: 0.91 Gy/h, 1.195 Gy/h and 1.74 Gy/h. During this period of time, the cumulative radiation effect formula was used to calculate an overall brachytherapy dose reduction to compensate for the increase in point 'A' dose rate. We have compared the local control rates and the incidence of late effects seen in these patients with theoretical parameters calculated using the linear quadratic (LQ) model. This model predicts a small rise in late effects as the dose rate increases, which is also seen in clinical practice; it also predicts a reduction in local control, partially offset by the addition of external beam radiotherapy, which would be most marked for early stage disease. There was a small fall in local control associated with Selectron treatment, but of a smaller size than predicted by the LQ model.

Algorithms↗

PubMedDate not supplied

Comparative evaluation of the use of artificial neural networks for modelling the epidemiology of schistosomiasis mansoni.

There has been a marked increase in the application of approaches based on artificial intelligence (AI) in the field of computer science and medical diagnosis, but AI is still relatively unused in epidemiological settings. In this study we report results of the application of neural networks (NN; a special category of AI) to schistosomiasis. It was possible to design an NN structure which can process and fit epidemiological data collected from 251 schoolchildren in Egypt using the first year's data to predict second and third years' infection rates. Data collected over 3 years included age, gender, exposure to canal water and agricultural activities, medical history and examination, and stool and urine parasitology. Schistosoma mansoni infection rates were 50%, 78% and 66% at the baseline and the 2 follow-up periods, respectively. NN modelling was based on the standard back-propagation algorithm, in which we built a suitable configuration of the network, using the first year's data, that optimized performance. It was implemented on an IBM compatible computer using commercially available software. The performance of the NN model in the first year compared favourably with logistic regression (NN sensitivity = 83% (95% confidence interval [CI] 78-88%) and positive predictive value (PPV) = 63% (95% CI 57-69%); logistic regression sensitivity = 66% (95% CI 60%-72%) and PPV = 59% (95% CI 53%-65%). The NN model generalized the criteria for predicting infection over time better than logistic regression and showed more stability over time, as it retained its sensitivity and specificity and had better false positive and negative profiles than logistic regression. The potential of NN-based models to analyse and predict wide-scale control programme data, which are inevitably based on unstable egg excretion rates and insensitive laboratory techniques, is promising but still untapped.

Adolescent↗

PubMedDate not supplied

Cost of AIDS care in Mexico: what are its main individual predictors?

BACKGROUND: The Mexican government is offering universal access to antiretroviral (ARV) drugs. The cost of doing so, despite aggressive price negotiation with the pharmaceutical industry, remains high. Even with a low prevalence, about 150,000 Mexicans are estimated to be living with HIV and will require ARV treatment. Estimating the resources needed to fund this gap should consider how patient and provider characteristics affect health care costs. METHODS: Using a sample of patients from 11 facilities in three Mexican cities representing a large proportion of AIDS patients in the country, we developed a fixed-effect model, which by controlling the facilities and individual heterogeneity estimates predicted costs using patient demographic and socioeconomic characteristics as well as physician training. RESULTS: The estimated model explains about 45% of the variation in costs. Additional education is significantly and positively associated with cost. Increasing age is also associated with higher costs. CONCLUSIONS: Socioeconomic status and demographic characteristics explain an important proportion of variation in care costs for AIDS, despite AIDS being such a heterogeneous disease. Such characteristics will need to be taken into account when resource needs are estimated. A priority-setting process considering the principles of equity in the fair distribution of resources is needed to help reduce the social burden of HIV/AIDS in Mexico.

Acquired Immunodeficiency Syndrome↗

PubMed2002

The wall-thinning to transmitral flow-velocity relation: derivation with in vivo validation.

Motion of the endocardial surface in diastole is the resultant effect of wall thinning. Endocardial wall motion to transmitral flow (Doppler E-wave) relations that predict wall thinning are derived using conservation of myocardial volume, two simplified (spatiotemporally homogeneous) left ventricular (LV) geometric models and the constant-volume pump attribute of the heart. For validation, model-predicted vs. color M-mode recorded maximum rate of wall thinning was compared in (n = 15) normal controls. Excellent agreement for both models (r = 0.84, r = 0.86) was observed. For abnormal LV function (n = 15), model-predicted vs. M-mode recorded maximum rate of wall-thinning correlated poorly (r = -0.28, r = -0.22). We conclude that, in normal ventricles, the Doppler E-wave and wall thinning are related through the constant-volume attribute of the heart and its geometry. Pathologic cases are governed by the same principles, but the filling to wall-thinning relation is altered by spatiotemporal inhomogeneities in geometry and wall motion.

Adult↗