Biphasic pattern in the effect of severe measles infection; the difference between additive and multiplicative scale.
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ABSTRACT:
SUBMITTER: Le NTH
PROVIDER: S-EPMC8670196 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events.MethodsThe effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery.ResultsThe multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70.ConclusionsThe present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification.
| S-EPMC4821587 | biostudies-literature
Project description:Additive and multiplicative regression models of habituation were compared regarding the fit to looking times from a habituation experiment with infants aged between 3 and 11 months. In contrast to earlier studies, the current study considered multiple probability distributions, namely Weibull, gamma, lognormal and normal distribution. In the habituation experiment the type of contrast between the habituation and the test trial was varied (luminance, color or orientation contrast), crossed with the number of habituation trials (1, 3, 5, or 7 habituation trials) and crossed with three age cohorts (4, 7, 10 months). The initial mean LT to dark stimuli (around 3.7 s) was considerably shorter than the mean LT to green and gray stimuli (around 5 s). Infants showed the strongest dishabituation to changes from dark to bright (luminance contrast) and weak-to-no dishabituation to a 90-degrees rotation of the gray stimuli (orientation contrast). The dishabituation was stronger after five and seven habituation trials, but the result was not statistically robust. The gamma distribution showed the best fit in terms of log-likelihood and mean absolute error and the best predictive performance. Furthermore, the gamma distribution showed small correlations between parameters relative to other models. The normal additive model showed an inferior fit and medium correlations between the parameters. In particular, the positive correlation between the initial looking time (LT) and the habituation rate was likely responsible for a different interpretation relative to the multiplicative models of the main effect of age on the habituation rate. Otherwise, the additive and multiplicative models provided similar statistical conclusions. The performance of the model versions without pooling and with partial pooling across participants (also called random-effects, multi-level or hierarchical models) were compared. The latter type of models showed worse data fit but more precise predictions and reduced correlations between the parameters. The performance of model variants with auto-regressive time structures were explored but showed considerably worse fit. The performance of quadratic models that allowed non-monotonic changes in LTs were investigated as well. However, when fitted with LT data, these models did not produce non-monotonic change in LTs. The study underscores the utility of partial-pooling models in terms of providing more accurate predictions. Further, it agrees with previous research in that a multiplicative LT model is preferable. Nevertheless, the current results suggest that the impact of the choice of an additive model on the statistical inference is less dramatic then previously assumed.
| S-EPMC8286709 | biostudies-literature
Project description:BackgroundIn survival analysis, data can be modeled using either a multiplicative hazards regression model (such as the Cox model) or an additive hazards regression model (such as Lin's or Aalen's model). While several diagnostic tools are available to check the assumptions underpinning each type of model, there is no defined procedure to fit these models optimally. Moreover, the two types of models are rarely combined in survival analysis. Here, we propose a strategy for optimal fitting of multiplicative and additive hazards regression models in survival analysis.MethodsThis section details our proposed strategy for optimal fitting of multiplicative and additive hazards regression models, with a focus on the assumptions underpinning each type of model, the diagnostic tools used to check these assumptions, and the steps followed to fit the data. The proposed strategy draws on classical diagnostic tools (Schoenfeld and martingale residuals) and less common tools (pseudo-observations, martingale residual processes, and Arjas plots).ResultsThe proposed strategy is applied to a dataset of patients with myocardial infarction (TRACE data frame). The effects of 5 covariates (age, sex, diabetes, ventricular fibrillation, and clinical heart failure) on the hazard of death are analyzed using multiplicative and additive hazards regression models. The proposed strategy is shown to fit the data optimally.ConclusionsSurvival analysis is improved by using multiplicative and additive hazards regression models together, but specific steps must be followed to fit the data optimally. By providing different measures of the same effect, our proposed strategy allows for better interpretation of the data.
| S-EPMC8101173 | biostudies-literature
Project description:Numerous studies have shown that neuronal responses are modulated by stimulus properties and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation and vice versa. The information encoded by multiplicatively modulated neurons increased with greater population activity, while that of additively modulated neurons decreased. These effects offset each other so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a "traffic light" that determines which subset of neurons is most informative.
| S-EPMC5129626 | biostudies-other
Project description:In this paper, the influence of measurement errors in exposure doses in a regression model with binary response is studied. Recently, it has been recognized that uncertainty in exposure dose is characterized by errors of two types: classical additive errors and Berkson multiplicative errors. The combination of classical additive and Berkson multiplicative errors has not been considered in the literature previously. In a simulation study based on data from radio-epidemiological research of thyroid cancer in Ukraine caused by the Chornobyl accident, it is shown that ignoring measurement errors in doses leads to overestimation of background prevalence and underestimation of excess relative risk. In the work, several methods to reduce these biases are proposed. They are new regression calibration, an additive version of efficient SIMEX, and novel corrected score methods.
| S-EPMC4915607 | biostudies-literature
Project description:BackgroundPredictive microbiology develops mathematical models that can predict the growth rate of a microorganism population under a set of environmental conditions. Many primary growth models have been proposed. However, when primary models are applied to bacterial growth curves, the biological variability is reduced to a single curve defined by some kinetic parameters (lag time and growth rate), and sometimes the models give poor fits in some regions of the curve. The development of a prediction band (from a set of bacterial growth curves) using non-parametric and bootstrap methods permits to overcome that problem and include the biological variability of the microorganism into the modelling process.ResultsAbsorbance data from Listeria monocytogenes cultured at 22, 26, 38, and 42 degrees C were selected under different environmental conditions of pH (4.5, 5.5, 6.5, and 7.4) and percentage of NaCl (2.5, 3.5, 4.5, and 5.5). Transformation of absorbance data to viable count data was carried out. A random effect multiplicative heteroscedastic model was considered to explain the dynamics of bacterial growth. The concept of a prediction band for microbial growth is proposed. The bootstrap method was used to obtain resamples from this model. An iterative procedure is proposed to overcome the computer intensive task of calculating simultaneous prediction intervals, along time, for bacterial growth. The bands were narrower below the inflection point (0-8 h at 22 degrees C, and 0-5.5 h at 42 degrees C), and wider to the right of it (from 9 h onwards at 22 degrees C, and from 7 h onwards at 42 degrees C). A wider band was observed at 42 degrees C than at 22 degrees C when the curves reach their upper asymptote. Similar bands have been obtained for 26 and 38 degrees C.ConclusionsThe combination of nonparametric models and bootstrap techniques results in a good procedure to obtain reliable prediction bands in this context. Moreover, the new iterative algorithm proposed in this paper allows one to achieve exactly the prefixed coverage probability for the prediction band. The microbial growth bands reflect the influence of the different environmental conditions on the microorganism behaviour, helping in the interpretation of the biological meaning of the growth curves obtained experimentally.
| S-EPMC2829529 | biostudies-literature
Project description:Many day-to-day decisions may involve risky outcomes that occur at some delay after a decision has been made. We refer to such scenarios as delayed lotteries. Despite human choice often involves delayed lotteries, past research has primarily focused on decisions with delayed or risky outcomes. Comparatively, less research has explored how delay and probability interact to influence decisions. Within research on delayed lotteries, rigorous comparisons of models that describe choice from the discounting framework have not been conducted. We performed two experiments to determine how gain or loss outcomes are devalued when delayed and risky. Experiment 1 used delay and probability ranges similar to past research on delayed lotteries. Experiment 2 used individually calibrated delay and probability ranges. Ten discounting models were fit to the data using a genetic algorithm. Candidate models were derived from past research on discounting delayed or probabilistic outcomes. We found that participants' behavior was best described primarily by a three-parameter multiplicative model. Measures based on information criteria pointed to a solution in which only delay and probability were psychophysically scaled. Absolute measures based on residuals pointed to a solution in which amount, delay, and probability are simultaneously scaled. Our research suggests that separate scaling parameters for different discounting factors may not be necessary with delayed lotteries.
| S-EPMC7244164 | biostudies-literature
Project description:Understanding the genetic background of complex diseases requires the expansion of studies beyond univariate associations. Therefore, it is important to use interaction assessments of risk factors in order to discover whether, and how genetic risk variants act together on disease development. The principle of interaction analysis is to explore the magnitude of the combined effect of risk factors on disease causation. In this study, we use simulations to investigate different scenarios of causation to show how the magnitude of the effect of two risk factors interact. We mainly focus on the two most commonly used interaction models, the additive and multiplicative risk scales, since there is often confusion regarding their use and interpretation. Our results show that the combined effect is multiplicative when two risk factors are involved in the same chain of events, an interaction called synergism. Synergism is often described as a deviation from additivity, which is a broader term. Our results also confirm that it is often relevant to estimate additive effect relationships, because they correspond to independent risk factors at low disease prevalence. Importantly, we evaluate the threshold of more than two required risk factors for disease causation, called the multifactorial threshold model. We found a simple mathematical relationship (square root) between the threshold and an additive-to-multiplicative linear effect scale (AMLES), where 0 corresponds to an additive effect and 1 to a multiplicative. We propose AMLES as a metric that could be used to test different effects relationships at the same time, given that it can simultaneously reveal additive, multiplicative and intermediate risk effects relationships. Finally, the utility of our simulation study was demonstrated using real data by analyzing and interpreting gene-gene interaction odds ratios from a rheumatoid arthritis case-control cohort.
| S-EPMC8075235 | biostudies-literature
Project description:The combined quantum mechanical (QM) and molecular mechanical (MM) approach (QM/MM) is a popular method to study reactions in biochemical macromolecules. Even if the general procedure of using QM for a small, but interesting part of the system and MM for the rest is common to all approaches, the details of the implementations vary extensively, especially the treatment of the interface between the two systems. For example, QM/MM can use either additive or subtractive schemes, of which the former is often said to be preferable, although the two schemes are often mixed up with mechanical and electrostatic embedding. In this article, we clarify the similarities and differences of the two approaches. We show that inherently, the two approaches should be identical and in practice require the same sets of parameters. However, the subtractive scheme provides an opportunity to correct errors introduced by the truncation of the QM system, i.e., the link atoms, but such corrections require additional MM parameters for the QM system. We describe and test three types of link-atom correction, viz. for van der Waals, electrostatic, and bonded interactions. The calculations show that electrostatic and bonded link-atom corrections often give rise to problems in the geometries and energies. The van der Waals link-atom corrections are quite small and give results similar to a pure additive QM/MM scheme. Therefore, both approaches can be recommended.
| S-EPMC5891596 | biostudies-literature
Project description:The Streptococcus pneumoniae pilus-1 is encoded by pilus islet 1 (PI-1), which has three clonal variants (clade I, II and III) and is present in about 30% of clinical pneumococcal isolates. In vitro and in vivo assays have demonstrated that pilus-1 is involved in attachment to epithelial cells and virulence, as well as protection in mouse models of infection. Several reports suggest that pilus-1 expression is tightly regulated and involves the interplay of numerous genetic regulators, including the PI-1 positive regulator RlrA. In this report we provide evidence that pilus expression, when analyzed at the single-cell level in PI-1 positive strains, is biphasic. In fact, the strains present two phenotypically different sub-populations of bacteria, one that expresses the pilus, while the other does not. The proportions of these two phenotypes are variable among the strains tested and are not influenced by genotype, serotype, growth conditions, colony morphology or by the presence of antibodies directed toward the pilus components. Two sub-populations, enriched in pilus expressing or not expressing bacteria were obtained by means of colony selection and immuno-detection methods for five strains. PI-1 sequencing in the two sub-populations revealed the absence of mutations, thus indicating that the biphasic expression observed is not due to a genetic modification within PI-1. Microarray expression profile and western blot analyses on whole bacterial lysates performed comparing the two enriched sub-populations, revealed that pilus expression is regulated at the transcriptional level (on/off regulation), and that there are no other genes, in addition to those encoded by PI-1, concurrently regulated across the strains tested. Finally, we provide evidence that the over-expression of the RrlA positive regulator is sufficient to induce pilus expression in pilus-1 negative bacteria. Overall, the data presented here suggest that the observed biphasic pilus expression phenotype could be an example of bistability in pneumococcus.
| S-EPMC3120856 | biostudies-literature