Biology subjects

Duarte, R.

Publications and source records attributed to Duarte, R..

3 recordsLinked to original sources

bioRxiv2018

Introducing risk inequality metrics in tuberculosis policy development

Global stakeholders including the World Health Organization rely on predictive models for developing strategies and setting targets for tuberculosis care and control programs. Failure to account for variation in individual risk leads to substantial biases that impair data interpretation and policy decisions1,2. Anticipated impediments to estimating heterogeneity for each parameter are discouraging despite considerable technical progress in recent years. Here we identify acquisition of infection as the single process where heterogeneity most fundamentally impacts model outputs, due to cohort selection imposed by dynamic forces of infection. Individuals with higher risk of acquiring infection are predominantly affected by the pathogen, leaving the unaffected pool with those whose intrinsic risk is lower. This causes susceptibility pools to attain average risks which are lower under higher forces of infection. Interventions that modify the force of infection change the strength of selection, and therefore alter average risks in the pools which feed further incidence. Inability to account for these dynamics is what makes homogenous models unsuitable. We introduce concrete metrics to approximate risk inequality in tuberculosis, demonstrate their utility in mathematical models, and pack the information into a risk inequality coefficient which can be calculated and reported by national tuberculosis programs for use in policy development and modeling.

epidemiology↗

bioRxiv2018

Using High Throughput DNA Sequencing to Evaluate the Accuracy of Serial Dilution Based Tests of Microbial Activities in Oil Pipelines

Microbial activities have detrimental effects on industrial infrastructure. If not controlled, microbial presence can result in corrosion, biofilm formation, and product degradation. Serial dilution tests are routinely used for evaluating presence and abundance of microorganisms by diluting samples and culturing microbes in specific media designed to support microorganisms with particular properties, such as sulfate reduction.\n\nA high-throughput sequencing approach was used to evaluate changes in microbial composition during four standard serial dilution tests. Analysis of 159 isolates revealed significant differences in the microbial compositions of sequential serial dilution titers and identified several cases where: (a) bacteria known to have a detrimental metabolic function (such as acid production) were lost in the serial dilution medium designed to test for this function; (b) bacteria virtually absent in the original sample became dominant in the serial dilution medium. These observations raise concerns regarding the accuracy and overall usefulness of serial dilution tests.

microbiology↗

bioRxiv2017

Leveraging heterogeneity for neural computation with fading memory in layer 2/3 cortical microcircuits

Complexity and heterogeneity are intrinsic to neurobiological systems, manifest in every process, at every scale, and are inextricably linked to the systems emergent collective behaviours and function. However, the majority of studies addressing the dynamics and computational properties of biologically inspired cortical microcircuits tend to assume (often for the sake of analytical tractability) a great degree of homogeneity in both neuronal and synaptic/connectivity parameters. While simplification and reductionism are necessary to understand the brains functional principles, disregarding the existence of the multiple heterogeneities in the cortical composition, which may be at the core of its computational proficiency, will inevitably fail to account for important phenomena and limit the scope and generalizability of cortical models. We address these issues by studying the individual and composite functional roles of heterogeneities in neuronal, synaptic and structural properties in a biophysically plausible layer 2/3 microcircuit model, built and constrained by multiple sources of empirical data. This approach was made possible by the emergence of large-scale, well curated databases, as well as the substantial improvements in experimental methodologies achieved over the last few years. Our results show that variability in single neuron parameters is the dominant source of functional specialization, leading to highly proficient microcircuits with much higher computational power than their homogeneous counterparts. We further show that fully heterogeneous circuits, which are closest to the biophysical reality, owe their response properties to the differential contribution of different sources of heterogeneity.

neuroscience↗