The COVID-19 pandemic has affected cities particularly hard. Here, we provide an in-depth characterization of disease incidence and mortality and their dependence on demographic and socioeconomic ...strata in Santiago, a highly segregated city and the capital of Chile. Our analyses show a strong association between socioeconomic status and both COVID-19 outcomes and public health capacity. People living in municipalities with low socioeconomic status did not reduce their mobility during lockdowns as much as those in more affluent municipalities. Testing volumes may have been insufficient early in the pandemic in those places, and both test positivity rates and testing delays were much higher. We find a strong association between socioeconomic status and mortality, measured by either COVID-19-attributed deaths or excess deaths. Finally, we show that infection fatality rates in young people are higher in low-income municipalities. Together, these results highlight the critical consequences of socioeconomic inequalities on health outcomes.
Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic ...atlas of landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that resolves all neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. We showcase three applications that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding for these stimuli.
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•NeuroPAL: a strain with a stereotyped fluorescent color map to identify all neurons•NeuroPAL and semi-automated ID software pinpoint patterns of reporter gene expression•NeuroPAL identifies neuronal differentiation defects in mutant backgrounds•Dynamic whole-brain neuronal activity patterns defined by NeuroPAL in combination with GCaMP
The multicolor transgene NeuroPAL allows for nervous-system-wide neuronal identification in C. elegans using a combination of reporters and colors to generate an invariant color map across individuals and is compatible with reporters for gene expression and neuronal activity.
Simultaneous electrical stimulation and recording using multi-electrode arrays can provide a valuable technique for studying circuit connectivity and engineering neural interfaces. However, ...interpreting these measurements is challenging because the spike sorting process (identifying and segregating action potentials arising from different neurons) is greatly complicated by electrical stimulation artifacts across the array, which can exhibit complex and nonlinear waveforms, and overlap temporarily with evoked spikes. Here we develop a scalable algorithm based on a structured Gaussian Process model to estimate the artifact and identify evoked spikes. The effectiveness of our methods is demonstrated in both real and simulated 512-electrode recordings in the peripheral primate retina with single-electrode and several types of multi-electrode stimulation. We establish small error rates in the identification of evoked spikes, with a computational complexity that is compatible with real-time data analysis. This technology may be helpful in the design of future high-resolution sensory prostheses based on tailored stimulation (e.g., retinal prostheses), and for closed-loop neural stimulation at a much larger scale than currently possible.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SARS-CoV-2 vaccines have been distributed at unprecedented speed. Still, little is known about temporal vaccination trends, their association with socioeconomic inequality, and their consequences for ...disease control. Using data from 161 countries/territories and 58 states, we examined vaccination rates across high and low socioeconomic status (SES), showing that disparities in coverage exist at national and subnational levels. We also identified two distinct vaccination trends: a rapid initial rollout, quickly reaching a plateau, or sigmoidal and slow to begin. Informed by these patterns, we implemented an SES-stratified mechanistic model, finding profound differences in mortality and incidence across these two vaccination types. Timing of initial rollout affects disease outcomes more substantially than final coverage or degree of SES disparity. Unexpectedly, timing is not associated with wealth inequality or GDP per capita. While socioeconomic disparity should be addressed, accelerating initial rollout for all over focusing on increasing coverage is an accessible intervention that could minimize the burden of disease across socioeconomic groups.
Modern neurotechnologies enable the recording of neural activity at the scale of entire brains and with single-cell resolution. However, the lack of principled approaches to extract structure from ...these massive data streams prevent us from fully exploiting the potential of these technologies. This thesis, divided in three parts, introduces new statistical machine learning methods to enable the large-scale analysis of some of these complex neural datasets. In the first part, I present a method that leverages Gaussian quadrature to accelerate inference of neural encoding models from a certain type of observed neural point processes — spike trains — resulting in substantial improvements over existing methods. The second part focuses on the simultaneous electrical stimulation and recording of neurons using large electrode arrays. There, identification of neural activity is hindered by stimulation artifacts that are much larger than spikes, and overlap temporally with spikes. To surmount this challenge, I develop an algorithm to infer and cancel this artifact, enabling inference of the neural signal of interest. This algorithm is based on a a bayesian generative model for recordings, where a structured gaussian process is used to represent prior knowledge of the artifact. The algorithm achieves near perfect accuracy and enables the analysis of data hundreds of time faster than previous approaches. The third part is motivated by the problem of inference of neural dynamics in the worm C.elegans: when taking a data-driven approach to this question, e.g., when using whole-brain calcium imaging data, one is faced with the need to match neural recordings to canonical neural identities, in practice resolved by tedious human labor. Alternatively, on a bayesian setup this problem may be cast as posterior inference of a latent permutation. I introduce methods that enable gradient-based approximate posterior inference of permutations, overcoming the difficulties imposed by the combinatorial and discrete nature of this object. Results suggest the feasibility of automating neural identification, and demonstrate variational inference in permutations is a sensible alternative to MCMC.
Many matching, tracking, sorting, and ranking problems require probabilistic reasoning about possible permutations, a set that grows factorially with dimension. Combinatorial optimization algorithms ...may enable efficient point estimation, but fully Bayesian inference poses a severe challenge in this high-dimensional, discrete space. To surmount this challenge, we start with the usual step of relaxing a discrete set (here, of permutation matrices) to its convex hull, which here is the Birkhoff polytope: the set of all doubly-stochastic matrices. We then introduce two novel transformations: first, an invertible and differentiable stick-breaking procedure that maps unconstrained space to the Birkhoff polytope; second, a map that rounds points toward the vertices of the polytope. Both transformations include a temperature parameter that, in the limit, concentrates the densities on permutation matrices. We then exploit these transformations and reparameterization gradients to introduce variational inference over permutation matrices, and we demonstrate its utility in a series of experiments.
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