A Likelihood-Free Inference Framework for Population Genetic Data using Exchangeable Neural Networks

An explosion of high-throughput DNA sequencing in the past decade has led to a surge of interest in population-scale inference with whole-genome data. Recent work in population genetics has centered on designing inference methods for relatively simple model classes, and few scalable general-purpose inference techniques exist for more realistic, complex models. To achieve this, two inferential challenges need to be addressed: (1) population data are exchangeable, calling for methods that efficiently exploit the symmetries of the data, and (2) computing likelihoods is intractable as it requires integrating over a set of correlated, extremely high-dimensional latent variables. These challenges are traditionally tackled by likelihood-free methods that use scientific simulators to generate datasets and reduce them to hand-designed, permutation-invariant summary statistics, often leading to inaccurate inference. In this work, we develop an exchangeable neural network that performs summary statistic-free, likelihood-free inference. Our framework can be applied in a black-box fashion across a variety of simulation-based tasks, both within and outside biology. We demonstrate the power of our approach on the recombination hotspot testing problem, outperforming the state-of-the-art.Comment: 9 pages, 8 figure

Cost-Effectiveness of Radiofrequency Catheter Ablation for Atrial Fibrillation

ObjectivesWe sought to compare the cost-effectiveness of left atrial catheter ablation (LACA), amiodarone, and rate control therapy in the management of atrial fibrillation (AF).BackgroundLeft atrial catheter ablation has been performed to eliminate AF, but its cost-effectiveness is unknown.MethodsWe developed a decision-analytic model to evaluate the cost-effectiveness of LACA in 55- and 65-year-old cohorts with AF at moderate and low stroke risk. Costs, health utilities, and transition probabilities were derived from published literature and Medicare data. We performed primary threshold analyses to determine the minimum level of LACA efficacy and stroke risk reduction needed to make LACA cost-effective at $50,000 and$100,000 per quality-adjusted life-year (QALY) thresholds.ResultsIn 65-year-old subjects with AF at moderate stroke risk, relative reduction in stroke risk with an 80% LACA efficacy rate for sinus rhythm restoration would need to be ≥42% and ≥11% to yield incremental cost-effectiveness ratios (ICERs) <$50,000 and$100,000 per QALY, respectively. Higher and lower LACA efficacy rates would require correspondingly lower and higher stroke risk reduction for equivalent ICER thresholds. In the 55-year-old moderate stroke risk cohort, lower LACA efficacy rates or stroke risk reduction would be needed for the same ICER thresholds. In patients at low stroke risk, LACA was unlikely to be cost-effective.ConclusionsThe use of LACA may be cost-effective in patients with AF at moderate risk for stroke, but it is not cost-effective in low-risk patients. Our threshold analyses may provide a framework for the design of future clinical trials by providing effect size estimates for LACA efficacy needed

An Integrated Content and Metadata based Retrieval System for Art

In this paper we describe aspects of the Artiste project to develop a distributed content and metadata based analysis, retrieval and navigation system for a number of major European Museums. In particular, after a brief overview of the complete system, we describe the design and evaluation of some of the image analysis algorithms developed to meet the specific requirements of the users from the museums. These include a method for retrievals based on sub images, retrievals based on very low quality images and retrieval using craquelure type

A Note on Warped String Compactification

We give a short review of a large class of warped string geometries, obtained via F-theory compactified on Calabi-Yau fourfolds, that upon reduction to 5 dimensions give consistent supersymmetric realizations of the RS compactification scenario.Comment: 11 pages, 3 figures; v3 corrected spelling of Calab

Photooxidation of 2-methyl-3-buten-2-ol (MBO) as a potential source of secondary organic aerosol

2-Methyl-3-buten-2-ol (MBO) is an important biogenic hydrocarbon emitted in large quantities by pine forests. Atmospheric photooxidation of MBO is known to lead to oxygenated compounds, such as glycolaldehyde, which is the precursor to glyoxal. Recent studies have shown that the reactive uptake of glyoxal onto aqueous particles can lead to formation of secondary organic aerosol (SOA). In this work, MBO photooxidation under high- and low-NO_x conditions was performed in dual laboratory chambers to quantify the yield of glyoxal and investigate the potential for SOA formation. The yields of glycolaldehyde and 2-hydroxy-2-methylpropanal (HMPR), fragmentation products of MBO photooxidation, were observed to be lower at lower NO_x concentrations. Overall, the glyoxal yield from MBO photooxidation was 25% under high-NO_x and 4% under low-NO_x conditions. In the presence of wet ammonium sulfate seed and under high-NO_x conditions, glyoxal uptake and SOA formation were not observed conclusively, due to relatively low (<30 ppb) glyoxal concentrations. Slight aerosol formation was observed under low-NO_x and dry conditions, with aerosol mass yields on the order of 0.1%. The small amount of SOA was not related to glyoxal uptake, but is likely a result of reactions similar to those that generate isoprene SOA under low-NO_x conditions. The difference in aerosol yields between MBO and isoprene photooxidation under low-NO_x conditions is consistent with the difference in vapor pressures between triols (from MBO) and tetrols (from isoprene). Despite its structural similarity to isoprene, photooxidation of MBO is not expected to make a significant contribution to SOA formation

Isospin splitting in heavy baryons and mesons

A recent general analysis of light-baryon isospin splittings is updated and extended to charmed baryons. The measured $\Sigma_c$ and $\Xi_c$ splittings stand out as being difficult to understand in terms of two-body forces alone. We also discuss heavy-light mesons; though the framework here is necessarily less general, we nevertheless obtain some predictions that are not strongly model-dependent.Comment: 12 pages REVTEX 3, plus 4 uuencoded ps figures, CMU-HEP93-

Long-term use of antibiotics and risk of colorectal adenoma

Objective—Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated. Design—We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results—We documented 1,195 cases of adenoma. Increasing duration of antibiotic use at age 20–39 (Ptrend=0.002) and 40–59 (Ptrend=0.001) was significantly associated with an increased risk of colorectal adenoma. Compared to non-users, women who used antibiotics for ≥2 months between age 20–39 had a multivariable OR of 1.36 (95% CI: 1.03–1.79). Women who used ≥2 months of antibiotics between age 40–59 had a multivariable OR of 1.69 (95% CI: 1.24–2.31). The associations were similar for low-risk vs. high-risk adenomas (size ≥1 cm, or with tubulovillous/villous histology, or ≥3 detected lesions), but appeared modestly stronger for proximal compared with distal adenomas. In contrast, recent antibiotic use within the past 4 years was not associated with risk of adenoma (Ptrend=0.44). Conclusions—Long-term antibiotic use in early to middle adulthood was associated with increased risk of colorectal adenoma