Longitudinal LASSO: Jointly Learning Features and Temporal Contingency for Outcome Prediction

Longitudinal analysis is important in many disciplines, such as the study of behavioral transitions in social science. Only very recently, feature selection has drawn adequate attention in the context of longitudinal modeling. Standard techniques, such as generalized estimating equations, have been modified to select features by imposing sparsity-inducing regularizers. However, they do not explicitly model how a dependent variable relies on features measured at proximal time points. Recent graphical Granger modeling can select features in lagged time points but ignores the temporal correlations within an individual's repeated measurements. We propose an approach to automatically and simultaneously determine both the relevant features and the relevant temporal points that impact the current outcome of the dependent variable. Meanwhile, the proposed model takes into account the non-{\em i.i.d} nature of the data by estimating the within-individual correlations. This approach decomposes model parameters into a summation of two components and imposes separate block-wise LASSO penalties to each component when building a linear model in terms of the past $\tau$ measurements of features. One component is used to select features whereas the other is used to select temporal contingent points. An accelerated gradient descent algorithm is developed to efficiently solve the related optimization problem with detailed convergence analysis and asymptotic analysis. Computational results on both synthetic and real world problems demonstrate the superior performance of the proposed approach over existing techniques.Comment: Proceedings of the 21th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. ACM, 201

Cholera outbreak in districts around Lake Chilwa, Malawi: Lessons learned

BackgroundCholera is endemic in Malawi with seasonal outbreaks during the wet season. People living around Lake Chilwa rely on the lake for their water supply. From May 2009 to May 2010, a cholera outbreak occurred in fishing communities around Lake Chilwa. This paper describes the outbreak response and lessons learned for prevention and management of future outbreaks.MethodsStarting in January 2010, Médecins Sans Frontières (MSF) helped District Health Management Teams (DHMTs) to distribute educational materials, water disinfectant and hygiene supplies, and oral rehydration solution (ORS) in fishing communities. MSF also supported case management by mentoring health workers and providing equipment and supplies.ResultsA total of 1,171 cholera cases and 21 deaths were reported in the districts around the lake, with cases also being reported on the Mozambican side of the lake. The attack rate was highest among people living on or around the lake, particularly among fishermen. Samples of lake water had high turbidity conducive to the propagation of Vibrio cholerae.ConclusionA number of practical measures could be taken to prevent future outbreaks and to manage outbreaks more effectively. These measures should address surveillance, environmental management, outbreak preparedness, and case management

CD4 testing at clinics to assess eligibility for Antiretroviral therapy

BackgroundIn 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from <250 cells/μl and <350 cells/μl, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART.Methods:We abstracted CD4 counts of all ART-naïve, HIV-infected patients with WHO clinical stages 1 and 2 and an initial CD4 test between May 2008 and June 2009. At four clinics, we also abstracted CD4 counts of patients not initially eligible for ART who were retested before April 2010.ResultsOf 1,113 patients tested, the initial CD4 was “≤250 cells/μl” and “≤350 cells/μl” in 534 (48.0%). Of 203 patients with follow-up results, the most recent CD4 was ≤250 cells/μl in 34 (24.5%), and ≤350 cells/μl in 64 (46.0%).ConclusionsCD4 testing in rural clinics is feasible and identifies many patients eligible for ART who would not be identified without CD4 testing. CD4 testing needs to be scaled-up to identify patients eligible for ART. ART services need to be scaled-up concurrently to meet the resulting increased demand

Combinatorial quorum sensing allows bacteria to resolve their social and physical environment

Quorum sensing (QS) is a cell–cell communication system that controls gene expression in many bacterial species, mediated by diffusible signal molecules. Although the intracellular regulatory mechanisms of QS are often well-understood, the functional roles of QS remain controversial. In particular, the use of multiple signals by many bacterial species poses a serious challenge to current functional theories. Here, we address this challenge by showing that bacteria can use multiple QS signals to infer both their social (density) and physical (mass-transfer) environment. Analytical and evolutionary simulation models show that the detection of, and response to, complex social/physical contrasts requires multiple signals with distinct half-lives and combinatorial (nonadditive) responses to signal concentrations. We test these predictions using the opportunistic pathogen Pseudomonas aeruginosa and demonstrate significant differences in signal decay betweeallyn its two primary signal molecules, as well as diverse combinatorial responses to dual-signal inputs. QS is associated with the control of secreted factors, and we show that secretome genes are preferentially controlled by synergistic “AND-gate” responses to multiple signal inputs, ensuring the effective expression of secreted factors in high-density and low mass-transfer environments. Our results support a new functional hypothesis for the use of multiple signals and, more generally, show that bacteria are capable of combinatorial communication

High residual prevalence of vaccine-serotype Streptococcus pneumoniae carriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study

Background: There are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi’s November 2011 introduction of PCV13 using a 3+0 schedule. / Methods: We conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression. / Results: Among PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children. / Conclusion: Compared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required

Non-linear regression models for Approximate Bayesian Computation

Approximate Bayesian inference on the basis of summary statistics is well-suited to complex problems for which the likelihood is either mathematically or computationally intractable. However the methods that use rejection suffer from the curse of dimensionality when the number of summary statistics is increased. Here we propose a machine-learning approach to the estimation of the posterior density by introducing two innovations. The new method fits a nonlinear conditional heteroscedastic regression of the parameter on the summary statistics, and then adaptively improves estimation using importance sampling. The new algorithm is compared to the state-of-the-art approximate Bayesian methods, and achieves considerable reduction of the computational burden in two examples of inference in statistical genetics and in a queueing model.Comment: 4 figures; version 3 minor changes; to appear in Statistics and Computin

The effect of a diet with fructan-rich chicory roots on intestinal helminths and microbiota with special focus on Bifidobacteria and Campylobacter in piglets around weaning

The restrictions on the use of antibiotic and anthelmintic treatments in organic pig farming necessitate alternative non-medical control strategies. Therefore, the antibiotic and parasite-reducing effect of a fructan-rich (prebiotic) diet of dried chicory was investigated in free-ranging piglets. Approximately half of 67 piglets from 9 litters were experimentally infected with Ascaris suum and Trichuris suis in the suckling period (1 to 7 weeks of age) and 58 of the piglets were challenged daily with E. coli O138:F8 for 9 days after weaning to induce weaning diarrhoea. The litters were fed either chicory (30% DM) or a control diet. The effect of chicory on intestinal helminths, intestinal microbiota, especially Bifidobacteria and Campylobacter spp., and E. coli post-weaning diarrhoea was assessed. The weight gain of the piglets was not impaired significantly by chicory. The intestinal A. suum worm burden was reduced by 64% (P=0.034) in the chicory-fed piglets, whereas these same piglets had 63% more T. suis worms (P=0.016). Feeding with chicory elicited no changes among the main bacterial groups in ileum according to terminal restriction fragment length polymorphism (T-RFLP) analysis. However, the terminal-restriction fragment (T-RF) 208 bp, which may belong to Lachnospiraceae, was stimulated by the chicory feed (P=0.03), and T-RF 370 bp that matches Enterobacter belonging to the Enterobacteria was reduced (P=0.004). Additionally, chicory increased the level of Bifidobacteria (P=0.001) and the faecal Campylobacter excretion level was transitorily reduced in chicory-fed piglets at 7 weeks of age (P=0.029). Unfortunately, it was not possible to assess the effect of chicory on post-weaning diarrhoea as it did not develop. In conclusion, feeding piglets chicory around the time of weaning caused complex changes of the microbiota and parasite communities within the intestinal tract, and feeding piglets chicory may therefore serve as an animal-friendly strategy to control pathogens