Inelastic Dark Matter at the LHC

We perform a model-independent study of inelastic dark matter at the LHC, concentrating on the parameter space with the mass splitting between the excited and ground states of dark matter above a few hundred MeV, where the direct detection experiments are unlikely to explore. The generic signatures of inelastic dark matter at the LHC are displaced pions together with a monojet plus missing energy, and can be tested at the 7 TeV LHC.Comment: 4 pages, 6 figure

Searches with Mono-Leptons

We explore the implications of the mono-lepton plus missing transverse energy signature at the LHC, and point out its significance on understanding how dark matter interacts with quarks, where the signature arises from dark matter pair production together with a leptonically decaying W boson radiated from the initial state quarks. We derive limits using the existing W' searches at the LHC, and find an interesting interference between the contributions from dark matter couplings to up-type and down-type quarks. Mono-leptons can actually furnish the strongest current bound on dark matter interactions for axial vector (spin-dependent) interactions and iso-spin violating couplings. Should a signal of dark matter production be observed, this process can also help disentangle the dark matter couplings to up- and down-type quarks.Comment: four pages; six figures; the LHC 8 TeV results have been updated; final version in PL

A Framework for Descriptive Epidemiology

In this paper, we propose a framework for thinking through the design and conduct of descriptive epidemiologic studies. A well-defined descriptive question aims to quantify and characterize some feature of the health of a population and must clearly state: 1) the target population, characterized by person and place, and anchored in time; 2) the outcome, event, or health state or characteristic; and 3) the measure of occurrence that will be used to summarize the outcome (e.g., incidence, prevalence, average time to event, etc.). Additionally, 4) any auxiliary variables will be prespecified and their roles as stratification factors (to characterize the outcome distribution) or nuisance variables (to be standardized over) will be stated. We illustrate application of this framework to describe the prevalence of viral suppression on December 31, 2019, among people living with human immunodeficiency virus (HIV) who had been linked to HIV care in the United States. Application of this framework highlights biases that may arise from missing data, especially 1) differences between the target population and the analytical sample; 2) measurement error; 3) competing events, late entries, loss to follow-up, and inappropriate interpretation of the chosen measure of outcome occurrence; and 4) inappropriate adjustment

Flexibly accounting for exposure misclassification with external validation data

Measurement error is common in epidemiology, but few studies use quantitative methods to account for bias due to mismeasurement. One potential barrier is that some intuitive approaches that readily combine with methods to account for other sources of bias, like multiple imputation for measurement error (MIME), rely on internal validation data, which are rarely available. Here, we present a reparameterized imputation approach for measurement error (RIME) that can be used with internal or external validation data. We illustrate the advantages of RIME over a naive approach that ignores measurement error and MIME using a hypothetical example and a series of simulation experiments. In both the example and simulations, we combine MIME and RIME with inverse probability weighting to account for confounding when estimating hazard ratios and counterfactual risk functions. MIME and RIME performed similarly when rich external validation data were available and the prevalence of exposure did not vary between the main study and the validation data. However, RIME outperformed MIME when validation data included only true and mismeasured versions of the exposure or when exposure prevalence differed between the data sources. RIME allows investigators to leverage external validation data to account for measurement error in a wide range of scenarios

Niche variation and the maintenance of variation in body size in a burying beetle

© 2015 The Authors. Ecological Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Online Version of Record published before inclusion in an issue.The final published version is available via DOI: 10.1111/een.122751. In burying beetles (Nicrophorinae) body size is known to provide both a fecundity advantage (in females) and successful resource defence (in males and females). Despite this, considerable variation in body sizes is observed in natural populations. 2. A possible explanation for the maintenance of this variation, even with intra- and interspecific resource competition, is that individuals might assort according to body size on different sized breeding-resources. 3. We tested the prediction that ‘bigger is always better’ in the wild, and in the laboratory, by experimentally manipulating combinations of available breeding-resource size (mouse carcasses) and competitor’s body size in Nicrophorus vespilloides (Herbst 1783). 4. In the field, large female beetles deserted small carcasses, without breeding, more often than they did larger carcasses, but small females used carcasses indiscriminately with respect to size. In the laboratory large beetles reared larger broods (with more offspring) on larger carcasses than small beetles, but on small carcasses small beetles had a reproductive advantage over large ones. Offspring size covaried with carcass size independently of parental body size. 5. Our combined results suggest breeding resource value depends on an individual’s body size, and variation in body size is environmentally induced: maintained by differences in available carcass sizes. This produces a mechanism by which individual specialisation leads to an increase in niche variation via body size in these beetles.This work was supported by a PhD studentship from the Natural Environment Research Council (NE/1528326/1) and a grant from NERC to N.J.R. and A.J.M. (NE/1025468/1)

Has the phasing out of stavudine in accordance with changes in WHO guidelines led to a decrease in single-drug substitutions in first-line antiretroviral therapy for HIV in sub-Saharan Africa?

This version is the Accepted Manuscript and is published in final edited form as: AIDS. 2017 January 02; 31(1): 147–157. doi:10.1097/QAD.0000000000001307OBJECTIVE: We assessed the relationship between phasing out stavudine in first-line antiretroviral therapy (ART) in accordance with WHO 2010 policy and single-drug substitutions (SDS) (substituting the nucleoside reverse transcriptase inhibitor in first-line ART) in sub-Saharan Africa. DESIGN: Prospective cohort analysis (International epidemiological Databases to Evaluate AIDS-Multiregional) including ART-naive, HIV-infected patients aged at least 16 years, initiating ART between January 2005 and December 2012. Before April 2010 (July 2007 in Zambia) national guidelines called for patients to initiate stavudine-based or zidovudine-based regimen, whereas thereafter tenofovir or zidovudine replaced stavudine in first-line ART. METHODS: We evaluated the frequency of stavudine use and SDS by calendar year 2004-2014. Competing risk regression was used to assess the association between nucleoside reverse transcriptase inhibitor use and SDS in the first 24 months on ART. RESULTS: In all, 33 441 (8.9%; 95% confience interval 8.7-8.9%) SDS occurred among 377 656 patients in the first 24 months on ART, close to 40% of which were amongst patients on stavudine. The decrease in SDS corresponded with the phasing out of stavudine. Competing risks regression models showed that patients on tenofovir were 20-95% less likely to require a SDS than patients on stavudine, whereas patients on zidovudine had a 75-85% decrease in the hazards of SDS when compared to stavudine. CONCLUSION: The decline in SDS in the first 24 months on treatment appears to be associated with phasing out stavudine for zidovudine or tenofovir in first-line ART in our study. Further efforts to decrease the cost of tenofovir and zidovudine for use in this setting is warranted to substitute all patients still receiving stavudine

The Critical Importance of Asking Good Questions: The Role of Epidemiology Doctoral Training Programs

Epidemiologic methods have advanced tremendously in the last several decades. As important as they are, even the most sophisticated approaches are unable to provide meaningful answers when the user lacks a clear study question. Yet, instructors have more and more resources on how to conduct studies and analyze data but few resources on how to ask clearly defined study questions that will guide those methods. Training programs have limited time for coursework, and if novel statistical estimation methods become the focus of instruction, programs that go this route may end up underemphasizing the process of asking good study questions, designing robust studies, considering potential biases in the collected data, and appropriately interpreting the results of the analysis. Given the demands for space in curricula, now is an appropriate time to reevaluate what we teach epidemiology doctoral students. We advocate that programs place a renewed focus on asking good study questions and following a comprehensive approach to study design and data analysis in which questions guide the choice of appropriate methods, helping us avoid methods for methods' sake and highlighting when application of a new method can provide the opportunity to answer questions that were intractable with traditional approaches

Introducing non-linear analysis into sustained speech characterization to improve sleep apnea detection

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-25020-0_28Proceedings of 5th International Conference on Nonlinear Speech Processing, NOLISP 2011, Las Palmas de Gran Canaria (Spain)We present a novel approach for detecting severe obstructive sleep apnea (OSA) cases by introducing non-linear analysis into sustained speech characterization. The proposed scheme was designed for providing additional information into our baseline system, built on top of state-of-the-art cepstral domain modeling techniques, aiming to improve accuracy rates. This new information is lightly correlated with our previous MFCC modeling of sustained speech and uncorrelated with the information in our continuous speech modeling scheme. Tests have been performed to evaluate the improvement for our detection task, based on sustained speech as well as combined with a continuous speech classifier, resulting in a 10% relative reduction in classification for the first and a 33% relative reduction for the fused scheme. Results encourage us to consider the existence of non-linear effects on OSA patients’ voices, and to think about tools which could be used to improve short-time analysis.The activities described in this paper were funded by the Spanish Ministry of Science and Innovation as part of the TEC2009-14719-C02-02 (PriorSpeech) project

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases

Background: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). Methods: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. Results: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1–66.2) years and BMI 28.2 (IQR 24.9–32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25–30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97–1.01, p = 0.31) nor blood pressure or GN diagnosis. Conclusion: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression