Bayesian Semiparametric Multivariate Density Deconvolution

© 2018 American Statistical Association. We consider the problem of multivariate density deconvolution when interest lies in estimating the distribution of a vector valued random variable X but precise measurements on X are not available, observations being contaminated by measurement errors U. The existing sparse literature on the problem assumes the density of the measurement errors to be completely known. We propose robust Bayesian semiparametric multivariate deconvolution approaches when the measurement error density of U is not known but replicated proxies are available for at least some individuals. Additionally, we allow the variability of U to depend on the associated unobserved values of X through unknown relationships, which also automatically includes the case of multivariate multiplicative measurement errors. Basic properties of finite mixture models, multivariate normal kernels, and exchangeable priors are exploited in novel ways to meet modeling and computational challenges. Theoretical results showing the flexibility of the proposed methods in capturing a wide variety of data-generating processes are provided. We illustrate the efficiency of the proposed methods in recovering the density of X through simulation experiments. The methodology is applied to estimate the joint consumption pattern of different dietary components from contaminated 24 h recalls. Supplementary materials for this article are available online

Effectiveness of a brief community outreach tobacco cessation intervention in India: a cluster-randomised controlled trial (the BABEX Trial)

BACKGROUND: Tobacco use kills half a million people every month, most in low-middle income countries (LMICs). There is an urgent need to identify potentially low-cost, scalable tobacco cessation interventions for these countries. OBJECTIVE: To evaluate a brief community outreach intervention delivered by health workers to promote tobacco cessation in India. DESIGN: Cluster-randomised controlled trial. SETTING: 32 low-income administrative blocks in Delhi, half government authorised ('resettlement colony') and half unauthorised ('J.J. cluster') communities. PARTICIPANTS: 1213 adult tobacco users. INTERVENTIONS: Administrative blocks were computer randomised in a 1:1 ratio, to the intervention (16 clusters; n=611) or control treatment (16 clusters; n=602), delivered and assessed at individual level between 07/2012 and 11/2013. The intervention was single session quit advice (15 min) plus a single training session in yogic breathing exercises; the control condition comprised very brief quit advice (1 min) alone. Both were delivered via outreach, with contact made though household visits. MEASUREMENTS: The primary outcome was 6-month sustained abstinence from all tobacco, assessed 7 months post intervention delivery, biochemically verified with salivary cotinine. RESULTS: The smoking cessation rate was higher in the intervention group (2.6% (16/611)) than in the control group (0.5% (3/602)) (relative risk=5.32, 95% CI 1.43 to 19.74, p=0.013). There was no interaction with type of tobacco use (smoked vs smokeless). Results did not change materially in adjusted analyses, controlling for participant characteristics. CONCLUSIONS: A single session community outreach intervention can increase tobacco cessation in LMIC. The effect size, while small, could impact public health if scaled up with high coverage. TRIAL REGISTRATION NUMBER: ISRCTCN23362894

The Social Gradient in Tobacco Use Does Not Generalize to Low-Income Urban Communities in India: Findings From a Census Survey.

INTRODUCTION: The existence of a social gradient in tobacco use has been clearly established in a number of countries with people with lower socioeconomic status being more likely to use tobacco. It is not clear how far this gradient is evident within severely deprived communities. This study assessed the association between occupation as a marker of socioeconomic status and use of smoked and smokeless tobacco within "slum" areas of Delhi, India. METHODS: A census survey of 11 888 households, comprising 30 655 adults from 28 low-income communities (14 government-authorized and 14 unauthorized settlements called "Jhuggi-Jhopri/JJ" clusters) was conducted in 2012. The survey assessed age, sex, household size, occupational group, and current tobacco use. Independent associations with tobacco use were conducted using complex samples regression analysis, stratified by gender. RESULTS: A quarter of participants (24.3%, 95% confidence interval [CI] 21.5-27.5) used any tobacco. Slightly more people used smoked (14.6%, 95% CI 12.9-16.3) than smokeless (12.6%, 95% CI 10.7-14.8) tobacco, with a small minority being dual users (2.7%, 95% CI 2.1-3.5). Prevalence of any tobacco use was highest in unskilled (45.13%, 95% CI 42.4-47.9) and skilled (46.2%, 95% CI 41.1-51.4) manual occupations and lower in nonmanual (30.3%, 95% CI 26.2-34.7) occupations and those who were unemployed (29.0%, 95% CI 25.3-33.0). This was confirmed in adjusted analysis in men but associations were more complex in women. CONCLUSIONS: Use of smoked and smokeless tobacco in low-income urban communities in India has a complex association with occupational status with both nonmanual occupation and unemployment being associated with lower prevalence of smoked and smokeless tobacco in men. IMPLICATIONS: Tobacco use in high-income countries shows a strong inverse relationship with social grade, income, and deprivation such that use is much more common among those who can least afford it. This study is the first to look at this social gradient in the context of low-income communities in India, finding that both unemployment and nonmanual occupation were associated with lower rates of tobacco use in men. The data present a challenge to existing explanations of the social gradient, requiring further consideration of the conditions under which affordability may work to reduce health inequalities arising from tobacco use

The acute effects of yogic breathing exercises on craving and withdrawal symptoms in abstaining smokers

Rationale Breathing exercises have been proposed as a way of combating cigarette cravings, potentially presenting a low-cost, easily scalable smoking cessation aid. Objective The aim of this study is to evaluate the acute impact of breathing exercises based on yogic pranayama on cravings in abstaining smokers. Methods Participants visited the laboratory on two occasions 24 h apart and were asked to abstain from smoking12 h prior to the first visit until the end of the second visit. Smokers (N = 96) were randomly allocated to a yogic breathing exercise (YBG) or video control (VCG) group. The former was instructed on breathing exercises, practised these for 10 min and asked to use these when experiencing cravings until the next visit. The latter was shown a breathing exercise video for 10 min and asked to concentrate on their breathing. Strength of urges to smoke, other craving measures and mood and physical symptoms associated with cigarette withdrawal were assessed at the beginning and end of the first visit, and again at the second visit. Results At immediate follow-up, in the laboratory, all craving measures were reduced in YBG compared with VCG (strength of urges: F(1, 96) = 16.1, p < 0.001; cigarette craving: F(1, 96) = 11.3, p = 0.001; desire to smoke: F(1, 96) = 6.6, p = 0.012). There was no effect on mood or physical symptoms. Adherence to the breathing exercise regimen in the following 24 h was low, and at 24 h follow-up, there was no evidence of reduced cravings in YBG compared with VCG. Conclusions Simple yogic-style breathing exercises can reduce cigarette craving acutely in the laboratory. Further research is needed to determine how far this translates into field settings

Neotropical Bats: Estimating Species Diversity with DNA Barcodes

DNA barcoding using the cytochrome c oxidase subunit 1 gene (COI) is frequently employed as an efficient method of species identification in animal life and may also be used to estimate species richness, particularly in understudied faunas. Despite numerous past demonstrations of the efficiency of this technique, few studies have attempted to employ DNA barcoding methodologies on a large geographic scale, particularly within tropical regions. In this study we survey current and potential species diversity using DNA barcodes with a collection of more than 9000 individuals from 163 species of Neotropical bats (order Chiroptera). This represents one of the largest surveys to employ this strategy on any animal group and is certainly the largest to date for land vertebrates. Our analysis documents the utility of this tool over great geographic distances and across extraordinarily diverse habitats. Among the 163 included species 98.8% possessed distinct sets of COI haplotypes making them easily recognizable at this locus. We detected only a single case of shared haplotypes. Intraspecific diversity in the region was high among currently recognized species (mean of 1.38%, range 0–11.79%) with respect to birds, though comparable to other bat assemblages. In 44 of 163 cases, well-supported, distinct intraspecific lineages were identified which may suggest the presence of cryptic species though mean and maximum intraspecific divergence were not good predictors of their presence. In all cases, intraspecific lineages require additional investigation using complementary molecular techniques and additional characters such as morphology and acoustic data. Our analysis provides strong support for the continued assembly of DNA barcoding libraries and ongoing taxonomic investigation of bats

Defining the Boundaries of Development wih Plasticity

International audienceThe concept of plasticity has always been present in the history of developmental biology, both within the theory of epigenesis and within morphogenesis studies. However this tradition relies also upon a genetic conception of plasticity. Founded upon the concepts of "phenotypic plasticity" and "reaction norm," this genetic conception focuses on the array of possible phenotypic change in relation to diversified environments. Another concept of plasticity can be found in recent publications by some developmental biologists (Gilbert, West-Eberhard). I argue that these authors adopt a "broad conception of plasticity" that is closely related to a notion of development as something that is ongoing throughout an organism's lifecycle, and has no clear-cut boundaries. However, I suggest that given a narrow conception of plasticity, one can define temporal boundaries for development that are linked to specific features of the morphological process, which are different from behavioral and physiological processes

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

Fluorescence Polarization and Fluctuation Analysis Monitors Subunit Proximity, Stoichiometry, and Protein Complex Hydrodynamics

Förster resonance energy transfer (FRET) microscopy is frequently used to study protein interactions and conformational changes in living cells. The utility of FRET is limited by false positive and negative signals. To overcome these limitations we have developed Fluorescence Polarization and Fluctuation Analysis (FPFA), a hybrid single-molecule based method combining time-resolved fluorescence anisotropy (homo-FRET) and fluorescence correlation spectroscopy. Using FPFA, homo-FRET (a 1–10 nm proximity gauge), brightness (a measure of the number of fluorescent subunits in a complex), and correlation time (an attribute sensitive to the mass and shape of a protein complex) can be simultaneously measured. These measurements together rigorously constrain the interpretation of FRET signals. Venus based control-constructs were used to validate FPFA. The utility of FPFA was demonstrated by measuring in living cells the number of subunits in the α-isoform of Venus-tagged calcium-calmodulin dependent protein kinase-II (CaMKIIα) holoenzyme. Brightness analysis revealed that the holoenzyme has, on average, 11.9±1.2 subunit, but values ranged from 10–14 in individual cells. Homo-FRET analysis simultaneously detected that catalytic domains were arranged as dimers in the dodecameric holoenzyme, and this paired organization was confirmed by quantitative hetero-FRET analysis. In freshly prepared cell homogenates FPFA detected only 10.2±1.3 subunits in the holoenzyme with values ranging from 9–12. Despite the reduction in subunit number, catalytic domains were still arranged as pairs in homogenates. Thus, FPFA suggests that while the absolute number of subunits in an auto-inhibited holoenzyme might vary from cell to cell, the organization of catalytic domains into pairs is preserved

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration