Semiparametric Multivariate Accelerated Failure Time Model with Generalized Estimating Equations

The semiparametric accelerated failure time model is not as widely used as the Cox relative risk model mainly due to computational difficulties. Recent developments in least squares estimation and induced smoothing estimating equations provide promising tools to make the accelerate failure time models more attractive in practice. For semiparametric multivariate accelerated failure time models, we propose a generalized estimating equation approach to account for the multivariate dependence through working correlation structures. The marginal error distributions can be either identical as in sequential event settings or different as in parallel event settings. Some regression coefficients can be shared across margins as needed. The initial estimator is a rank-based estimator with Gehan's weight, but obtained from an induced smoothing approach with computation ease. The resulting estimator is consistent and asymptotically normal, with a variance estimated through a multiplier resampling method. In a simulation study, our estimator was up to three times as efficient as the initial estimator, especially with stronger multivariate dependence and heavier censoring percentage. Two real examples demonstrate the utility of the proposed method

Can agricultural cultivation methods influence the healthfulness of crops for foods

The aim of the current study was to investigate if there are any health effects of long-term consumption of organically grown crops using a rat model. Crops were retrieved over two years from along-term field trial at three different locations in Denmark, using three different cultivation systems(OA, organic based on livestock manure; OB, organic based on green manure; and C, conventional with mineral fertilizers and pesticides)with two field replicates. The cultivation system had an impact on the nutritional quality, affecting γ-tocopherol, some amino acids, and fatty acid composition. Additionally, the nutritional quality was affected by harvest year and location. However, harvest year and location rather than cultivation system affected the measured health biomarkers. In conclusion, the differences in dietary treatments composed of ingredients from different cultivation systems did not lead to significant differences in the measured health biomarkers, except for a significant difference in plasma IgGl evels

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

A temporal dimension to the influence of pollen rewards on bee behaviour and fecundity in Aloe tenuior

The net effect of pollen production on fecundity in plants can range from negative – when self-pollen interferes with fecundity due to incompatibility mechanisms, to positive – when pollen availability is associated with increased pollinator visitation and fecundity due to its utilization as a reward. We investigated the responses of bees to pollen and nectar rewards, and the effects of these rewards on pollen deposition and fecundity in the hermaphroditic succulent shrub Aloe tenuior. Self-pollinated plants failed to set fruit, but their ovules were regularly penetrated by self-pollen tubes, which uniformly failed to develop into seeds as expected from ovarian self-incompatibility (or strong early inbreeding depression). Bees consistently foraged for pollen during the morning and early afternoon, but switched to nectar in the late afternoon. As a consequence of this differential foraging, we were able to test the relative contribution to fecundity of pollen- versus nectar-collecting flower visitors. We exposed emasculated and intact flowers in either the morning or late afternoon to foraging bees and showed that emasculation reduced pollen deposition by insects in the morning, but had little effect in the afternoon. Despite the potential for self-pollination to result in ovule discounting due to late-acting self-sterility, fecundity was severely reduced in artificially emasculated plants. Although there were temporal fluctuations in reward preference, most bee visits were for pollen rewards. Therefore the benefit of providing pollen that is accessible to bee foragers outweighs any potential costs to fitness in terms of gender interference in this species

The factors driving evolved herbicide resistance at a national scale

Repeated use of xenobiotic chemicals has selected for the rapid evolution of resistance threatening health and food security at a global scale. Strategies for preventing the evolution of resistance include cycling and mixtures of chemicals and diversification of management. We currently lack large-scale studies that evaluate the efficacy of these different strategies for minimizing the evolution of resistance. Here we use a national scale dataset of occurrence of the weed Alopecurus myosuroides (Blackgrass) in the UK to address this. Weed densities are correlated with assays of evolved resistance, supporting the hypothesis that resistance is driving weed abundance at a national scale. Resistance was correlated with the frequency of historical herbicide applications suggesting that evolution of resistance is primarily driven by intensity of exposure to herbicides, but was unrelated directly to other cultural techniques. We find that populations resistant to one herbicide are likely to show resistance to multiple herbicide classes. Finally, we show that the economic costs of evolved resistance are considerable: loss of control through resistance can double the economic costs of weeds. This research highlights the importance of managing threats to food production and healthcare systems using an evolutionarily informed approach in a proactive not reactive manner

Suicide attempts and related factors in patients admitted to a general hospital: a ten-year cross-sectional study (1997-2007)

[Abstract] Background: Suicide and suicide attempts represent a severe problem for public health services. The aim of this study is to determine the socio-demographic and psychopathological variables associated with suicide attempts in the population admitted to a General Hospital. Methods: An observational-descriptive study of patients admitted to the A Coruña University Hospital (Spain) during the period 1997-2007, assessed by the Consultation and Liaison Psychiatric Unit. We include n = 5,234 admissions from 4,509 patients. Among these admissions, n = 361 (6.9%) were subsequent to a suicide attempt. Admissions arising from a suicide attempt were compared with admissions occurring due to other reasons.Multivariate generalised estimating equation logistic regression models were used to examine factors associated with suicide attempts. Results: Adjusting by age, gender, educational level, cohabitation status, being employed or unemployed, the psychiatric diagnosis at the time of the interview and the information on previous suicide attempts, we found that the variables associated with the risk of a suicide attempt were: age, psychiatric diagnosis and previous suicide attempts. The risk of suicide attempts decreases with age (OR = 0.969). Psychiatric diagnosis was associated with a higher risk of suicide attempts, with the highest risk being found for Mood or Affective Disorders (OR = 7.49), followed by Personality Disorders (OR = 7.31), and Schizophrenia and Other Psychotic Disorders (OR = 5.03).The strongest single predictive factor for suicide attempts was a prior history of attempts (OR = 23.63). Conclusions: Age, psychopathological diagnosis and previous suicide attempts are determinants of suicide attempts

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target

Does working memory training have to be adaptive?

This study tested the common assumption that, to be most effective, working memory (WM) training should be adaptive (i.e., task difficulty is adjusted to individual performance). Indirect evidence for this assumption stems from studies comparing adaptive training to a condition in which tasks are practiced on the easiest level of difficulty only [cf. Klingberg (Trends Cogn Sci 14:317-324, 2010)], thereby, however, confounding adaptivity and exposure to varying task difficulty. For a more direct test of this hypothesis, we randomly assigned 130 young adults to one of the three WM training procedures (adaptive, randomized, or self-selected change in training task difficulty) or to an active control group. Despite large performance increases in the trained WM tasks, we observed neither transfer to untrained structurally dissimilar WM tasks nor far transfer to reasoning. Surprisingly, neither training nor transfer effects were modulated by training procedure, indicating that exposure to varying levels of task difficulty is sufficient for inducing training gains

The integration of occlusion and disparity information for judging depth in autism spectrum disorder

In autism spectrum disorder (ASD), atypical integration of visual depth cues may be due to flattened perceptual priors or selective fusion. The current study attempts to disentangle these explanations by psychophysically assessing within-modality integration of ordinal (occlusion) and metric (disparity) depth cues while accounting for sensitivity to stereoscopic information. Participants included 22 individuals with ASD and 23 typically developing matched controls. Although adults with ASD were found to have significantly poorer stereoacuity, they were still able to automatically integrate conflicting depth cues, lending support to the idea that priors are intact in ASD. However, dissimilarities in response speed variability between the ASD and TD groups suggests that there may be differences in the perceptual decision-making aspect of the task

A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci

Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 × 10-8, including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 × 10 -21); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 × 10 -12); 5p13.1 near PTGER4 (rs7720838, P = 8.2 × 10 -11); 2q33.1 in PLCL1 (rs10497813, P = 6.1 × 10-10), 3q28 in LPP (rs9860547, P = 1.2 × 10-9); 20q13.2 in NFATC2 (rs6021270, P = 6.9 × 10-9), 4q27 in ADAD1 (rs17388568, P = 3.9 × 10-8); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 × 10-8). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 × 10-12), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease