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Regression trees for longitudinal data with baseline covariates
No full textLongitudinal changes in a population of interest are often heterogeneous and may be influenced by a combination of baseline factors. In such cases, traditional linear mixed effects models (Laird and Ware, 1982) assuming common parametric form for the mean structure may not be applicable. We show that the regression tree methodology for longitudinal data can identify and characterize longitudinally homogeneous subgroups. Most of the currently available regression tree construction methods are either limited to a repeated measures scenario or combine the heterogeneity among subgroups with the random inter-subject variability. We propose a longitudinal classification and regression tree (LongCART) algorithm under conditional inference framework (Hothorn, Hornik and Zeileis, 2006) that overcomes these limitations utilizing a two-step approach. The LongCART algorithm first selects the partitioning variable via a parameter instability test and then finds the optimal split for the selected partitioning variable. Thus, at each node, the decision of further splitting is type-I error controlled and thus it guards against variable selection bias, over-fitting and spurious splitting. We have obtained the asymptotic results for the proposed instability test and examined its finite sample behavior through simulation studies. Comparative performance of LongCART algorithm were evaluated empirically via simulation studies. Finally, we applied LongCART to study the longitudinal changes in choline levels among HIV-positive patients
Association Between the Number of Certified Buprenorphine Prescribers and the Quantity of Buprenorphine Prescriptions: Evidence from 2015 to 2017
No full textIncreasing access to buprenorphine treatment for opioid use disorder is a key strategy for reducing overdoses.1 However, treatment capacity is limited because buprenorphine can only be prescribed by certified providers. To expand capacity, recent federal initiatives have increased the physician patient cap (which previously rose from 30 to 100 patients) to 275 patients, and have allowed nurse practitioners (NPs) and physician assistants (PAs) to obtain waivers.2 Previous research has shown that expanding buprenorphine prescribers for Medicaid populations leads to more buprenorphine prescriptions3; however, it is unclear if this relationship holds across all payer groups
When facial expressions do and do not signal minds: The role of face inversion, expression dynamism, and emotion type.
No full text[Correction Notice: An Erratum for this article was reported in Vol 19(7) of Emotion (see record 2019-57835-002). In the article. the supplemental materials link (http://dx.doi.org/10.1037/emo0000475.supp) was missing from the first page of the article. The supplemental materials are now available online, and the online version of this article has been corrected.] Recent research has linked facial expressions to mind perception. Specifically, Bowling and Banissy (2017) found that ambiguous doll-human morphs were judged as more likely to have a mind when smiling. Herein, we investigate 3 key potential boundary conditions of this “expression-to-mind” effect. First, we demonstrate that face inversion impairs the ability of happy expressions to signal mindful states in static faces; however, inversion does not disrupt this effect for dynamic displays of emotion. Finally, we demonstrate that not all emotions have equivalent effects. Whereas happy faces generate more mind ascription compared to neutral faces, we find that expressions of disgust actually generate less mind ascription than those of happiness. (PsycINFO Database Record (c) 2019 APA, all rights reserved
Engineering a Decoy Substrate in Soybean to Enable Recognition of the Soybean Mosaic Virus NIa Protease.
No full textIn Arabidopsis, recognition of the AvrPphB effector protease from Pseudomonas syringae is mediated by the disease resistance (R) protein RPS5, which is activated by AvrPphB-induced cleavage of the Arabidopsis protein kinase PBS1. The recognition specificity of RPS5 can be altered by substituting the AvrPphB cleavage site within PBS1 with cleavage sequences for other proteases, including proteases from viruses. AvrPphB also activates defense responses in soybean (Glycine max), suggesting that soybean may contain an R protein analogous to RPS5. It was unknown, however, whether this response is mediated by cleavage of a soybean PBS1-like protein. Here, we show that soybean contains three PBS1 orthologs and that their products are cleaved by AvrPphB. Further, transient expression of soybean PBS1 derivatives containing a five-alanine insertion at their AvrPphB cleavage sites activated cell death in soybean protoplasts, demonstrating that soybean likely contains an AvrPphB-specific resistance protein that is activated by a conformational change in soybean PBS1 proteins. Significantly, we show that a soybean PBS1 decoy protein modified to contain a cleavage site for the soybean mosaic virus (SMV) NIa protease triggers cell death in soybean protoplasts when cleaved by this protease, indicating that the PBS1 decoy approach will work in soybean, using endogenous PBS1 genes. Lastly, we show that activation of the AvrPphB-dependent cell death response effectively inhibits systemic spread of SMV in soybean. These data also indicate that decoy engineering may be feasible in other crop plant species that recognize AvrPphB protease activity
Convergent Evolution of Effector Protease Recognition by Arabidopsis and Barley.
No full textThe Pseudomonas syringae cysteine protease AvrPphB activates the Arabidopsis resistance protein RPS5 by cleaving a second host protein, PBS1. AvrPphB induces defense responses in other plant species, but the genes and mechanisms mediating AvrPphB recognition in those species have not been defined. Here, we show that AvrPphB induces defense responses in diverse barley cultivars. We also show that barley contains two PBS1 orthologs, that their products are cleaved by AvrPphB, and that the barley AvrPphB response maps to a single locus containing a nucleotide-binding leucine-rich repeat (NLR) gene, which we termed AvrPphB Response 1 (Pbr1). Transient coexpression of PBR1 with wild-type AvrPphB but not with a protease inactive mutant triggered defense responses, indicating that PBR1 detects AvrPphB protease activity. Additionally, PBR1 coimmunoprecipitated with barley and Nicotiana benthamiana PBS1 proteins, suggesting mechanistic similarity to detection by RPS5. Lastly, we determined that wheat cultivars also recognize AvrPphB protease activity and contain two putative Pbr1 orthologs. Phylogenetic analyses showed, however, that Pbr1 is not orthologous to RPS5. Our results indicate that the ability to recognize AvrPphB evolved convergently and imply that selection to guard PBS1-like proteins occurs across species. Also, these results suggest that PBS1-based decoys may be used to engineer protease effector recognition–based resistance in barley and wheat
Evolution of Intermediates during Capsid Assembly of Hepatitis B Virus with Phenylpropenamide-Based Antivirals
No full textSelf-assembly of virus capsids is a potential target for antivirals due to its importance in the virus lifecycle. Here, we investigate the effect of phenylpropenamide derivatives B-21 and AT-130 on the assembly of hepatitis B virus (HBV) core protein. Phenylpropenamides are widely believed to yield assembly of spherical particles resembling native, empty HBV capsids. Because the details of assembly can be overlooked with ensemble measurements, we performed resistive-pulse sensing on nanofluidic devices with four pores in series to characterize the size distributions of the products in real time. With its single particle sensitivity and compatibility with typical assembly buffers, resistive-pulse sensing is well-suited for analyzing virus assembly in vitro. We observed that assembly with B-21 and AT-130 produced a large fraction of partially complete virus particles that may be on-path, off-path, or trapped. For both B-21 and AT-130, capsid assembly was more sensitive to disruption under conditions where the interprotein association energy was low at lower salt concentrations. Dilution of the reaction solutions led to the rearrangement of the incomplete particles and demonstrated that these large intermediates may be on-path, but are labile, and exist in a frustrated dynamic equilibrium. During capsid assembly, phenylpropenamide molecules modestly increase the association energy of dimers, prevent intermediates from dissociating, and lead to kinetic trapping where the formation of too many capsids has been initiated, which results in both empty and incomplete particles
New Perspectives on the Aging Lexicon
No full textPast work suggests that normal and pathological aging are associated with changes in lexical and semantic cognition. We review recent evidence on how life span changes in size and structure of the mental lexicon impact lexical and semantic cognition. We argue that models of the aging mental lexicon must integrate both ecological and psychological factors and propose a research framework that distinguishes environmental exposure from cognitive mechanisms of learning, representation, and retrieval of information. Our framework emphasizes the need for interdisciplinary collaboration between linguistics, psychology, and neuroscience to generate insights into the ecological and computational basis of the aging mental lexicon. The field of cognitive aging has seen considerable advances in describing the linguistic and semantic changes that happen during the adult life span to uncover the structure of the mental lexicon (i.e., the mental repository of lexical and conceptual representations). Nevertheless, there is still debate concerning the sources of these changes, including the role of environmental exposure and several cognitive mechanisms associated with learning, representation, and retrieval of information. We review the current status of research in this field and outline a framework that promises to assess the contribution of both ecological and psychological aspects to the aging lexicon
NFL blood levels are moderated by subconcussive impacts in a cohort of college football players
No full textIntroduction: Repetitive subconcussive head impacts in contact/collision sports such as in US football are believed to contribute to long-term brain changes and chronic symptoms. However, the lack of tools to measure the effects of repeated subconcussion limits our understanding of potential contributions to neuropathological alterations including cellular damage. Methods: We examined subconcussive head impacts using an accelerometer-embedded mouthguard on changes in blood levels of neurofilament light (NFL) chain in 18 Division I college football players. Plasma levels of NFL and clinical symptoms were assessed at pre-post practices. The frequency and linear and rotational head accelerations recorded via the mouthguard were examined in relation to NFL plasma changes. Results: The frequency and magnitude of head impacts associated with increased NFL levels. The greater numbers of hits and head accelerations associated with greater pre- to post-practice NFL level increases (p < 0.05). Greater pre- to post-practice increases in NFL also associated with greater pre- to post-practice increases in S100β (p < 0.001), but not with total tau. Years of football experience and concussion history did not associate with changes in NFL. Conclusion: Acute changes in NFL may be a clinically useful peripheral marker in tracking acute brain damage in collegiate football players, and other contact sports
Visual Search Performance Does Not Relate to Autistic Traits in the General Population
No full textAutism spectrum disorder (ASD) is commonly conceived as the extreme end of a continuum. Research suggests that autistic individuals outperform typically developing controls in visual search. Thus, enhanced visual search may represent an adaptive trait associated with ASD. Here, using a large general population sample (N = 608, aged 9–14 years), we tested if higher levels of autistic traits are associated with enhanced visual search. Visual search was evaluated using both manual responses and eye movements, and autistic traits were measured using the Social Responsiveness Scale. Contrary to our hypothesis, no significant relation between autistic traits and visual search were observed. The theoretical implications of these results are discussed
