Long-distance place assimilation with an interacting error pattern in phonological acquisition

Two commonly occurring and independent error patterns in children's early speech are examined to determine how and to what extent they might interact. One error pattern replaces velar consonants with coronals, and the other replaces a coronal with a consonant that agrees in place of articulation with some other consonant elsewhere in the word. A range of interactions is observed within and across children with regard to whether the product of one error pattern can serve as the target of the other. The different interactions motivate different claims about the nature and substance of children's underlying representations, which in some cases may differ from those of the ambient system. An extension to underspecification theory is advanced which allows underlying representations to be radically underspecified and in certain cases also to be specified for a default feature.National Institutes of Health DC00433, RR7031K, DC00076, DC001694 (PI: Gierut)This is an Accepted Manuscript of an article published by Taylor & Francis in Clinical Linguistics & Phonetics on January 1997, available online: http://wwww.tandfonline.com/10.3109/02699209708985198

Performance Evaluation of Cetacean Species Distribution Models Developed Using Generalized Additive Models and Boosted Regression Trees

Species distribution models (SDMs) are important management tools for highly mobile marine species because they provide spatially and temporally explicit information on animal distribution. Two prevalent modeling frameworks used to develop SDMs for marine species are generalized additive models (GAMs) and boosted regression trees (BRTs), but comparative studies have rarely been conducted; most rely on presence-only data; and few have explored how features such as species distribution characteristics affect model performance. Since the majority of marine species BRTs have been used to predict habitat suitability, we first compared BRTs to GAMs that used presence/absence as the response variable. We then compared results from these habitat suitability models to GAMs that predict species density (animals per km2) because density models built with a subset of the data used here have previously received extensive validation. We compared both the explanatory power (i.e., model goodness of fit) and predictive power (i.e., performance on a novel dataset) of the GAMs and BRTs for a taxonomically diverse suite of cetacean species using a robust set of systematic survey data (1991–2014) within the California Current Ecosystem. Both BRTs and GAMs were successful at describing overall distribution patterns throughout the study area for the majority of species considered, but when predicting on novel data, the density GAMs exhibited substantially greater predictive power than both the presence/absence GAMs and BRTs, likely due to both the different response variables and fitting algorithms. Our results provide an improved understanding of some of the strengths and limitations of models developed using these two methods. These results can be used by modelers developing SDMs and resource managers tasked with the spatial management of marine species to determine the best modeling technique for their question of interest

Performance evaluation of cetacean species distribution models developed using generalized additive models and boosted regression trees

Species distribution models (SDMs) are important management tools for highly mobile marine species because they provide spatially and temporally explicit information on animal distribution. Two prevalent modeling frameworks used to develop SDMs for marine species are generalized additive models (GAMs) and boosted regression trees (BRTs), but comparative studies have rarely been conducted; most rely on presence-only data; and few have explored how features such as species distribution characteristics affect model performance. Since the majority of marine species BRTs have been used to predict habitat suitability, we first compared BRTs to GAMs that used presence/absence as the response variable. We then compared results from these habitat suitability models to GAMs that predict species density (animals per km2) because density models built with a subset of the data used here have previously received extensive validation. We compared both the explanatory power (i.e., model goodness of fit) and predictive power (i.e., performance on a novel dataset) of the GAMs and BRTs for a taxonomically diverse suite of cetacean species using a robust set of systematic survey data (1991–2014) within the California Current Ecosystem. Both BRTs and GAMs were successful at describing overall distribution patterns throughout the study area for the majority of species considered, but when predicting on novel data, the density GAMs exhibited substantially greater predictive power than both the presence/absence GAMs and BRTs, likely due to both the different response variables and fitting algorithms. Our results provide an improved understanding of some of the strengths and limitations of models developed using these two methods. These results can be used by modelers developing SDMs and resource managers tasked with the spatial management of marine species to determine the best modeling technique for their question of interest

TRIM16 Acts as an E3 Ubiquitin Ligase and Can Heterodimerize with Other TRIM Family Members

The TRIM family of proteins is distinguished by its tripartite motif (TRIM). Typically, TRIM proteins contain a RING finger domain, one or two B-box domains, a coiled-coil domain and the more variable C-terminal domains. TRIM16 does not have a RING domain but does harbour two B-box domains. Here we showed that TRIM16 homodimerized through its coiled-coil domain and heterodimerized with other TRIM family members; TRIM24, Promyelocytic leukaemia (PML) protein and Midline-1 (MID1). Although, TRIM16 has no classic RING domain, three-dimensional modelling of TRIM16 suggested that its B-box domains adopts RING-like folds leading to the hypothesis that TRIM16 acts as an ubiquitin ligase. Consistent with this hypothesis, we demonstrated that TRIM16, devoid of a classical RING domain had auto-polyubiquitination activity and acted as an E3 ubiquitin ligase in vivo and in vitro assays. Thus via its unique structure, TRIM16 possesses both heterodimerization function with other TRIM proteins and also has E3 ubiquitin ligase activity

SARS-CoV-2 Viral Load in Saliva Rises Gradually and to Moderate Levels in Some Humans

Transmission of SARS-CoV-2 in community settings often occurs before symptom onset, therefore testing strategies that can reliably detect people in the early phase of infection are urgently needed. Early detection of SARS-CoV-2 infection is especially critical to protect vulnerable populations who require frequent interactions with caretakers. Rapid COVID-19 tests have been proposed as an attractive strategy for surveillance, however a limitation of most rapid tests is their low sensitivity. Low-sensitivity tests are comparable to high sensitivity tests in detecting early infections when two assumptions are met: (1) viral load rises quickly (within hours) after infection and (2) viral load reaches and sustains high levels (>10⁵ - 10⁶ RNA copies/mL). However, there are no human data testing these assumptions. In this study, we document a case of presymptomatic household transmission from a healthy college student to his brother and father. Participants prospectively provided twice-daily saliva samples. Samples were analyzed by RT-qPCR and RT-ddPCR and we measured the complete viral load profiles throughout the course of infection of the brother and father. This study provides evidence that in at least some human cases of SARS-CoV-2, viral load rises slowly (over days, not hours) and not to such high levels to be detectable reliably by any low-sensitivity test. Additional viral load profiles from different samples types across a broad demographic must be obtained to describe the early phase of infection and determine which testing strategies will be most effective for identifying SARS-CoV-2 infection before transmission can occur

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Self-management for osteoarthritis of the knee: Does mode of delivery influence outcome?

Background Self-management has become increasingly popular in the management of chronic diseases. There are many different self-management models. Meta analyses of arthritis self-management have concluded that it is difficult to recommend any one program in preference to another due to inconsistencies in the study designs used to evaluate different programs. The Stanford Arthritis Self-Management Program (ASMP), most commonly delivered by trained lay leaders, is a generic program widely used for people with rheumatological disorders. We have developed a more specific program expressly for people with osteoarthritis of the knee (OAKP). It includes information designed to be delivered by health professionals and results in improvements in pain, function and quality of life. Aim: To determine whether, for people with osteoarthritis (OA) of the knee, the OAKP implemented in a primary health care setting can achieve and maintain clinically meaningful improvements in more participants than ASMP delivered in the same environment. Methods/Design The effectiveness of the programs will be compared in a single-blind randomized study. Participants: 146 participants with established OA knee will be recruited. Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded. Interventions: Participants will be randomised into either OAKP or ASMP groups and followed for 6 months. Measurements: Assessments will be immediately before and after the intervention and at 6 months. Primary outcome measures will be WOMAC and SF-36 questionnaires and a VAS for pain. Secondary outcomes will include balance, tested using a timed single leg balance test and a timed step test and self-efficacy. Data will be analysed using repeated measures ANOVA. Discussion With an aging population the health care costs for people with arthritis are ever increasing. Although cost analysis is beyond the scope of this study, it is reasonable to expect that costs will be greater when health professionals deliver self-management programs as opposed to lay leaders. Consequently it is critical to examine the relative effectiveness of the primary care management strategies available for OA

Neuropeptide Y2 Receptor (NPY2R) Expression in Saliva Predicts Feeding Immaturity in the Premature Neonate

Background: The current practice in newborn medicine is to subjectively assess when a premature infant is ready to feed by mouth. When the assessment is inaccurate, the resulting feeding morbidities may be significant, resulting in long-term health consequences and millions of health care dollars annually. We hypothesized that the developmental maturation of hypothalamic regulation of feeding behavior is a predictor of successful oral feeding in the premature infant. To test this hypothesis, we analyzed the gene expression of neuropeptide Y2 receptor (NPY2R), a known hypothalamic regulator of feeding behavior, in neonatal saliva to determine its role as a biomarker in predicting oral feeding success in the neonate. Methodology/Principal Findings: Salivary samples (n = 116), were prospectively collected from 63 preterm and 13 term neonates (post-conceptual age (PCA) 26 4/7 to 41 4/7 weeks) from five predefined feeding stages. Expression of NPY2R in neonatal saliva was determined by multiplex RT-qPCR amplification. Expression results were retrospectively correlated with feeding status at time of sample collection. Statistical analysis revealed that expression of NPY2R had a 95 % positive predictive value for feeding immaturity. NPY2R expression statistically significantly decreased with advancing PCA (Wilcoxon test p value,0.01), and was associated with feeding status (chi square p value = 0.013). Conclusions/Significance: Developmental maturation of hypothalamic regulation of feeding behavior is an essential component of oral feeding success in the newborn. NPY2R expression in neonatal saliva is predictive of an immatur