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When linguistic input contains inconsistent use of grammatical forms, children produce these forms more consistently, a process called ‘regularization.’ Deaf children learning American Sign Language from parents who are non-native users of the language regularize their parents’ inconsistent usages (Singleton & Newport, 2004). In studies of artificial languages containing inconsistently used morphemes (Hudson Kam & Newport, 2005, 2009), children, but not adults, regularized these forms. However, little is known about the precise circumstances in which such regularization occurs. In three experiments we investigate how the type of input variation and the age of learners affects regularization. Overall our results suggest that while adults tend to reproduce the inconsistencies found in their input, young children introduce regularity: they learn varying forms whose occurrence is conditioned and systematic, but they alter inconsistent variation to be more regular. Older children perform more like adults, suggesting that regularization changes with maturation and cognitive capacities.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing neurodevelopmental disorder. While early childhood is a crucial time for early intervention, it is characterized by instability of ADHD diagnosis. Neural correlates of ADHD have potential to improve diagnostic accuracy; however, minimal research has focused on early childhood. Research indicates that disrupted neural connectivity is associated with ADHD in older children. Here, we explore network connectivity as a potential neural correlate of ADHD diagnosis in early childhood. METHOD: We collected EEG data in 52 medication-naïve children with ADHD and in 77 typically developing controls (3–7 years). Data was collected with the EGI 128 HydroCel Sensor Net System, but to optimize the ICA, the data was down sampled to the 10–10 system. Connectivity was measured as the synchronization of the time series of each pair of electrodes. Subsequent analyses utilized graph theoretical methods to further characterize network connectivity. RESULTS: Increased global efficiency, which measures the efficiency of information transfer across the entire brain, was associated with increased inattentive symptom severity. Further, this association was robust to controls for age, IQ, SES, and internalizing psychopathology. CONCLUSIONS: Overall, our findings indicate that increased global efficiency, which suggests a hyper-connected neural network, is associated with elevated ADHD symptom severity. These findings extend previous work reporting disruption of neural network connectivity in older children with ADHD into early childhood.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by hyperactivity/impulsivity and inattentiveness. Efforts toward the development of a biologically based diagnostic test have identified differences in the EEG power spectrum; most consistently reported is an increased ratio of theta to beta power during resting state in those with the disorder, compared with controls. Current approaches calculate theta/beta ratio using fixed frequency bands, but the observed differences may be confounded by other relevant features of the power spectrum, including shifts in peak oscillation frequency and altered slope or offset of the aperiodic 1/ f-like component of the power spectrum. In the present study, we quantify the spectral slope and offset, peak alpha frequency, and band-limited and band-ratio oscillatory power in the resting-state EEG of 3- to 7-yr-old children with and without ADHD. We found that medication-naive children with ADHD had higher alpha power, greater offsets, and steeper slopes compared with typically developing children. Children with ADHD who were treated with stimulants had comparable slopes and offsets to the typically developing group despite a 24-h medication-washout period. We further show that spectral slope correlates with traditional measures of theta/beta ratio, suggesting the utility of slope as a neural marker over and above traditional approaches. Taken with past research demonstrating that spectral slope is associated with executive functioning and excitatory/inhibitory balance, these results suggest that altered slope of the power spectrum may reflect pathology in ADHD. NEW & NOTEWORTHY This article highlights the clinical utility of comprehensively quantifying features of the EEG power spectrum. Using this approach, we identify, for the first time, differences in the aperiodic components of the EEG power spectrum in children with attention-deficit/hyperactivity disorder (ADHD) and provide evidence that spectral slope is a robust indictor of an increase in low- relative to high-frequency power in ADHD.

Background People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. Results We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson’s disease (and none with Alzheimer’s disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. Conclusions We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.

Mild traumatic brain injury (mTBI), or concussion, accounts for 85% of all TBIs. Yet survivors anticipate full cognitive recovery within several months of injury, if not sooner, dependent upon the specific outcome/measure. Recovery is variable and deficits in executive function, e.g., working memory (WM) can persist years post-mTBI. We tested whether cognitive deficits persist in otherwise healthy undergraduates, as a conservative indicator for mTBI survivors at large. We collected WM performance (change detection, n-back tasks) using various stimuli (shapes, locations, letters; aurally presented numbers and letters), and wide-ranging cognitive assessments (e.g., RBANS). We replicated the observation of a general visual WM deficit, with preserved auditory WM. Surprisingly, visual WM deficits were equivalent in participants with a history of mTBI (mean 4.3 years post-injury) and in undergraduates with recent sports-related mTBI (mean 17 days post-injury). In seeking the underlying mechanism of these behavioral deficits, we collected resting state fMRI (rsfMRI) and EEG (rsEEG). RsfMRI revealed significantly reduced connectivity within WM-relevant networks (default mode, central executive, dorsal attention, salience), whereas rsEEG identified no differences (modularity, global efficiency, local efficiency). In summary, otherwise healthy current undergraduates with a history of mTBI present behavioral deficits with evidence of persistent disconnection long after full recovery is expected.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability of around 50%. DNA methylation patterns can serve as biomarkers of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study (EWAS) meta-analysis in 10,462 samples (7,344 ALS patients and 3,118 controls), representing the largest case-control study of DNA methylation for any disease to date. We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We show that DNA-methylation-based proxies for HDL-cholesterol, BMI, white blood cell (WBC) proportions and alcohol intake were independently associated with ALS. Integration of these results with our latest GWAS showed that cholesterol biosynthesis was causally related to ALS. Finally, we found that DNA methylation levels at several DMPs and blood cell proportion estimates derived from DNA methylation data, are associated with survival rate in patients, and could represent indicators of underlying disease processes.

The purpose of this conceptual article is to introduce the construct of change engagement and a model that also consists of change-related organizational resources, change-related job resources and demands, and change-related personal resources. We propose that change engagement is a construct that is theoretically and practically useful for understanding employee reactions to and adoption of organizational change. Drawing from existing models of employee engagement, we add to the change literature by identifying salient change-related organizational resources, job resources, job demands, and personal resources in a previously validated framework that brings together the literature on both engagement and change. By using the proposed change engagement framework, practitioners and researchers will potentially be able to effectively diagnose, manage, and optimize employee change readiness and enthusiasm for ongoing change. Furthermore, the change engagement model (CEM) provides practitioners and researchers with a comprehensive and practically useful model that will be easy to comprehend and communicate. The model can be applied to the planning, implementation, and evaluation of discrete change initiatives, as well as to ongoing change. The model is therefore well-suited to contemporary organizational contexts where change is widely recognized to be a constant.

By employing chip-based capillary zone electrophoresis coupled to high-resolution mass spectrometry, we profiled the plasma metabolome of 134 patients diagnosed with sporadic amyotrophic lateral sclerosis (ALS) (81 males and 53 females) and 118 individuals deemed healthy (49 males and 69 females). The most significant markers (p < 0.01) were creatine, which was 49% elevated, and creatinine and methylhistidine, which were decreased by 20 and 24%, respectively, in ALS patients. The ratio of creatine versus creatinine increased 370 and 200% for male and female ALS patients, respectively. In addition, male ALS patients on an average had 5-13% lower amounts of seven essential amino acids, whereas females did not significantly differ from healthy controls. We developed two models using the metabolite abundances: (1) a classification model for the separation of ALS and healthy samples and (2) a classification model for the prediction of disease progression based on the ALS functional rating score. Utilizing a Monte Carlo cross-validation approach, a linear discriminant analysis model achieved a mean area under the receiver operating characteristic curve (AUC) of 0.85 (0.06) with a mean sensitivity of 80% (9%) and specificity of 78% (10%) for the separation of ALS and controls, respectively. A support vector machine classifier predicted progression categories with an AUC of 0.90 (0.06) with a mean sensitivity of 73% (10%) and a specificity of 86% (5%). Lastly, using a previously reported assay with a stable isotope-labeled (13C315N2) spike-in standard, we were unable to detect the exogenous neurotoxic metabolite, β-methylamino-l-alanine, in the free or protein-bound fraction of any of the 252 plasma samples.

Background: Gene discovery has provided remarkable biological insights into amyotrophic lateral sclerosis (ALS). One challenge for clinical application of genetic testing is critical evaluation of the significance of reported variants. Methods: We use whole exome sequencing (WES) to develop a clinically relevant approach to identify a subset of ALS patients harboring likely pathogenic mutations. In parallel, we assess if DNA methylation can be used to screen for pathogenicity of novel variants since a methylation signature has been shown to associate with the pathogenic C9orf72 expansion, but has not been explored for other ALS mutations. Australian patients identified with ALS-relevant variants were cross-checked with population databases and case reports to critically assess whether they were “likely causal,” “uncertain significance,” or “unlikely causal.”. Results: Published ALS variants were identified in >10% of patients; however, in only 3% of patients (4/120) could these be confidently considered pathogenic (in SOD1 and TARDBP). We found no evidence for a differential DNA methylation signature in these mutation carriers. Conclusions: The use of WES in a typical ALS clinic demonstrates a critical approach to variant assessment with the capability to combine cohorts to enhance the largely unknown genetic basis of ALS Refereed/Peer-reviewed

Previous studies have shown that adults are able to remember more than 1,000 images with great detail. However, little is known about the development of this visual capacity, nor its presence early in life. This study tests the level of detail of young children’s memory for a large number of items, adapting the method of Brady, Konkle, Alvarez, and Oliva ( 2008 ). Four- and six-year-old children were shown more than 100 images of everyday objects. They were then tested for recognition of familiar items in a binary decision task. The identity of the foil test item was manipulated in three conditions (Category, Exemplar, and State). Children demonstrated high accuracy across all conditions, remembering not only the basic-level category (Category), but also unique details (Exemplar), and information about position and arrangement of parts (State). These findings demonstrate that children spontaneously encode a high degree of visual detail. Early in life, visual memory exhibits high fidelity and extends over a large set of items.

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10−8), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10−3). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS., Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Leprosy reactions are an important contributor to nerve damage in patients with leprosy. Thus, it is critical to timely diagnose and effectively control them to prevent further nerve damage. Diagnosis of leprosy reactions is clinical because there are no laboratory tests or markers available

Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD. We sincerely thank all patients who contributed to this study and all staff who facilitated their involvement. Funding for this study was provided by the Health Research Board (HRB Ireland; HRA/2009/45) and Science Foundation Ireland (SFI; 08/IN.1/B1916). Next-generation sequencing was performed in TrinSeq (Trinity Genome Sequencing Laboratory; http://www.medicine.tcd.ie/sequencing), a core facility funded by SFI under Grant No. [07/RFP/GEN/F327/EC07] to Dr Morris. Ms Furlong’s PhD studentship is funded by the HRB 4-Year PhD Programme in Molecular Medicine at TCD. We acknowledge use of the Trinity Biobank control sample and support from the Trinity Centre for High Performance Computing. This work was supported by grant funding from the Health Research Board (Ireland). peer-reviewed

Summary • The purposes of this study were twofold. The first was to determine the rationale behind the adoption of a self-care approach to nursing. The second, to determine how a self-care philosophy is applied in practice. • The study was carried out from a phenomenological perspective, as it facilitated an understanding of nursing practice from the practitioners' perspective. • The adoption of a self-care philosophy and approach to caring, appears to have evolved through patients need. This finding has implications for all practitioners.