3) of meeting criteria for this primary outcome. Attainment rates for secondary outcomes (families feeling like partners in care; receives care within a medical home; received needed health care) were significantly lower among CMC than CSHCN. Family income was significantly associated with likelihood of meeting criteria for primary and secondary outcomes; however, the relationships between medical complexity status and our outcomes did not differ by income level.

CMC are less likely than other CSHCN to report receiving care in well-functioning health care systems at all income levels. Further efforts are necessary to better adapt current health care systems to meet the unique needs of CMC.

CMC are less likely than other CSHCN to report receiving care in well-functioning health care systems at all income levels. Further efforts are necessary to better adapt current health care systems to meet the unique needs of CMC.Emu and other ratites are more informative than any other birds in reconstructing the evolution of the ancestral avian or vertebrate karyotype because of their much slower rate of genome evolution. Here, we generated a new chromosome-level genome assembly of a female emu, and estimated the tempo of chromosome evolution across major avian phylogenetic branches, by comparing it to chromosome-level genome assemblies of 11 other bird and one turtle species. We found ratites exhibited the lowest numbers of intra- and inter-chromosomal changes among birds since their divergence with turtles. The small-sized and gene-rich emu microchromosomes have frequent inter-chromosomal contacts that are associated with housekeeping genes, which appears to be driven by clustering their centromeres in the nuclear interior, away from the macrochromosomes in the nuclear periphery. Unlike nonratite birds, only less than one-third of the emu W Chromosome regions have lost homologous recombination and diverged between the sexes. The emu W is demarcated into a highly heterochromatic region (WS0) and another recently evolved region (WS1) with only moderate sequence divergence with the Z Chromosome. WS1 has expanded its inactive chromatin compartment, increased chromatin contacts within the region, and decreased contacts with the nearby regions, possibly influenced by the spreading of heterochromatin from WS0. These patterns suggest that alteration of chromatin conformation comprises an important early step of sex chromosome evolution. Overall, our results provide novel insights into the evolution of avian genome structure and sex chromosomes in three-dimensional space.Antisocial behavior and psychopathic traits are subject to complex patterns of inheritance, gene–environment interactive effects, and powerful environmental influences. Yet genetic factors are important in the etiology of antisocial behavior and psychopathic traits, and identifying youth with an elevated genetic risk may lead to improved interventions and preventive efforts. Additionally, research revealing the importance of gene–environment interactions in the development of antisocial behavior and psychopathic traits should be harnessed to promote more rehabilitative, developmentally appropriate policies to benefit youth in the juvenile justice and social welfare systems.Neural networks in the brain can function reliably despite various sources of errors and noise present at every step of signal transmission. These sources include errors in the presynaptic inputs to the neurons, noise in synaptic transmission, and fluctuations in the neurons’ postsynaptic potentials (PSPs). Collectively they lead to errors in the neurons’ outputs which are, in turn, injected into the network. Does unreliable network activity hinder fundamental functions of the brain, such as learning and memory retrieval? To explore this question, this article examines the effects of errors and noise on the properties of model networks of inhibitory and excitatory neurons involved in associative sequence learning. The associative learning problem is solved analytically and numerically, and it is also shown how memory sequences can be loaded into the network with a biologically more plausible perceptron-type learning rule. Interestingly, the results reveal that errors and noise during learning increase the probability of memory recall. There is a trade-off between the capacity and reliability of stored memories, and, noise during learning is required for optimal retrieval of stored information. What is more, networks loaded with associative memories to capacity display many structural and dynamical features observed in local cortical circuits in mammals. Based on the similarities between the associative and cortical networks, this article predicts that connections originating from more unreliable neurons or neuron classes in the cortex are more likely to be depressed or eliminated during learning, while connections onto noisier neurons or neuron classes have lower probabilities and higher weights.

To determine whether the Alzheimer disease (AD) dementia conversion-related pattern (ADCRP) on [

F]FDG PET can serve as a valid predictor for the development of AD dementia, the individual expression of the ADCRP (subject score) and its prognostic value were examined in patients with mild cognitive impairment (MCI) and biologically defined AD.

A total of 269 patients with available [

F]FDG PET, [

F]AV-45 PET, phosphorylated and total tau in CSF, and neurofilament light chain in plasma were included. Following the AT(N) classification scheme, where AD is defined biologically by in vivo biomarkers of β-amyloid (Aβ) deposition („A”) and pathologic tau („T”), patients were categorized to the A-T-, A+T-, A+T+ (AD), and A-T+ groups.

The mean subject score of the ADCRP was significantly higher in the A+T+ group compared to each of the other group (all

< 0.05) but was similar among the latter (all

> 0.1). Within the A+T+ group, the subject score of ADCRP was a significant predictor of conversion to dementia (hazard ratio, 2.02 per

score increase;

< 0.001), with higher predictive value than of alternative biomarkers of neurodegeneration (total tau and neurofilament light chain). Stratification of A+T+ patients by the subject score of ADCRP yielded well-separated groups of high, medium, and low conversion risks.

The ADCRP is a valuable biomarker of neurodegeneration in patients with MCI and biologically defined AD. It shows great potential for stratifying the risk and estimating the time to conversion to dementia in patients with MCI and underlying AD (A+T+).

This study provides Class I evidence that [

F]FDG PET predicts the development of AD dementia in individuals with MCI and underlying AD as defined by the AT(N) framework.

This study provides Class I evidence that [18F]FDG PET predicts the development of AD dementia in individuals with MCI and underlying AD as defined by the AT(N) framework.For the past 2 decades, high-frequency oscillations (HFOs) have been enthusiastically studied by the epilepsy community. Emerging evidence shows that HFOs harbor great promise to delineate epileptogenic brain areas and possibly predict the likelihood of seizures. Investigations into HFOs in clinical epilepsy have advanced from small retrospective studies relying on visual identification and correlation analysis to larger prospective assessments using automatic detection and prediction strategies. Although most studies have yielded promising results, some have revealed significant obstacles to clinical application of HFOs, thus raising debate about the reliability and practicality of HFOs as clinical biomarkers. In this review, we give an overview of the current state of HFO research and pinpoint the conceptual and methodological issues that have hampered HFO translation. We highlight recent insights gained from long-term data, high-density recordings, and multicenter collaborations and discuss the open questions that need to be addressed in future research.

To determine the clinical phenotypes associated with the amyloid-β PET and dopamine transporter imaging (

I-FP-CIT SPECT) findings in mild cognitive impairment (MCI) with the core clinical features of dementia with Lewy bodies (DLB; MCI-LB).

Patients with MCI who had at least one core clinical feature of DLB (n=34) were grouped into β-amyloid A+ or A- and

I-FP-CIT SPECT D+ or D- groups based on previously established abnormality cut points for A+ with Pittsburgh compound-B PET standardized uptake value ratio (PiB SUVR) ≥1.48 and D+ with putamen z-score with DATQUANT < -0.82 on

I-FP-CIT SPECT. Individual MCI-LB patients fell into one of four groups A+D+, A+D-, A-D+, or A-D-. Log transformed PiB SUVR and putamen z-score were tested for associations with patient characteristics.

The A-D+ biomarker profile was most common (38.2%) followed by A+D+ (26.5%) and A-D- (26.5%). Least common was A+D- biomarker profile (8.8 %). The A+ group was older, had a higher frequency of

ε4 carriers, and a lower MMSE score than the A- group. The D+ group was more likely to have probable rapid eye movement sleep behavior disorder. Lower putamen DATQUANT z-scores and lower PiB SUVRs were independently associated with higher Unified Parkinson Disease Rating Scale (UPDRS)-III scores.

A majority of MCI-LB patients are characterized by low amyloid-β deposition and reduced dopaminergic activity. Amyloid-β PET and

I-FP-CIT SPECT are complementary in characterizing clinical phenotypes of patients with MCI-LB.

A majority of MCI-LB patients are characterized by low amyloid-β deposition and reduced dopaminergic activity. Amyloid-β PET and 123I-FP-CIT SPECT are complementary in characterizing clinical phenotypes of patients with MCI-LB.

To understand the time course of β-amyloid (Aβ) deposition in the brain, which is crucial for planning therapeutic trials of Aβ-lowering therapies in Alzheimer disease (AD).

Two samples of participants from the Alzheimer’s Disease Neuroimaging Initiative were studied with [

F]Florbetapir (FBP) Aβ PET and followed for up to 9 years. Sample A included 475 cognitively normal (CN) older people and those with mild cognitive impairment (MCI) and AD and sample B included 220 CN Aβ- individuals. We examined the trajectory of FBP over time in sample A and the incidence rate of conversion from negative to positive Aβ PET scans in sample B.

The relationship between time and brain Aβ was sigmoidal, taking 6.4 years to transition from amyloid negative to positive and another 13.9 years to the onset of MCI. Aβ deposition rates began to slow only 3.8 years after reaching the positivity threshold. The incidence rate for scan positivity was 38/1,000 person-years, and factors associated with conversion were age, baseline FBP, and being a female

ε4 carrier. Among CN Aβ- individuals, FBP slopes were associated with rates of memory decline and brain tau measured with [

F]Flortaucipir PET 5 years after baseline.

Lowering brain Aβ must be accomplished early in the evolution of AD. Transitions of PET scans from Aβ- to Aβ+ should be predictable, and it is reasonable to expect that lowering rates of Aβ even in early stages could produce clinically significant benefits.

Lowering brain Aβ must be accomplished early in the evolution of AD. Transitions of PET scans from Aβ- to Aβ+ should be predictable, and it is reasonable to expect that lowering rates of Aβ even in early stages could produce clinically significant benefits.