Technical Reviewing for the Family First Prevention Services Act: Strategies and Recommendations

The Family First Prevention Services Act (FFPSA) has compelled states to expand their priorities to implement evidence-based practices (EBPs) as a means to prevent foster care placement. While the states may opt to include EBPs already approved by the Administration for Children and Families (ACF), some state leaders are opting to commission an independent technical review for the EBP they would prefer to implement as part of their FFPSA plan. While the goal is for ACF to approve their plan and issue a temporary license, little guidance is provided on how to conduct technical reviews. Relying upon the expectations that ACF has outlined for each state, we illustrate the process for conducting reviews of SafeCare in Iowa and Utah and of Family-Centered Treatment in Arkansas. Despite FFPSA and ACF guidance, rendering an evidence rating was difficult given the variability in how some studies measured baseline equivalence, lack of robust testing methods, and conflicting findings across studies. We conclude with recommendations on addressing these challenges and strategies for conducting high-quality technical reviews. The review process offers an opportunity to synthesize a large body of research to inform child welfare practice

Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR=0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR=0.022, opposite direction of effect). Conclusions: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP

Genes Integral to the Reproductive Function of Male Reproductive Tissues Drive Heterogeneity in Evolutionary Rates in Japanese Quail

Early comparative genomics studies originally uncovered a nonintuitive pattern; genes involved in reproduction appeared to evolve more rapidly than other classes of genes. Currently, the emerging consensus is that genes encoding reproductive proteins evolve under variable selective pressures, producing more heterogeneous divergence patterns than previously appreciated. Here, we investigate a facet of that heterogeneity and explore the factors that drive male reproductive tissue-based heterogeneity in evolutionary rates. In Japanese quail (Coturnix japonica), genes with enriched expression in the testes evolve much more rapidly than those enriched in the foam gland (FG), a novel gland that secretes an airy foam that males transfer to females during mating. We compared molecular evolutionary patterns among (1) genes with induced expression in breeding vs. wintering conditions for both tissues and (2) genes that encode foam proteins (FPs) vs. those with varying degrees of expression specificity in the FG. We report two major findings. First, genes upregulated in breeding condition testes evolve exceptionally rapidly, while those induced in breeding condition FGs evolve slowly. These differences hold even after correcting for hormonally-dependent gene expression and chromosomal location. Second, genes encoding FPs are extremely conserved in terms of gene identity and sequence. Together, these finding suggest that genes involved in the reproductive function of each tissue drive the marked rate of heterogeneity

Evolution of the Highly Repetitive PEVK Region of Titin Across Mammals

The protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin—named for its high proportion of Pro-Glu-Val-Lys amino acids—is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. The PEVK-C region can be further divided into a highly repetitive region (PEVK-CA) and one that is more variable (PEVK-CB). Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation

A Comparison of Next Generation Sequencing Technologies for Transcriptome Assembly and Utility for RNA-Seq in a Non-Model Bird

<div><p><i>De novo</i> assembled transcriptomes, in combination with RNA-Seq, are powerful tools to explore gene sequence and expression level in organisms without reference genomes. Investigators must first choose which high throughput sequencing platforms will provide data most suitable for their experimental goals. In this study, we explore the utility of 454 and Illumina sequences for <i>de novo</i> transcriptome assembly and downstream RNA-Seq applications in a reproductive gland from a non-model bird species, the Japanese quail (<i>Coturnix japonica</i>). Four transcriptomes composed of either pure 454 or Illumina reads or mixtures of read types were assembled and evaluated for the same cost. Illumina assemblies performed best for <i>de novo</i> transcriptome characterization in terms of contig length, transcriptome coverage, and complete assembly of gene transcripts. Improvements over the Hybrid assembly were marginal, with the exception that the addition of 454 data significantly increased the number of genes annotated. The Illumina assembly provided the best reference to align an independent set of RNA-Seq data as ∼84% of reads mapped to single genes in the transcriptome. Contigs constructed solely from 454 data may impose problems for RNA-Seq as our 454 transcriptome revealed a high number of indels and many ambiguously mapped reads. Correcting the 454 transcriptome with Illumina reads was an effective strategy to deal with indel and frameshift errors inherent to the 454 transcriptome, but at the cost of transcriptome coverage. In the absence of a reference genome, we find that Illumina reads alone produced a high quality transcriptome appropriate for RNA-Seq gene expression analyses.</p></div

Number and frequency of contigs with no open reading frames.

<p>Number and frequency of contigs with no open reading frames.</p

Distribution of contig lengths for each transcriptome assembly.

<p><b>a</b>) Histogram of contig lengths (natural-log transformed) in nucleotide base pairs of each of the transcriptome assemblies and the Chicken coding sequence set. <b>b</b>) Histogram of open reading frame lengths (natural-log transformed) in base pairs predicted for each of the transcriptome assemblies and the Chicken coding sequence set. Legend applies to both graphs.</p

Ortholog hit ratios for each transcriptome assembly.

<p>Histograms of ortholog hit ratios (<i>i.e.</i>, contig lengths relative to ortholog length) for contigs generated from the 454, Illumina, Corrected 454, and Hybrid transcriptome assemblies. Ratios equal to 1 indicate fully assembled transcripts. Values <1 signify partial transcripts and values >1 than represent contigs with insertions relative to orthologs. Orthologs were determined by 1∶1 reciprocal best blast hits with chicken.</p