National Health Expenditure Projections, 2023-32: Payer Trends Diverge As Pandemic-Related Policies Fade.

Health care spending growth is expected to outpace that of the gross domestic product (GDP) during the coming decade, resulting in a health share of GDP that reaches 19.7 percent by 2032 (up from 17.3 percent in 2022). National health expenditures are projected to have grown 7.5 percent in 2023, when the COVID-19 public health emergency ended. This reflects broad increases in the use of health care, which is associated with an estimated 93.1 percent of the population being insured that year. In 2024, Medicaid enrollment is projected to decline significantly as states continue their eligibility redeterminations. Simultaneously, private health insurance enrollment is projected to increase because of the extension of enhanced subsidies for direct-purchase health insurance under the Inflation Reduction Act (IRA) of 2022, as well as a temporary special enrollment period for qualified people losing Medicaid coverage (after eligibility redeterminations). Over the course of 2024-26, the IRA expands Medicare's drug benefit generosity and implements drug price negotiations for beneficiaries; concurrently, the extended enhanced subsidies for direct-purchase health insurance expire in 2026. During 2027-32, personal health care price inflation and growth in the use of health care services and goods contribute to projected health spending that grows at a faster rate than the rest of the economy.

Perseveration on a reversal-learning task correlates with rates of self-directed behavior in nonhuman primates.

In humans and several nonhuman animals, repetitive behavior is associated with deficits on executive function tasks involving response inhibition. We tested for this relationship in nonhuman primates by correlating rates of normative behavior to performance on a reversal-learning task in which animals were required to inhibit a previously learned rule. We focused on rates of self-directed behavior (scratch, autogroom, self touch and manipulation) because these responses are known indicators of arousal or anxiety in primates, however, we also examined rates of other categories of behavior (e.g., locomotion). Behavior rates were obtained from 14 animals representing three nonhuman primate species (Macaca silenus, Saimiri sciureus, Cebus apella) living in separate social groups. The same animals were tested on a reversal-learning task in which they were presented with a black and a grey square on a touch screen and were trained to touch the black square. Once animals learned to select the black square, reward contingencies were reversed and animals were rewarded for selecting the grey square. Performance on the reversal-learning task was positively correlated to self-directed behavior in that animals that exhibited higher rates of self-directed behavior required more trials to achieve reversal. Reversal learning was not correlated to rates of any other category of behavior. Results indicate that rates of behavior associated with anxiety and arousal provide an indicator of executive function in nonhuman primates. The relationship suggests continuity between nonhuman primates and humans in the link between executive functioning and repetitive behavior.

Reciprocal fusion transcripts of two novel Zn-finger genes in a female with absence of the corpus callosum, ocular colobomas and a balanced translocation between chromosomes 2p24 and 9q32.

We have identified a female patient with a complex phenotype that includes complete agenesis of the corpus callosum, bilateral periventricular nodular heterotopia, and bilateral chorioretinal and iris colobomas. Karyotype analysis revealed an apparently balanced, reciprocal, de novo chromosome translocation t(2;9)(p24;q32). Physical mapping of the translocation breakpoint by fluorescence in situ hybridization and PCR analysis led to the identification of two novel, ubiquitously expressed, Zn-finger-encoding transcripts that are disrupted in this patient. Unexpectedly, the rearrangement produced in-frame reciprocal fusion transcripts, making genotype-phenotype correlation difficult.

Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3.

Deletions of 17p13.3, including the LIS1 gene, result in the brain malformation lissencephaly, which is characterized by reduced gyration and cortical thickening; however, the phenotype can vary from isolated lissencephaly sequence (ILS) to Miller-Dieker syndrome (MDS). At the clinical level, these two phenotypes can be differentiated by the presence of significant dysmorphic facial features and a more severe grade of lissencephaly in MDS. Previous work has suggested that children with MDS have a larger deletion than those with ILS, but the precise boundaries of the MDS critical region and causative genes other than LIS1 have never been fully determined. We have completed a physical and transcriptional map of the 17p13.3 region from LIS1 to the telomere. Using fluorescence in situ hybridization, we have mapped the deletion size in 19 children with ILS, 11 children with MDS, and 4 children with 17p13.3 deletions not involving LIS1. We show that the critical region that differentiates ILS from MDS at the molecular level can be reduced to 400 kb. Using somatic cell hybrids from selected patients, we have identified eight genes that are consistently deleted in patients classified as having MDS. In addition, deletion of the genes CRK and 14-3-3 epsilon delineates patients with the most severe lissencephaly grade. On the basis of recent functional data and the creation of a mouse model suggesting a role for 14-3-3 epsilon in cortical development, we suggest that deletion of one or both of these genes in combination with deletion of LIS1 may contribute to the more severe form of lissencephaly seen only in patients with MDS.

The evolutionary origin of human subtelomeric homologies--or where the ends begin.

The subtelomeric regions of human chromosomes are comprised of sequence homologies shared between distinct subsets of chromosomes. In the course of developing a set of unique human telomere clones, we identified many clones containing such shared homologies, characterized by the presence of cross-hybridization signals on one or more telomeres in a fluorescence in situ hybridization (FISH) assay. We studied the evolutionary origin of seven subtelomeric clones by performing comparative FISH analysis on a primate panel that included great apes and Old World monkeys. All clones tested showed a single hybridization site in Old World monkeys that corresponded to one of the orthologous human sites, thus indicating the ancestral origin. The timing of the duplication events varied among the subtelomeric regions, from approximately 5 to approximately 25 million years ago. To examine the origin of and mechanism for one of these subtelomeric duplications, we compared the sequence derived from human 2q13--an ancestral fusion site of two great ape telomeric regions--with its paralogous subtelomeric sequences at 9p and 22q. These paralogous regions share large continuous homologies and contain three genes: RABL2B, forkhead box D4, and COBW-like. Our results provide further evidence for subtelomeric-mediated genomic duplication and demonstrate that these segmental duplications are most likely the result of ancestral unbalanced translocations that have been fixed in the genome during recent primate evolution.