The Structure of Cognitive Abilities and Associations with Problem Behaviors in Early Adolescence: An Analysis of Baseline Data from the Adolescent Brain Cognitive Development Study.

Using baseline data (n = 9875) from the Adolescent Brain Cognitive Development (ABCD) Study examining children aged 9 to 10 years, the current analyses included: (1) exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of neurocognitive measures administered during baseline collection, and (2) linear regression analyses on the Child Behavior Checklist (CBCL), controlling for demographic and socioeconomic factors. The neurocognitive tasks measured episodic memory, executive function (EF; attention), language skills, processing speed, working memory, visuospatial ability, and reasoning. The CBCL included composite scores of parent-reported internalizing, externalizing, and stress-related behavior problems. The study reported here serves as an extension of prior research using a principal components analysis (PCA) of the ABCD baseline data. We propose an alternative solution using factor analysis. Analyses revealed a three-factor structure: verbal ability (VA), executive function/processing speed (EF/PS), and working memory/episodic memory (WM/EM). These factors were significantly correlated with the CBCL scores, albeit with small effect sizes. These findings provide a novel three-factor solution to the structure of cognitive abilities measured in the ABCD Study, offering new insights into the association between cognitive function and problem behaviors in early adolescence.

Seeing double: 5-month-olds' mental rotation of dynamic, 3D block stimuli presented on dual monitors.

Mental rotation (MR) involves the ability to predict how an object will look once it has been rotated into a new orientation in space. To date, studies of MR in infants have tested this ability using abstract stimuli presented using a single display. Evidence from existing studies suggests that using multiple displays may affect an infant's performance in some kinds of MR tasks. This study used Moore & Johnson's (2008) simplified Shepard-Metzler objects in a dual-monitor MR task presented to five-month-old infants. Evidence for MR in infancy was found. These findings have implications for MR testing in infancy and the influence of display properties on infant MR performance.

Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation.

STUDY OBJECTIVE: To evaluate the steady-state pharmacokinetic parameters of standard cefepime dosing regimens in a hematologic malignancy and hematopoietic cell transplant patient population with febrile neutropenia. DESIGN: Open-label, single-center, prospective pharmacokinetic study. SETTING: National Cancer Institute-designated cancer center. PATIENTS: Nine adults with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia and were admitted to a hematology-oncology service between January and July 2014. INTERVENTION: Patients received empirical cefepime 2 g every 8 hours, administered as a 30-minute intravenous infusion, for febrile neutropenia. MEASUREMENTS AND MAIN RESULTS: Steady-state cefepime serum concentrations were measured after at least 2 days of continuous therapy. Venous blood samples were intensively sampled between 0 and 8 hours after the start of the 30-minute infusion at steady state. Seven of the nine patients had a hematologic malignancy diagnosis of acute leukemia, lymphoma, or myeloma, and two patients had a germ cell tumor diagnosis. Noncompartmental analysis revealed mean ± SD parameters as follows at steady state: area under the plasma concentration-time curve from 0-8 hours 222.9 ± 72.9 mg hour/L, maximum concentration 120.9 ± 21.8 mg/L, clearance 9.7 ± 3.7 L/hour, apparent volume of distribution 19.2 ± 4.65 L, and elimination half-life 1.4 ± 0.3 hours. A one-compartment pharmacokinetic model identified a mean ± SD volume of distribution of 20.9 ± 1.3 L and an elimination rate constant of 0.39 ± 0.03 hour(-1) . The mean estimated percentage of time that drug concentration remains above the pathogen minimum inhibitory concentration (fT>MIC) in serum was 55%, 77%, and 99% at MICs of 16, 8, and 4 mg/L, respectively. CONCLUSION: Patients with hematologic malignancies or hematopoietic cell transplants who had febrile neutropenia demonstrated homogeneous calculated cefepime volumes and clearances. The population parameters presented in this study may aid in the calculation of patient-specific fT>MIC for similar patients.

Treatment of cocaine abuse during pregnancy: translating research to clinical practice.

In the late-1980s and early-1990s, much attention in America was focused on cocaine abuse. In particular, the effects of prenatal cocaine use on mothers and infants were in the news spotlight. Risks of adverse effects prompted funding for novel treatment programs. More recently, media attention has shifted elsewhere, and specialized treatment resources have grown scarce. This redirection of funding is unfortunate, as social stigma and fear of legal consequences continue to encourage cocaine-abusing pregnant women to hide drug use and avoid prenatal care. The purpose of this article is to summarize the most prominent adverse maternal and fetal/infant effects associated with prenatal cocaine use; review treatment options, focusing on comprehensive care programs of the 1990s as well as recent research on evidence-based practices and their applicability to pregnant women; and highlight the population of prenatal cocaine-abusing women uninterested in treatment, with a focus on promising strategies to promote drug abstinence and other positive health behaviors.

How can we help witnesses to remember more? It's an (eyes) open and shut case.

Five experiments tested the idea that instructing a witness to close their eyes during retrieval might increase retrieval success. In Experiment 1 participants watched a video, before a cued-recall test for which they were either instructed to close their eyes, or received no-instructions. Eye-closure led to an increase in correct cued-recall, with no increase in incorrect responses. Experiments 2-5 sought to test the generality of this effect over variations in study material (video or live interaction), test format (cued- or free-recall) and information modality (visual or auditory details recalled). Overall, eye-closure increased recall of both visual detail and auditory details, with no accompanying increase in recall of false details. Collectively, these data convincingly demonstrate the benefits of eye-closure as an aid to retrieval, and offer insight into why hypnosis, which usually involves eye-closure, may facilitate eyewitness recall.

A yeast recombination-based cloning system to produce chimeric HIV-1 viruses and express HIV-1 genes.

Differential phenotypes or properties of HIV-1 gene products in primary virus isolates are difficult to assess due to interference by the high degree of sequence variation across the entire genome. Thus, chimeric viruses provide a powerful tool to study the function of single gene products or genetic elements in the context of a neutral viral genomic backbone. In this chapter, we describe how to produce HIV-1 chimeric viruses utilizing a yeast-based homologous recombination cloning technique to insert env sequences first into a yeast cloning vector and then into the common pNL4-3 virus backbone. This technique is not limited to the env gene, but can be used to build chimeric viruses with any HIV-1 gene or genetic element. This cloning technique involves the use of a shuttle vector that can replicate in yeast and bacterial cells. Along with acting as a shuttle vector for subsequent subcloning into pNL4-3, this construct pRec/env can also be used to express to the env gene product, gp120/gp41, on the surface of mammalian cells. The chimeric viruses produced by this cloning method are capable of undergoing multiple rounds of replication and are therefore very useful to study drug sensitivity, coreceptor usage, and viral fitness as influenced by a single gene or gene fragment of a primary HIV-1 isolate from any group M subtype.

Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression.

This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.

Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry.

The ability of one primary human immunodeficiency virus type 1 (HIV-1) isolate to outcompete another in primary CD4+ human lymphoid cells appears to be mediated by the efficiency of host cell entry. This study was designed to test the role of entry on fitness of wild-type HIV-1 isolates (e.g., replicative capacity) and to examine the mechanism(s) involved in differential entry efficiency. The gp120 coding regions of two diverse HIV-1 isolates (the more-fit subtype B strain, B5-91US056, and less-fit C strain, C5-97ZA003) were cloned into a neutral HIV-1 backbone by using a recently described yeast cloning technique. The fitness of the primary B5 HIV-1 isolates and its env gene cloned into the NL4-3 laboratory strain had similar fitness, and both were more fit than the C5 primary isolate and its env/NL4-3 chimeric counterpart. Increased fitness of the B5 over C5 virus was mediated by the gp120 coding region of the env gene. An increase in binding/fusion, as well as decreased sensitivity to entry inhibitors (PSC-RANTES and T-20), was observed in cell fusion assays mediated by B5 gp120 compared to C5 gp120. Competitive binding assays using a novel whole virus-cell system indicate that the primary or chimeric B5 had a higher avidity for CD4/CCR5 on host cells than the C5 counterpart. This increased avidity of an HIV-1 isolate for its cell receptors may be a significant factor influencing overall replicative capacity or fitness.

Relationships between infectious titer, capsid protein levels, and reverse transcriptase activities of diverse human immunodeficiency virus type 1 isolates.

Most studies on human immunodeficiency virus type 1 (HIV-1) replication kinetics or fitness must rely on a particular assay to initially standardize inocula from virus stocks. The most accurate measure of infectious HIV-1 titers involves a limiting dilution-infection assay and a calculation of the dose required for 50% infectivity of susceptible cells in tissue culture (TCID(50)). Surrogate assays are now commonly used to measure the amount of p24 capsid, the endogenous reverse transcriptase (RT) activity, or the amount of viral genomic RNA in virus particles. However, a direct comparison of these surrogate assays and actual infectious HIV-1 titers from TCID(50) assays has not been performed with even the most conserved laboratory strains, let alone the highly divergent primary HIV-1 isolates of different subtypes. This study indicates that endogenous RT activity, not p24 content or viral RNA load, is the best surrogate measure of infectious HIV-1 titer in both cell-free supernatants and viruses purified on sucrose cushions. Sequence variation between HIV-1 subtypes did not appear to affect the function or activity of the RT enzyme in this endogenous assay but did affect the detection of p24 capsid by both enzyme immunoassays and Western blots. Clear groupings of non-syncytium-inducing (NSI), CCR5-tropic (R5), and SI/CXCR4-tropic (X4) HIV-1 isolates were observed when we compared the slopes derived from correlations of RT activity with infectious titers. Finally, the replication efficiency or fitness of both the NSI/R5 and SI/X4 HIV-1 isolates was not linked to the titers of the virus stocks.