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Purpose : ASD is associated with relative strengths in the visuospatial domain but varying abilities in the linguistic domain. Previous studies suggest parallels between spatial language and spatial cognition in older autistic individuals, but no research to date has examined this relationship in young autistic children. Therefore, the purpose of the present study was to investigate the connection between children’s spatial language production and nonverbal spatial cognition over time. We also examined two potential predictors of spatial language observed in previous literature, ASD symptom severity and parent spatial language input. Methods : In past work investigating spatial language in NT children of the same age, parent-child interactions have been a primary context for study. Therefore, in the present study, we analyzed transcripts of dyadic naturalistic play interactions between autistic children and their parents over three visits from age 30 to 66 months and administered standardized cognitive and ASD diagnostic assessments at each visit. Results : Spatial language production was related to nonverbal spatial cognition even when accounting for overall language production, though the strength of that relationship decreased over time. Parent spatial input (but not ASD severity) significantly predicted children’s spatial language production over and above the effect of overall language production. Conclusion : Spatial language is associated with spatial cognition in young autistic children and appears to reflect the interaction of overall linguistic skills and nonverbal spatial cognitive ability regardless of autism severity. Parent-mediated interventions may be a promising context for increasing spatial language in autistic preschoolers.

Recent theoretical accounts suggest that differences in the processing of probabilistic events underlie the core and associated traits of autism spectrum disorder (ASD). These theories hypothesize that autistic individuals are differentially impacted by disruptions in probabilistic input relative to neurotypical peers. According to this view, autistic individuals assign disproportionate weight to prediction errors such that novel input is overweighted relative to the aggregation of prior input; this is referred to as 'hyperplasticity' of learning. Prediction among autistic individuals has primarily been examined in nonverbal, visual contexts with older children and adults. The present study examined 32 autistic and 32 cognitively-matched neurotypical (NT) children's ability to generate predictions and adjust to changes in predictive relationships in auditory stimuli using two eye gaze tasks. In both studies, children were trained and tested on an auditory-visual cue which predicted the location of a reward stimulus. In Experiment 1 the cue was non-linguistic (instrumental sound) whereas in Experiment 2 the cue was linguistically-relevant (speaker gender). In both experiments, the cue-reward contingency was switched after the first block of trials, and predictive behavior was evaluated across a second block of trials. Analyses of children's looking behavior revealed similar performance in both groups on the non-linguistic task (Exp. 1). In the linguistically-relevant task (Exp. 2), predictive looking was less disrupted by the contingency switch for autistic children than NT children. Results suggest that autistic children may demonstrate hyperplastic learning in linguistically-relevant contexts, relative to NT peers.

This study investigated receptive and expressive language outcomes in children with autism spectrum disorder (ASD) with and without a history of language/communication regression, employing three progressively less stringent definitions of regression. Data were derived from a large, longitudinal sample of children with ASD in which regression was assessed at approximately 30 months. Results indicated poorer receptive language and larger discrepancies between receptive and expressive language in the regression group than the group without regression at 44 months but not 66 months. Number of words used before loss predicted receptive language at 44 months. Overall, results suggest that a regression profile in ASD is associated with modest and transient impacts on language outcomes that are no longer discernable at school entry.

What cognitive mechanisms allow young autistic children to learn words amidst the complexity of natural language environments? This dissertation sought to inform this question by investigating the ability of 2- to 4-year-old autistic children and neurotypical (NT) peers to learn words by tracking statistical co-occurrences between labels and referents across multiple contexts (i.e., cross-situational learning (CSL). While previous CSL studies examined children’s ability to map each novel word to a single object, in natural environments children must track the co-occurrences between novel words and the many objects to which that word may refer. Thus, to elucidate the extent to which autistic children can harness cross-situational statistics to learn words referring to perceptually variable objects, I also administered a CSL task that included three exemplars varying in color for each novel word. I further examined whether explicit naming would improve word learning from variable exemplars. Finally, I investigated child characteristics predictive of individual differences in word learning across these conditions among autistic children. Analyses revealed that while autistic children did not show evidence of learning in the basic CSL task, they did demonstrate learning in the CSL task with exemplar variability. Further, they outperformed younger NT children on the task when nonverbal cognition was covaried. Explicit naming of variable exemplars did not improve performance for the autistic children and improved performance in the NT children to a greater extent compared to autistic children. Individual differences analyses revealed receptive language was associated with autistic children’s performance in the basic CSL task and chronological age was associated with performance when variable exemplars were explicitly named. In sum, results indicated that preschool-age autistic children as a group could successfully use cross-situational statistics to learn words with (but not without) exemplar variability, and that learning was not improved by explicit naming. However, within-group variability in word learning was evident across tasks, explained in part by individual differences in receptive language and chronological age. More research will be needed to fully understand the mechanisms underlying this surprising pattern of findings, which might include the extent to which visual attention is directed by the perceptual salience of stimuli. While preliminary, these findings may inform future research, clinical practice, and environmental accommodations tailored to the individual strengths and needs of young autistic children.

Two risk-averse litigants with different subjective beliefs negotiate in the shadow of a pending trial. Through contingent contracts, the litigants can mitigate risk and/or speculate on the trial outcome. Contingent contracting decreases the settlement rate and increases the volume and costs of litigation. These contingent contracts mimic the services provided by third-party investors, including litigation funders and insurance companies. The litigants (weakly) prefer to contract with risk-neutral third parties when the capital market is transaction-cost free. However, contracting with third parties further decreases the settlement rate, increases the costs of litigation, and may increase the aggregate cost of risk bearing.

This article presents the first systematic theoretical and empirical study of high-low agreements in civil litigation. A high-low agreement is a private contract that, if signed by litigants before trial, constrains any plaintiff’s recovery to a specified range. In our theoretical model, trial is both costly and risky. When litigants have divergent subjective beliefs and are mutually optimistic about their trial prospects, cases may fail to settle. In these cases, high-low agreements can be in litigants’ mutual interest because they limit the risk of outlier awards while still allowing mutually beneficial speculation. Using claims data from a national insurance company, we describe the features of these agreements and empirically investigate the factors that may influence whether litigants discuss or enter into them. Our empirical findings are consistent with the predictions of the theoretical model. Other applications include the use of collars in mergers and acquisitions.

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.

Background. The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus. Methods. All blood samples from suspected Ebola virus–infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus–infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia. Results. The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus–infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model. Conclusions. Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

In this trial involving patients with mild, persistent asthma, there was no significant difference in therapeutic effect between an inhaled glucocorticoid (mometasone) and placebo in patients with a low sputum eosinophil level (<2%), which was reported in nearly three quarters of the patients.

West Africa experienced the first epidemic of Ebola virus infection, with by far the greatest number of cases in Guinea, Sierra Leone, and Liberia. The unprecedented epidemic triggered an unparalleled response, including the deployment of multiple Ebola treatment units and mobile/field diagnostic laboratories. The National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention deployed a joint laboratory to Monrovia, Liberia, in August 2014 to support the newly founded Ebola treatment unit at the Eternal Love Winning Africa (ELWA) campus. The laboratory operated initially out of a tent structure but quickly moved into a fixed-wall building owing to severe weather conditions, the need for increased security, and the high sample volume. Until May 2015, when the laboratory closed, the site handled close to 6000 clinical specimens for Ebola virus diagnosis and supported the medical staff in case patient management. Laboratory operation and safety, as well as Ebola virus diagnostic assays, are described and discussed; in addition, lessons learned for future deployments are reviewed.