Extending Foster Care to Age 21: Weighing the Costs to Government against the Benefits to Youth

The Fostering Connections to Success and Increasing Adoptions Act of 2008 allows states to claim federal reimbursement for the costs of caring for and supervising Title IV-E eligible foster youth until their 21st birthday. This issue brief provides preliminary estimates of what the potential costs to government and the benefits to young people would be if states extend foster care to age 21. The analysis focuses on the increase in postsecondary educational attainment associated with allowing foster youth to remain in care until they are 21 years old and the resulting increase in lifetime earnings associated with postsecondary education. Researchers estimate that lifetime earnings would increase an average of two dollars for every dollar spent on keeping foster youth in care beyond age 18

The Inferior Temporal Numeral Area distinguishes numerals from other character categories during passive viewing: A representational similarity analysis

A region in the posterior inferior temporal gyrus (pITG) is thought to be specialized for processing Arabic numerals, but fMRI studies that compared passive viewing of numerals to other character types (e.g., letters and novel characters) have not found evidence of numeral preference in the pITG. However, recent studies showed that the engagement of the pITG is modulated by attention and task contexts, suggesting that passive viewing paradigms may be ill-suited for examining numeral specialization in the pITG. It is possible, however, that even if the strengths of responses to different category types are similar, the distributed response patterns (i.e., neural representations) in a candidate numeral-preferring pITG region ( pITG-numerals ) may reveal categorical distinctions, even during passive viewing. Using representational similarity analyses with three datasets that share the same task paradigm and stimulus sets (total N = 88), we tested whether the neural representations of digits, letters, and novel characters in pITG-numerals were organized according to visual form and/or conceptual categories (e.g., familiar versus novel, numbers versus others). Small-scale frequentist and Bayesian meta-analyses of our dataset-specific findings revealed that the organization of neural representations in pITG-numerals is unlikely to be described by differences in abstract shape, but can be described by a categorical digits versus letters distinction, or even a digits versus others distinction (suggesting greater numeral sensitivity). Evidence of greater numeral sensitivity during passive viewing suggest that pITG-numerals is likely part of a neural pathway that has been developed for automatic processing of objects with potential numerical relevance. Given that numerals and letters do not differ categorically in terms of shape, categorical distinction in pITG-numerals during passive viewing must reflect ontogenetic differentiation of symbol set representations based on repeated usage of numbers and letters in differing task contexts

A meta-analysis of functional reading systems in typically developing and struggling readers across different alphabetic languages

Functional neuroimaging research has identified multiple brain regions supporting reading-related activity in typical and atypical readers across different alphabetic languages. Previous meta-analyses performed on these functional magnetic resonance imaging findings typically report significant between-group contrasts comparing typical readers and readers with reading difficulty or a clinical diagnosis of developmental dyslexia. In order to advance our understanding of cross-linguistic convergence of reading-related brain activations for these reader groups, analyses using activation likelihood estimation were carried out separately for typical and atypical readers who ranged from children to adults. Contrasts were analyzed for tasks involving rhyming or reading of letter or word stimuli presented visually in English, Dutch, Italian, German, French, or Norwegian. Typical readers showed reliable activation in only left lateralized regions, including the inferior frontal area, precentral area and middle temporal gyrus. Atypical readers also showed activation in the left inferior frontal area and precentral region, in addition to significant activations in the right hemisphere, including the superior, medial and inferior frontal regions, lingual gyrus and the inferior occipital area. These results distinguish between typical and atypical reader group activations, showing common and distinct regions of activation when engaged in reading-related activities, extending previous meta-analyses on identifying brain regions relevant to reading to include cross-linguistic analyses for alphabetic scripts. Results support the universality of a signature pattern of brain activation in developmental dyslexia across alphabetic languages

Learning from Comparison in Algebra

Mastery of algebra is an important yet difficult milestone for students, suggesting the need for more effective teaching strategies in the algebra classroom. Learning by comparing worked-out examples of algebra problems may be one such strategy. Comparison is a powerful learning tool from cognitive science that has shown promising results in prior small-scale studies in mathematics classrooms. This study reports on a yearlong randomized controlled trial testing the effect of an Algebra I supplemental comparison curriculum on students’ mathematical knowledge. 141 Algebra I teachers were randomly assigned to either implement the comparison curriculum as a supplement to their regular curriculum or to be a ‘business as usual’ control. Use of the supplemental curriculum was much less frequent than requested for many teachers, and there was no main effect of condition on student achievement. However, greater use of the supplemental curriculum was associated with greater procedural student knowledge. These findings suggest a role for comparison in the algebra classroom but also the challenges of supporting teacher integration of new materials into the curriculum

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Same-Different Judgments With Alphabetic Characters: The Case of Literal Symbol Processing

Learning mathematics requires fluency with symbols that convey numerical magnitude. Algebra and higher-level mathematics involve literal symbols, such as "x", that often represent numerical magnitude. Compared to other symbols, such as Arabic numerals, literal symbols may require more complex processing because they have strong pre-existing associations in literacy. The present study tested this notion using same-different tasks that produce less efficient judgments for different magnitudes that are closer together compared to farther apart (i.e., same-different distance effects). Twenty-four adolescents completed three same-different tasks using Arabic numerals, literal symbols, and artificial symbols. All three symbolic formats produced same-different distance effects, showing literal and artificial symbol processing of numerical magnitude. Importantly, judgments took longer for literal symbols than artificial symbols on average, suggesting a cost specific to literal symbol processing. Taken together, results suggest that literal symbol processing differs from processing of other symbols that represent numerical magnitude