Formation and Evolution of Planetary Systems: Placing Our Solar System in Context with Spitzer

We summarize the progress to date of our Legacy Science Program entitled "The Formation and Evolution of Planetary Systems" (FEPS) based on observations obtained with the Spitzer Space Telescope during its first year of operation. In addition to results obtained from our ground-based preparatory program and our early validation program, we describe new results from a survey for near-infrared excess emission from the youngest stars in our sample as well as a search for cold debris disks around sun-like stars. We discuss the implications of our findings with respect to current understanding of the formation and evolution of our own solar system.Comment: 8 postscript pages including 3 figures. To appear in "Spitzer New Views of the Cosmos" ASP Conference Series, eds. L. Armus et al. FEPS website at http://feps.as.arizona.ed

Pregnancy Exposure Registries for Assessing Antimalarial Drug Safety in Pregnancy in Malaria-Endemic Countries

Feiko ter Kuile and colleagues argue that there is an urgent need to develop targeted pharmacovigilance systems to assess the safety of antimalarials in early pregnancy

Identification of FOXP1 Deletions in Three Unrelated Patients with Mental Retardation and Significant Speech and Language Deficits

Mental retardation affects 2-3% of the population and shows a high heritability. Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors. We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletions or duplications. These studies revealed three heterozygous overlapping deletions solely affecting the forkhead box P1 (FOXP1) gene. All three patients had moderate mental retardation and significant language and speech deficits. Since our results are consistent with a de novo occurrence of these deletions, we considered them as causal although we detected a single large deletion including FOXP1 and additional genes in 4104 ancestrally matched controls. These findings are of interest with regard to the structural and functional relationship between FOXP1 and FOXP2. Mutations in FOXP2 have been previously related to monogenic cases of developmental verbal dyspraxia. Both FOXP1 and FOXP2 are expressed in songbird and human brain regions that are important for the developmental processes that culminate in speech and language. ©2010 Wiley-Liss, Inc

Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites

Downstream in-frame start codons produce amino-terminal-truncated human constitutive androstane receptor protein isoforms (ΔNCARs). The ΔNCARs are expressed in liver and in vitro cell systems following translation from in-frame methionine AUG start codons at positions 76, 80, 125, 128, 168 and 265 within the full-length CAR mRNA. The resulting CAR proteins lack the N-terminal DNA-binding domain (DBD) of the receptor, yielding ΔNCAR variants with unique biological function. Although the ΔNCARs maintain full retinoid X receptor alpha (RXRα) heterodimerization capacity, the ΔNCARs are inactive on classical CAR-inducible direct repeat (DR)-4 elements, yet efficiently transactivate a DR-1 element derived from the endogenous PPAR-inducible acyl-CoA oxidase gene promoter. RXRα heterodimerization with CAR1, CAR76 and CAR80 isoforms is necessary for the DR-1 PPRE activation, a function that exhibits absolute dependence on both the respective RXRα DBD and CAR activation (AF)-2 domains, but not the AF-1 or AF-2 domain of RXRα, nor CAR's DBD. A new model of CAR DBD-independent transactivation is proposed, such that in the context of a DR-1 peroxisome proliferator-activated response element, only the RXRα portion of the CAR-RXRα heterodimer binds directly to DNA, with the AF-2 domain of tethered CAR mediating transcriptional activation of the receptor complex

Core functions of a financial navigation intervention: An in-depth assessment of the Lessening the Impact of Financial Toxicity (LIFT) intervention to inform adaptation and scale-up in diverse oncology care settings

Background Lessening the Impact of Financial Toxicity (LIFT) is an intervention designed to address financial toxicity (FT) and improve cancer care access and outcomes through financial navigation (FN). FN identifies patients at risk for FT, assesses eligibility for financial support, and develops strategies to cope with those costs. LIFT successfully reduced FT and improved care access in a preliminary study among patients with high levels of FT in a single large academic cancer center. Adapting LIFT requires distinguishing between core functions (components that are key to its implementation and effectiveness) and forms (specific activities that carry out core functions). Our objective was to complete the first stage of adaptation, identifying LIFT core functions. Methods We reviewed LIFT's protocol and internal standard-operating procedures. We then conducted 45–90 min in-depth interviews, using Kirk's method of identifying core functions, with key LIFT staff (N = 8), including the principal investigators. Interviews focused on participant roles and intervention implementation. Recorded interviews were transcribed verbatim. Using ATLAS.ti and a codebook based on the Model for Adaptation Design and Impact, we coded interview transcripts. Through thematic analysis, we then identified themes related to LIFT's intervention and implementation core functions. Two report back sessions with interview participants were incorporated to further refine themes. Results Six intervention core functions (i.e., what makes LIFT effective) and five implementation core functions (i.e., what facilitated LIFT's implementation) were identified to be sufficient to reduce FT. Intervention core functions included systematically cataloging knowledge and tracking patient-specific information related to eligibility criteria for FT relief. Repeat contacts between the financial navigator and participant created an ongoing relationship, removing common barriers to accessing resources. Implementation core functions included having engaged sites with the resources and willingness necessary to implement FN. Developing navigators' capabilities to implement LIFT—through training, an established case management system, and connections to peer navigators—were also identified as implementation core functions. Conclusion This study adds to the growing evidence on FN by characterizing intervention and implementation core functions, a critical step toward promoting LIFT's implementation and effectiveness

Fine-scale spatial segregation in a pelagic seabird driven by differential use of tidewater glacier fronts

In colonially breeding marine predators, individual movements and colonial segregation are influenced by seascape characteristics. Tidewater glacier fronts are important features of the Arctic seascape and are often described as foraging hotspots. Albeit their documented importance for wildlife, little is known about their structuring effect on Arctic predator movements and space use. In this study, we tested the hypothesis that tidewater glacier fronts can influence marine bird foraging patterns and drive spatial segregation among adjacent colonies. We analysed movements of black-legged kittiwakes (Rissa tridactyla) in a glacial fjord by tracking breeding individuals from five colonies. Although breeding kittiwakes were observed to travel up to ca. 280 km from the colony, individuals were more likely to use glacier fronts located closer to their colony and rarely used glacier fronts located farther away than 18 km. Such variation in the use of glacier fronts created fine-scale spatial segregation among the four closest (ca. 7 km distance on average) kittiwake colonies. Overall, our results support the hypothesis that spatially predictable foraging patches like glacier fronts can have strong structuring effects on predator movements and can modulate the magnitude of intercolonial spatial segregation in central-place foragers

PRNP Haplotype Associated with Classical BSE Incidence in European Holstein Cattle

Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE. Methodology/Principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPs) within PRNP were used to test for association between PRNP haplotypes and BSE disease. A combination of Illumina goldengate assay, sequencing and PCR amplification was used to genotype 18 htSNPs and 2 indels in 95 BSE case and 134 control animals. A haplotype within the region of high LD was found to be associated with BSE unaffected animals (p-value = 0.000114). Conclusion/Significance: A PRNP haplotype association with classical BSE incidence has been identified. This result suggests that a genetic determinant in or near PRNP may influence classical BSE incidence in cattle