Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

BACKGROUND: Retinal dystrophies (RD) are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES) as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context. METHODOLOGY/PRINCIPAL FINDINGS: We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations) in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases. CONCLUSIONS/SIGNIFICANCE: Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

A-1 Monthly Public Assistance Statistical Report Family Investment Program, April 2004

Monthly Public Assistance Statistical Report Family Investment Program

A-1 Monthly Public Assistance Statistical Report Family Investment Program, May 2004

Monthly Public Assistance Statistical Report Family Investment Program

La implicació de les famílies immigrades en els processos educatius dels seus fills/es: estratègies davant l'èxit i el fracàs escolar

En el present projecte hem analitzat els determinants de les trajectòries educatives dels i les adolescents d'origen immigrant, centrant I'atenció en el paper de les seves famílies davant de I ‘èxit o fracàs escolar del seu fillla. Amb aquest objectiu, I'estudi combina tècniques quantitatives i qualitatives. Per una banda hem analitzat les dades longitudinals del Panel de Famílies i lnfancia, que ens permeten fer un seguiment de les trajectòries educatives i personals de 248 alumnes d'origen immigrant que al 2006 estudiaven I'ESO al llarg de la seva adolescència, i identificar els factors socials responsables de la seva diversificació. Els resultats indiquen que malgrat presentar actituds bastant favorables als estudis i I'assoliment educatiu, concentren diverses situacions de vulnerabilitat a la llar (dificultats socioeconòmiques, estructures familiars atípiques, i erosió de capital social), que incideixen negativament sobre els seus rendiments acadèmics. Per altra, hem realitzat 59 entrevistes semi-estructurades per a complementar i facilitar la interpretació dels resultats obtinguts a la recerca quantitativa i copsar les narratives dels propis protagonistes. Aquestes entrevistes s'han realitzat a: una submostra de les famílies d'aquests alumnes, seleccionades en funció de perfils d’èxit o fracàs educatiu de la trajectòria del menor (46), una submostra d'estudiants resilients (a), i una sèrie d'agents educatius i socials, que inclou membres d'equips directius de centres escolars, AMPA i entitats dedicades a I'atenció a la infància i les famílies (5). El projecte que presentem té una clara vocació de servei públic. L'objectiu és incrementar el coneixement de factors "extraescolars" que poden condicionar I ‘èxit escolar dels estudiants d'origen immigrant. Aquest coneixement constitueix la base per al disseny i orientació de programes d'acompanyament a les famílies dels infants en situació de risc. La nostra voluntat (que reflecteix el principal objectiu de I'lnstitut d’infància i Món Urbà, instituci6 que impulsa el projecte) és contribuir a la transferència de coneixement que pugui ser d'utilitat pels agents que treballen directament sobre les qüestions que estudiem.

Iowa Federal Family Education Loan Program Division, Iowa College Student Aid Commission - Independent Auditor's Reports Basic Financial Statements and Supplementary Information, June 30, 2003

State Agency Audit Report

A-1 Monthly Public Assistance Statistical Report Family Investment Program, June 2004

Monthly Public Assistance Statistical Report Family Investment Program

Excessive alcohol consumption in young men: is there an association with their earlier family situation? A baseline-analysis of the C-SURF-study (Cohort Study on Substance Use Risk Factors).

AIMS: To determine whether parental factors earlier in life (parenting, single parent family, parental substance use problem) are associated with patterns of alcohol consumption among young men in Switzerland. METHODS: This analysis of a population based sample from the Cohort Study on Substance Use Risk Factors (C-SURF) included 5,990 young men (mean age 19.51 years), all attending a mandatory recruitment process for the army. These conscripts reported on parental monitoring and rule-setting, parental behaviour and family structure. The alcohol use pattern was assessed through abstention, risky single occasion drinking (RSOD), volume drinking and dependence. Furthermore, the impact of age, family socio-economic status, educational level of the parents, language region and civil status was analysed. RESULTS: A parental substance use problem was positively associated with volume drinking and alcohol dependence in young Swiss men. Active parenting corresponded negatively with RSOD, volume drinking and alcohol dependence. Single parent family was not associated with a different alcohol consumption pattern compared to standard family. CONCLUSION: Parental influences earlier in life such as active parenting (monitoring, rule-setting and knowing the whereabouts) and perceived parental substance use problem are associated with alcohol drinking behaviour in young male adults. Therefore, health professionals should stress the importance of active parenting and parental substance use prevention in alcohol prevention strategies.

Infrequent expression of the MAGE gene family in uveal melanomas.

It has previously been reported that MAGE-1, -2, -3 and -4 genes are expressed in human cancers including cutaneous melanoma. MAGE-1 and MAGE-3 represent targets for specific immunotherapy because they encode peptide antigens which are recognised by cytotoxic T lymphocytes (CTL) when presented by HLA class I molecules, and pilot clinical trials with these peptides are currently in progress. It is likely that other members of the MAGE gene family may also encode antigens recognised by CTL. Uveal melanomas, like cutaneous melanomas, arise from melanocytes that are derived from the neural crest. To determine if uveal melanoma patients would be suitable for MAGE-peptide immunotherapy, the expression of MAGE-1, -2, -3 and -4 genes was assessed by reverse transcription followed by polymerase chain reaction (RT-PCR) amplification and ethidium bromide staining. Expression of MAGE genes was not detected in any of 27 primary tumours. Either MAGE-1 or MAGE-4 was expressed in only 2 of 26 metastatic samples, but expression of MAGE-2 or -3 was not detected. Our data suggest that, unlike cutaneous melanomas, uveal melanomas may not be suitable candidates for MAGE-peptide immunotherapy.

Big brother is watching you: eavesdropping to resolve family conflicts

Adult animals can eavesdrop on behavioral interactions between potential opponents to assess their competitive ability and motivation to contest resources without interacting directly with them. Surprisingly, eavesdropping is not yet considered as an important factor used to resolve conflicts between family members. In this study, we show that nestling barn owls (Tyto alba) competing for food eavesdrop on nestmates' vocal interactions to assess the dominance status and food needs of opponents. During a first training playback session, we broadcasted to singleton bystander nestlings a simulated vocal interaction between 2 prerecorded individuals, 1 relatively old (i.e., senior) and 1 younger nestling (i.e., junior). One playback individual, the "responder," called systematically just after the "initiator" playback individual, hence displaying a higher hunger level. To test whether nestlings have eavesdropped on this interaction, we broadcasted the same prerecorded individuals separately in a subsequent playback test session. Nestlings vocalized more rapidly after former initiators' than responders' calls and they produced more calls when the broadcasted individual was formerly a junior initiator. They chiefly challenged vocally juniors and initiators against whom the likelihood of winning a vocal contest is higher. Owlets, therefore, identified the age hierarchy between 2 competitors based on their vocalizations. They also memorized the dynamics of competitors' previous vocal interactions, and used this information to optimally adjust signaling level once interacting with only 1 of the competitor. We conclude that siblings eavesdrop on one another to resolve conflicts over parental resources.

A-1 Monthly Public Assistance Statistical Report Family Investment Program, January 2002

Monthly Public Assistance Statistical Report Family Investment Program

A-1 Monthly Public Assistance Statistical Report Family Investment Program, December 2001

Monthly Public Assistance Statistical Report Family Investment Program

A-1 Monthly Public Assistance Statistical Report Family Investment Program, February 2002

Monthly Public Assistance Statistical Report Family Investment Program

A-1 Monthly Public Assistance Statistical Report Family Investment Program, March 2002

Monthly Public Assistance Statistical Report Family Investment Program

A-1 Monthly Public Assistance Statistical Report Family Investment Program, June 2003

Monthly Public Assistance Statistical Report Family Investment Program

What the Law Requires: Accessible Multi-family Housing in Iowa, 2003

Booklet produced by the Iowa Civil Rights Commission for individuals who own, design, build, or develop multi-family housing.