Evaluation Research: Some Possible Contexts of Theory Failure

What can evaluation research tell us about social science theory? It is the purpose of this paper to examine that question. There has been much written in the current literature about the relationship between theory and practice. Because it is evaluation research (Breedlove, 1972: 71-89; Newbrough, 1966: 39-52; Suchman, 1971: 43-48; Suchman, 1967; Weiss, 1973: 37-45; Fitz- Gibbons and Morris, 1975: 1-4) that attempts to analyze the results of practice, it is the authors\u27 belief that an examination of evaluation research studies for possible contexts of theory failure will contribute to a linkage between theory and practice

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

52 Genetic Loci Influencing Myocardial Mass.

BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets

Families Affected by Substance Abuse

A generalist approach to practice with families affected by parental addiction is presented. Using a model program for working with parents and children who have been affected by substance abuse, the article illustrates the application of the problem-solving process to effect change at multiple levels, including individual, family, community, organizational, and policy-making levels. The authors describe assessment and intervention strategies at each of these levels and conclude with an evaluation of the project\u27s success

Down Syndrome: Interaction between Culture, Demography, and Biology in Determining the Prevalence of a Genetic Trait

The incidence of Down syndrome (DS) at conception is highly dependent upon the maternal age distribution and age-specific pregnancy rates. Live-birth prevalence of DS reflects these factors and fetal deaths. Since the introduction of prenatal diagnosis in the early 1970s, the role of fetal deaths in the equation has increased. Between 1920 and the early 1980s, DS live-birth prevalence decreased in many populations due to declining fertility rates, particularly among older women. In the late-1970s the trend reversed, as the median age of populations and birth rates among older women steadily increased. This paper illustrates these interactions using data we have analyzed for New York State (NYS) and comparative data obtained from the literature. Between 1983 and 1997 DS live-birth prevalence in NYS remained stable at about 9.9 per 10,000 live births. The number of prenatal tests performed increased by 158%, and the number of DS fetuses detected prenatally more than quadrupled. Fertility rates of women aged 35–49 continued to increase. The proportion of DS cases born to these older mothers increased from 23% in 1985 to 43% in 1997. We estimated that without prenatal diagnosis, DS live-birth prevalence would have been 17.0 per 10,000 live births by 1995. Cultural factors influence demographic trends, birthing technologies, physician practices, and women’s decision-making regarding prenatal screening and diagnosis for DS

The Kalaallisut‐English Dictionary Project

Kalaallisut (West Greenlandic, iso‐639‐3 kal) is an Inuit language spoken in Greenland and is the official language of the country. In this presentation we discuss a collaborative project initiated by the Greenland Language Secretariat (Oqaasileriffik) to create a bilingual Kalaallisut‐English dictionary, aimed at two groups of users, Kalaallisut speakers who are learning English and English speakers learning Kalaallisut. We discuss the content and format of the dictionary, the underlying principles upon which it is being created, and the collaborative process itself. This collaborative project involves researchers from Greenland and the US. The dictionary, intended to include something in the order of 25,000‐35,000 entries, aims to provide the necessary information for both sets of users to both comprehend and produce both languages. The two languages are typologically distinct and there is limited correspondence between what counts as a word in each language. Kalaallisut is highly polysynthetic with very productive derivational and inflectional morphology, providing challenges for what constitutes a lexical entry versus which forms are one‐off creations by speakers. Language learners need information not only about word meaning, but also about “word” creation. By the same token, much of the grammatical information included in English words is encoded in Kalaallisut suffixes, providing challenges for Kalaallisut speakers learning English. The team began its work by establishing a core set of principles including: 1. The dictionary is based on the modern standard language, as currently spoken, with all entries approved by the Greenland Language Council (Oqaasiliortut). 2. The dictionary is usage‐driven. 3. The dictionary does not replace a reference grammar but provides an internal word grammar, i.e., it includes necessary and sufficient information for a user to generate correct word forms in both languages. 4. Irregular, unpredictable or otherwise not transparent forms need to be included. 5. The dictionary should include all necessary information for proper usage such as collocations, style and register information These principles are illustrated with sample entries from both languages. Entries are created through a collaborative process, but final approval of all material rests with Oqaasiliortut, the Language Council, which is part of the Greenland Self‐ Government. This particular project illustrates not only the importance of the concrete linguistic entries, but also the significance of the collaborative process of dictionary making, and the approval process, which is controlled by the local government