Targeted sequencing of ABCA7 identifies splicing, stop-gain and intronic risk variants for Alzheimer disease.

Several variants in the gene ABCA7 have been identified as potential causal variants for late-onset Alzheimer's disease (LOAD). In order to replicate these findings, and search for novel causal variants, we performed targeted sequencing of this gene in cohorts of non-Hispanic White (NHW) and African-American (AA) LOAD cases and controls. We sequenced the gene ABCA7 in 291 NHW LOAD cases and 103 controls. Variants were prioritized for rare, damaging variants and previously reported variants associated with LOAD, and were follow-up genotyped in 4076 NHW and 1157 AA cases and controls. We confirm three previously associated ABCA7 risk variants and extend two of these associations to other populations, an intronic variant in NHW (P=3.0×10-3) (originally reported in a Belgian population), and a splice variant originally associated in the Icelandic population, which was significantly associated in the NHW cohort (P=1.2×10-6) and nominally associated in the AA cohort (P=0.017). We also identify a 3'-UTR splice variant that segregates in four siblings of one family and is nominally associated with LOAD (P=0.040). Multiple variants in ABCA7 contribute to LOAD risk.

Sputum gram's stain in community-acquired pneumococcal pneumonia. A meta-analysis.

The usefulness of the sputum Gram's stain is controversial. This meta-analysis was designed to evaluate the sensitivity and specificity of the sputum Gram's stain in community-acquired pneumococcal pneumonia. Using a predetermined protocol, articles were discovered through a MEDLINE search (1966 to 1993) and the examination of bibliographies and were graded for quality by three blinded reviewers. Information on the reference standard, blinding, stain interpreter, control for antibiotic use, and definition of a positive test was collected. We found 12 articles containing 17 test characteristics to evaluate. The number of patients in each study ranged from 16 to 404. Sputum culture was the most common reference standard (10 of 17 estimations). Sensitivity ranged from 15% to 100% and specificity from 11% to 100%. Test characteristics varied markedly among studies and appeared related partly to the test interpreter. The sputum Gram's stain may yield misleading results in community-acquired pneumonia, as its sensitivity and specificity vary substantially in different settings. A practitioner electing to use the study should be well trained and use a specific definition for a positive test.