Patients with M. abscessus pulmonary disease who are treated with multidrug antibiotic therapy and surgery or antibiotic therapy alone had similar clinical outcomes. However, surgical resection, in addition to antibiotics, may offer a prolonged microbiologic response.

Rationale: The characterization of young adults who develop lateonset diseases may augment the detection of novel genes and promote new pathogenic insights. Methods: We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n ¼ 70, age , 55 yr, FEV 1 , 50% predicted) were compared with older subjects with COPD (n ¼ 306, age . 64 yr, FEV 1 , 50% predicted). Measurements and Main Results: Subjects with severe, early-onset COPD were predominantly females (66%), P ¼ 0.0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P , 0.0001. Other risk factors included current smoking (56 vs. 17%, P , 0.0001) and self-report of asthma (39 vs. 25%, P ¼ 0.008). Maternal smoking (70 vs. 44%, P ¼ 0.0001) and maternal COPD (23 vs. 12%, P ¼ 0.03) were reported more commonly in subjects with earlyonset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3-24; P ¼ 0.0007); maternal COPD, OR, 4.7 (95% CI, 1.3-17; P ¼ 0.02); female sex, OR, 3.1 (95% CI, 1.1-8.7; P ¼ 0.03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96-1.0; P ¼ 0.03). Conclusions: These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions.Keywords: chronic obstructive pulmonary disease; female; African Americans Chronic obstructive pulmonary disease (COPD) is typically a disease that presents in late adulthood, often associated with cigarette smoking (1, 2). Although the prevalence of COPD has been changing, COPD is more prevalent in individuals older than 65 years of age (3). Previously considered a disease affecting primarily males, the prevalence of COPD in women and the number of women dying from COPD have increased (4). Maturity-onset diseases are complex; they may have multiple causes with contributions from environmental exposures, comorbidities, age-related degenerative changes, and genetic factors. Diseases occurring at an earlier age than traditionally expected may result from the interaction of inherited factors and environmental exposures.In 1998, a family-based cohort composed of 44 probands with severe, early-onset COPD recruited from specialized programs in lung transplantation, lung volume reduction surgery, and local pulmonary clinics and 249 first-or second-degree relatives was reported (5). Eligibility criteria for inclusion as a proband included the following: (1) age not greater than 52 years, (2) the absence of severe a 1 -antitrypsin deficiency, and (3) FEV 1 less than 40% predicted. This first report was notable for the high percentage of female probands (80%). However, whether earlyonset COPD is a specific phenotype and whether it is a ...

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Hemophilia A is an X-linked bleeding disorder caused by mutations in the gene encoding the factor VIII (FVIII) coagulation protein. Bleeding episodes in patients are reduced by prophylactic therapy or treated acutely using recombinant or plasma-derived FVIII. We have made an adeno-associated virus 5 vector containing a B domain-deleted (BDD) FVIII gene (BMN 270) with a liver-specific promoter. BMN 270 injected into hemophilic mice resulted in a dose-dependent expression of BDD FVIII protein and a corresponding correction of bleeding time and blood loss. At the highest dose tested, complete correction was achieved. Similar corrections in bleeding were observed at approximately the same plasma levels of FVIII protein produced either endogenously by BMN 270 or following exogenous administration of recombinant BDD FVIII. No evidence of liver dysfunction or hepatocyte endoplasmic reticulum stress was observed. Comparable doses in primates produced similar levels of circulating FVIII. These preclinical data support evaluation of BMN 270 in hemophilia A patients.

Non-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.

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CuInS 2 quantum dots (QDs) are promising alternatives for user-and environment-friendly light-emitting diode (LED) applications, but the capping of electrically insulating ligands on QDs limits the device charge injection efficiency and results in poor LED performance. To solve the problem, in this work, we demonstrate the facile synthesis of Cu−In−S/ZnS (CIS/ZnS) core/shell QDs employing 1dodecanethiol (DT) as the single ligand. The capping of QDs solely by DT not only enhances the colloidal stability of the QD ink by avoiding proton transfer between different kinds of ligands but also improves the electrical property of the QD films. By controlling the molar feed ratio of cations, the photoluminescence emission peak of the CIS/ZnS QDs is tunable from 530 to 710 nm. Because the QD surface chemistry is optimized, it becomes facile to perform QD surface modification for LED application. A QD LED prototype is fabricated using CIS/ZnS QDs as the emissive layer, which exhibits a maximum luminance of 4490 cd m −2 and a peak external quantum efficiency of 7.8%, boosting the best performance of CIS QD-based LEDs.