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Purpose: This study examined vocabulary profiles in young cochlear implant (CI) recipients and in children with normal hearing (NH) matched on receptive vocabulary size to improve our understanding of young CI recipients' acquisition of word categories (e.g., common nouns or closed-class words). Method: We compared receptive and expressive vocabulary profiles between young CI recipients (n = 48; mean age at activation = 15.61 months, SD = 4.20) and children with NH (n = 48). The two groups were matched on receptive vocabulary size as measured by the MacArthur-Bates Communicative Development Inventories (Fenson et al., 2006): Words and Gestures form. The CI group had, on average, 8.98 months of hearing experience. The mean chronological age at completing the MacArthur-Bates Communicative Development Inventories was 23.99 months (SD = 5.14) for the CI group and 13.72 months (SD = 1.50) for the NH group. Results: The CI group had a larger expressive vocabulary size than the receptive vocabulary size-matched NH group. The larger expressive vocabulary size was associated with the group difference in social words but not with common nouns. The analyses for predicate words and closed-class words included only children who produced the target categories. The CI group had a larger proportion of predicate words than the NH group, but no difference was found in closed-class words in expressive vocabulary. Conclusions: Differences found in expressive vocabulary profiles may be affected by spoken vocabulary size and their age. A further examination is warranted using language samples to understand the effect of language input on children's vocabulary profiles.

Background Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults. Methods We conducted a cross-sectional study of patients aged ≥18 years completing a family medicine clinic nonacute visit. Enzyme-linked immunosorbent assays were performed for AMPs. We identified associations between age and AMPs using unadjusted and multivariable linear regression models. Results Of the 308 subjects, 144 (46.8%) were ≥65 years of age. Comparing age ≥65 versus < 65 years, there were no significant differences in HNP 1-3 (p  = .371), HD5 (p  = .834), or LL-37 (p  = .348) levels. Values for hBD-2 were lower in older adults versus younger (p  < .001). In multivariable analyses, older males and females had significantly lower hBD-2 levels (p  < .001 and p  = .004). Models also showed urine leukocyte esterase was associated with increased levels of HNP 1-3 and HD5; hematuria with increased hBD-2; and urine cultures with contamination with increased HNP 1-3 and hBD-2. Conclusions Baseline urinary HNP 1-3, HD-5, and LL-37 did not vary with age. Older adults had lower baseline hBD-2. This finding has implications for the potential use of urinary AMPs as diagnostic markers and will facilitate further investigation into the role of innate immunity in UTI susceptibility in older adults. [ABSTRACT FROM AUTHOR]

Purpose: This study examined vocabulary profiles in young cochlear implant (Cl) recipients and in children with normal hearing (NH) matched on receptive vocabulary size to improve our understanding of young CI recipients' acquisition of word categories (e.g., common nouns or closed-class words). Method: We compared receptive and expressive vocabulary profiles between young CI recipients (n = 48; mean age at activation = 15.61 months, SD = 4.20) and children with NH (n = 48). The two groups were matched on receptive vocabulary size as measured by the MacArthur-Bates Communicative Development Inventories (Fenson et al., 2006): Words and Gestures form. The CI group had, on average, 8.98 months of hearing experience. The mean chronological age at completing the MacArthur-Bates Communicative Development Inventories was 23.99 months (SD = 5.14) for the CI group and 13.72 months (SD = 1.50) for the NH group. Results: The CI group had a larger expressive vocabulary size than the receptive vocabulary size-matched NH group. The larger expressive vocabulary size was associated with the group difference in social words but not with common nouns. The analyses for predicate words and closed-class words included only children who produced the target categories. The CI group had a larger proportion of predicate words than the NH group, but no difference was found in closed-class words in expressive vocabulary. Conclusions: Differences found in expressive vocabulary profiles may be affected by spoken vocabulary size and their age. A further examination is warranted using language samples to understand the effect of language input on children's vocabulary profiles., Our vocabularies are composed of a variety of word categories (e.g., nouns, verbs, adjectives), and the acquisition of words in these categories follows different developmental trajectories (Bates et al., 1994). [...]

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173. Plain language summary: Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m2 given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy. [ABSTRACT FROM AUTHOR]