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The study aims to investigate differences and similarities of two synonymous nouns, chance and opportunity. The sources of data were from the Corpus of Contemporary American English (COCA) and online dictionaries. The study applied both quantitative and qualitative methodology. Throughout the five text types of COCA (i.e. spoken, fiction, popular magazines, newspapers, and academic journals), opportunity was used most frequently in academic texts and was found least often in fiction. On the other hand, chance occurred least in the genre of academic texts and most often in the spoken genre. The claim that opportunity tends to be used more often in formal style than its near synonym was supported by a number of academic words in the list of its collocates. Although a wider range of meanings of chance reflects its polysemous status, chance and its collocates have fewer semantic preferences than those of opportunity. The findings also suggest that near-synonyms may behave differently in terms of collocation and semantic prosody although they share similar meanings.

Background: Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies., Methods: We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed., Results: Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88-109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73-168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41-75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31-146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting., Conclusions: Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects., Clinical Trials Registration: NCT02946190., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To evaluate outcomes in dual nucleoside reverse transcriptase inhibitor (NRTI) pretreated children after genotyping (GT)., Methods: We assessed CD4 and viral load (VL) in children three years after baseline GT at the time of dual NRTI failure. Baseline high grade resistance (HR) was defined as >or=4 nucleoside analogue mutations (NAMs)+/-Q151M or 69 insertion complex, and low grade resistance (LR) was defined as <4 NAMs. Genotypic susceptibility scores (GSS) were determined. The current selection of antiretrovirals (ARV) was based on physician judgment and ARV availability., Results: Seventy-two children were enrolled, with a mean age of 9.3 years; 61% were female. Baseline median CD4 was 18%, VL was 1.7 log(10) with HR 37.5%, LR 56.9% and no mutation (NR, no resistance) 5.6%. Sixty-five (90.3%) switched ARV: 46.2% non-nucleoside reverse transcriptase inhibitor (NNRTI), 30.8% protease inhibitor (PI), and 23.1% PI+NNRTI based highly active antiretroviral therapy (HAART). The choice of regimen did not differ based on baseline HR, LR, and NR. The median duration from dual NRTI therapy to HAART was 5.4 years (interquartile range (IQR) 4.0-6.9 years) and the mean (SD) duration of current HAART regimen was 1.51 (1.78) years; both were similar between ARV groups. Five children continued dual NRTI, two interrupted therapy. The GSS score was significantly higher in the PI group (3.1) vs. PI+NNRTI (2.5) vs. NNRTI (2.6) groups. Sixty-three percent of the HR group used PI or PI+NNRTI-based HAART compared to 41% of the LR group, p=not significant. At follow-up, median CD4 changes from baseline were +5% and VL -2.2 log(10) (p<0.001). VL <1.7 log(10) was seen in 59.3% of HR, 58.5% of LR, and 50.0% of NR groups (no significant difference). More children on PI (75%) and PI+NNRTI (80%) based HAART had VL <50 compared to NNRTI-based HAART (50%), p=0.003., Conclusion: PI-based regimens showed a higher rate of undetectable VL compared with NNRTI-based regimens. Having GT may not affect second-line treatment choices in developing countries, most likely due to late VL failure and limited availability of PIs.

Background: This study aimed to assess the long-term efficacy, safety and use of therapeutic drug monitoring (TDM) of a double-boosted protease inhibitor (PI) combination, saquinavir (SQV) and lopinavir/ritonavir (LPV/r), in Thai HIV type-1 (HIV-1)-infected children who had failed on reverse transcriptase inhibitors., Methods: In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4(+) T-cell count and percentage, viral load (VL; HIV-1 RNA), minimum plasma drug concentrations (C(min)) and drug safety laboratory evaluations were monitored. Virological failure was defined as having two consecutive VL measures >400 copies/ml after week 12. An intention-to-treat analysis was performed., Results: Baseline data were a median age of 9.3 years (interquartile range [IQR] 7.1-11.2), VL 4.8 log(10) copies/ml (IQR 4.5-5.1) and CD4(+) T-cell percentage 7% (IQR 3.0-9.5). CDC classifications were N=4%, A=14%, B=68% and C=14% of participants. Median CD4(+) T-cell percentage and CD4(+) T-cell count increase were 14% (IQR 7-19) and 558 cells/mm(3) (IQR 308-782), respectively (both P<0.001). Overall, 37 (74%) children achieved VL<50 copies/ml with significant differences between sites (90% versus 63%). Over 96 weeks, 10 patients had virological failure. Total cholesterol and high-density lipoprotein increased significantly over time, whereas the triglycerides and low-density lipoprotein did not. Approximately 50% of participants reported no change in body shape, and 33%, 43% and 39% reported fatter arms, face and abdomen, respectively. LPV and SQV C(min) were high and stable over time., Conclusions: Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close follow-up. On the basis of the TDM results, PI dose reduction in this population should be considered.