L2 competence in Chinese correlative connectives: A case of discontinuous discursive formulaic sequences

This study explored second language (L2) competence in discontinuous discursive formulaic sequences, namely Chinese correlative connectives (CCCs; e.g. yīnwèi . . . suǒyǐ ‘because . . . so’), in relation to the determinants of formulaic sequence acquisition by scrutinizing L2 Chinese learners’ performance on two controlled tasks. Mixed-effects modeling showed that frequency exerted both positive and negative effects on the task performance of L2 learners on CCCs. Contingency (i.e. the co-occurrence of two constituent connectives) posed a tremendous challenge to the use of obligatory CCCs by L2 learners. In contrast, semantic transparency and first language congruency had a positive effect. The effects of these determinants on L2 performance were qualified by their interactions in different categories of CCCs. The results also indicated that learners were sensitive to frequency and contingency determinants at both construction and constituent word levels. This study enriches our understanding of L2 competence in formulaic language and provides unique insights into L2 learners’ knowledge of CCCs.

Heritage Tagalog Phonology and a Variationist Framework of Language Contact

Heritage language variation and change provides an opportunity to examine the interplay of contact-induced and language-internal effects while extending the variationist framework beyond monolingual speakers and majority languages. Using data from the Heritage Language Variation and Change in Toronto Project, we illustrate this with a case study of Tagalog (r), which varies between tap, trill, and approximant variants. Nearly 3000 tokens of (r)-containing words were extracted from a corpus of spontaneous speech of 23 heritage speakers in Toronto and 9 homeland speakers in Manila. Intergenerational and intergroup analyses were conducted using mixed-effects modeling. Results showed greater use of the approximant among second-generation (GEN2) heritage speakers and those that self-report using English more. In addition, the distributional patterns remain robust and the approximant appears in more contexts. We argue that these patterns reflect an interplay between internal and external processes of change. We situate these findings within a framework for distinguishing sources of variation in heritage languages: internal change, identity marking and transfer from the dominant language.

Identifying Practices to Promote Inpatient Adolescent and Influenza Vaccine Delivery

OBJECTIVES Many hospitalized children are underimmunized. We assessed the association between hospital immunization practices and tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal, human papillomavirus (HPV), and influenza vaccine delivery. METHODS An electronic survey regarding hospital vaccine delivery practices was distributed via the Pediatric Health Information System (PHIS) and Pediatric Research in Inpatient Settings networks to PHIS hospitals. Number of vaccines delivered and total discharges in 2018 were obtained from the PHIS database to determine hospital vaccine delivery rates; patients 11 to 18 years old (adolescent vaccines) and 6 months to 18 years old (influenza vaccine) were included. Vaccine delivery rates were risk adjusted by using generalized linear mixed-effects modeling and compared with survey responses to determine associations between the number or presence of specific practices and vaccine delivery. Adjusted HPV and meningococcal vaccine delivery rates could not be calculated because of low delivery. RESULTS Twenty-nine hospitals completed a survey (57%). 152 499 and 423 046 patient encounters were included for the adolescent and influenza vaccines, respectively. Unadjusted inpatient vaccine delivery rates varied. After adjustment, the number of practices was associated only with influenza vaccine delivery (P = .02). Visual prompts (P = .02), nurse or pharmacist ordering (P = .003), and quality improvement projects (P = .048) were associated with increased influenza vaccine delivery; nurse or pharmacist ordering had the greatest impact. No practices were associated with Tdap vaccine delivery. CONCLUSIONS The number and presence of specific hospital practices may impact influenza vaccine delivery. Further research is needed to identify strategies to augment inpatient adolescent immunization.

EMOTION-LADEN TEXTS AND WORDS

This study takes a mixed-methods approach to explore the influence of emotion-laden (positive vs. negative vs. neutral) texts and words on vocabulary learning for Spanish heritage and foreign language learners. Participants (N = 121) were tasked with learning emotion-laden pseudowords embedded in three emotion-laden texts centered around themes of bilingualism, immigration, and identity. Form recognition, translation, and multiple-choice tests were designed to measure vocabulary recall and retention. Results from a mixed-effects modeling analysis showed that the neutral and negative emotion-laden texts predicted better vocabulary learning outcomes than the positive text for both HLLs and FLLs and that neutral words were learned best by all learners. Qualitative findings from open-ended questionnaires suggest emotional arousal as another influential affective factor in vocabulary learning for learners of diverse sociolinguistic backgrounds. Directions for future emotions research in SLA and pedagogical implications of socially relevant, emotion-laden material for vocabulary learning are discussed.

Detraining Slows and Maintenance Training Over 6 Years Halts Parkinsonian Symptoms-Progression

Introduction: There are scant data to demonstrate that the long-term non-pharmaceutical interventions can slow the progression of motor and non-motor symptoms and lower drug dose in Parkinson's disease (PD).Methods: After randomization, the Exercise-only (E, n = 19) group completed an initial 3-week-long, 15-session supervised, high-intensity sensorimotor agility exercise program designed to improve the postural stability. The Exercise + Maintenance (E + M, n = 22) group completed the 3-week program and continued the same program three times per week for 6 years. The no exercise and no maintenance control (C, n = 26) group continued habitual living. In each patient, 11 outcomes were measured before and after the 3-week initial exercise program and then, at 3, 6, 12, 18, 24, 36, 48, 60, and 72 months.Results: The longitudinal linear mixed effects modeling of each variable was fitted with maximum likelihood estimation and adjusted for baseline and covariates. The exercise program strongly improved the primary outcome, Motor Experiences of Daily Living, by ~7 points and all secondary outcomes [body mass index (BMI), disease and no disease-specific quality of life, depression, mobility, and standing balance]. In E group, the detraining effects lasted up to 12 months. E+M group further improved the initial exercise-induced gains up to 3 months and the gains were sustained until year 6. In C group, the symptoms worsened steadily. By year 6, levodopa (L-dopa) equivalents increased in all the groups but least in E + M group.Conclusion: A short-term, high-intensity sensorimotor agility exercise program improved the PD symptoms up to a year during detraining but the subsequent 6-year maintenance program was needed to further increase or sustain the initial improvements in the symptoms, quality of life, and drug dose.

Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children

Intermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84–99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children.

PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci

Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95%CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.

The Use of Cannabinoids for Insomnia in Daily Life: Naturalistic Study

Background Insomnia is a prevalent condition that presents itself at both the symptom and diagnostic levels. Although insomnia is one of the main reasons individuals seek medicinal cannabis, little is known about the profile of cannabinoid use or the perceived benefit of the use of cannabinoids in daily life. Objective We conducted a retrospective study of medicinal cannabis users to investigate the use profile and perceived efficacy of cannabinoids for the management of insomnia. Methods Data were collected using the Strainprint app, which allows medicinal cannabis users to log conditions and symptoms, track cannabis use, and monitor symptom severity pre- and postcannabis use. Our analyses examined 991 medicinal cannabis users with insomnia across 24,189 tracked cannabis use sessions. Sessions were analyzed, and both descriptive statistics and linear mixed-effects modeling were completed to examine use patterns and perceived efficacy. Results Overall, cannabinoids were perceived to be efficacious across all genders and ages, and no significant differences were found among product forms, ingestion methods, or gender groups. Although all strain categories were perceived as efficacious, predominant indica strains were found to reduce insomnia symptomology more than cannabidiol (CBD) strains (estimated mean difference 0.59, SE 0.11; 95% CI 0.36-0.81; adjusted P<.001) and predominant sativa strains (estimated mean difference 0.74, SE 0.16; 95% CI 0.43-1.06; adjusted P<.001). Indica hybrid strains also presented a greater reduction in insomnia symptomology than CBD strains (mean difference 0.52, SE 0.12; 95% CI 0.29-0.74; adjusted P<.001) and predominant sativa strains (mean difference 0.67, SE 0.16; 95% CI 0.34-1.00; adjusted P=.002). Conclusions Medicinal cannabis users perceive a significant improvement in insomnia with cannabinoid use, and this study suggests a possible advantage with the use of predominant indica strains compared with predominant sativa strains and exclusively CBD in this population. This study emphasizes the need for randomized placebo-controlled trials assessing the efficacy and safety profile of cannabinoids for the treatment of insomnia.

Pathogenesis of obstructive sleep apnea in people living with HIV

Obstructive sleep apnea (OSA) is highly prevalent in people living with HIV (PLWH), and might contribute to frequently reported symptoms and co-morbidities. Traditional risk factors for OSA are often absent in PLWH, suggesting that HIV or HIV medications might predispose to OSA. Therefore, we measured the anatomical and non-anatomical traits important for OSA pathogenesis in those with and without HIV. We recruited virally-suppressed PLWH who had been previously diagnosed with OSA (PLWH+OSA) adherent to positive airway pressure (PAP) therapy, along with age, gender and body mass index (BMI) matched OSA controls. All participants underwent a baseline polysomnogram to assess OSA severity, and a second overnight research sleep study during which the airway pressure was adjusted slowly or rapidly to measure the OSA traits. Seventeen PLWH+OSA and 17 OSA control participants were studied (median age 58 IQR[54, 65] years, BMI 30.7 [28.4, 31,8] kg/m2, apnea-hypopnea index 46 [24, 74]/h. The groups were similar, although PLWH+OSA demonstrated greater sleepiness (despite PAP) and worse sleep efficiency on baseline polysomnography. On physiological testing during sleep, there were no statistically significant differences in OSA traits (including Veupnea, Varousal, Vpassive, Vactive, and loop gain) between PLWH+OSA and OSA controls, using mixed-effects modeling to account for age, gender, and BMI, and incorporating each repeated measurement (range 72-334 measures/trait). Our data suggest that well treated HIV does not substantially impact the pathogenesis of OSA. Given similar underlying physiology, existing available therapeutic approaches are likely to be adequate to manage OSA in PLWH, which might improve symptoms and co-morbidities.