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Late-onset toxicities often occur in phase I trials investigating novel immunotherapy and molecular targeted therapies. For trials with cohort based designs (such as modified toxicity probability interval, Bayesian optimal interval, and i3+3), patients are often turned away since the current cohort are still being followed without definite dose-limiting toxicities, which results in prolonged trial duration and waste of patient resources. In this paper, we incorporate a probability-of-decision framework into the i3+3 design and allow real-time dosing inference when the next patient becomes available. Both follow-up time for the pending patients and time to dose-limiting toxicities for the observed patients are used in calculating the posterior probability of each possible dosing decision. An intensive simulation study is conducted to evaluate the operating characteristics of the newly proposed probability-of-decision-i3+3 design under various dosing scenarios and patient accrual settings. Results show that the probability-of-decision-i3+3 design achieves comparable safety and reliability performances but much shorter trial duration compared to the complete designs. [ABSTRACT FROM AUTHOR]

Background: Testosterone is used therapeutically in medical settings. Non-prescribed testosterone use is typically illegal, described as 'enhancement' or 'doping', and considered a problem. However, research has found that some non-prescribed testosterone use may be therapeutic (i.e. self-medication). Little is known about testosterone self-medication. It has been noted among individuals who use image and performance enhancing drugs (IPEDs), but never systematically explored.Approach: This paper describes the findings of a 4-year ethnographic study in online forums and social media groups frequented by people who use IPEDs. It focusses on 31 men who used enhancement doses of testosterone, but who described some of their testosterone use as 'testosterone replacement therapy' (TRT). In particular, it focuses on the 26 (84%) of these individuals who self-medicated TRT. Data was analysed thematically (using NVivo) in order to answer the question: 'how and why is testosterone self-medicated?'. Using Bacchi's (2016) problematization approach to policy analysis, this paper also asks, 'what happens to the 'problem' of non-prescribed testosterone use if such use is therapeutic?'.Findings: Self-medicated TRT was found to be very similar to TRT as practised in medical contexts. Self-medication was often practised because of an inability to access testosterone through health practitioners (who were either reluctant or unable to prescribe). However, some individuals were found to prefer self-medication because of price, ease of access, reliability of supply, and because health practitioners were perceived as lacking expertise regarding testosterone use.Conclusion: By documenting the therapeutic use of testosterone outside of medical settings, this paper calls into question previous conceptualisations of all illicit testosterone use as 'abuse', and the utility of the repair/enhancement dichotomy as a foundation for discussions of drug use. It suggests that in some cases the problem may not be non-prescribed testosterone use per se, but policies that prevent access to medical treatment. [ABSTRACT FROM AUTHOR]

This paper reports on a cross-language longitudinal study in which we extend previous research on the effects of maternal education on vocabulary growth in Spanish- and English-dominant children at three time points: 16 months, 22 months, and 30 months of age. This study addresses recent conflicting evidence regarding the role of maternal education in children's acquisition of Spanish. Participants were 62 English-dominant children, 47 Spanish-dominant children, and their mothers. Growth curve models were constructed separately for English and Spanish vocabulary. Strong growth rate reliability and effect sizes were evinced for vocabulary across samples. As expected, in English-dominant children, maternal education predicted English vocabulary and growth from 16 to 30 months of age. However, in Spanish-dominant children, there was no significant effect of maternal education on vocabulary or growth, although there was a descriptive advantage for children of college-educated mothers at 30 months of age. In conjunction with prior evidence, we conclude that the effect of maternal education on maternal input and child vocabulary does not generalize readily to children whose first language is Spanish. Our findings contribute to a literature that suggests that focusing on maternal beliefs, input, and the home literacy environment are more fruitful approaches in the study of children learning Spanish in the U.S. Further, the importance of maternal beliefs highlights the need to support parent investment in the quantity and quality of input in the home language. [ABSTRACT FROM AUTHOR]

Background: Vaccination rates for measles, mumps, and rubella (MMR) and diphtheria, tetanus, pertussis, and polio (Tdap-IPV) are not optimal among German adolescents. Education in combination with easy access to vaccination may be a promising approach to improve vaccination rates. The present paper describes a pilot study of a planned cluster randomized controlled trial (cRCT) in which we aim to improve MMR and Tdap-IPV vaccination rates together with knowledge and self-efficacy in a school setting.Methods: The study covered 863 students from 41 classes of four schools. The optimization and feasibility of access to schools, recruitment strategies, intervention, and assessment procedures were examined. The course and content of the educational unit were evaluated with a mixed-methods approach. A pre-post measurement design was tested for the vaccination rate in all schools. Additionally, at two schools, improvement in vaccination-related knowledge and perceived self-efficacy were measured by questionnaire pre-educational unit (n=287) and post-educational unit (n=293). The remaining two schools provided only postintervention data. Finally, we evaluated the psychometric properties (i.e., reliability, retest reliability, and change rates) of the questionnaire, applying Cronbach's alpha, factor analyses, generalized estimating equations and linear mixed models.Results: The findings of the pilot study indicated good feasibility. Of the total sample, 437 students (50.9%) brought their vaccination cards to school, 68 students received Tdap-IPV vaccinations, and 11 received MMR vaccinations. Out of six knowledge questions, on average, the students had M=2.84 (95% CI [2.69, 3.10]) correct answers before and M=4.45 (95% CI [4.26, 4.64]) after the class. Ranging from 1 to 4, the self-efficacy scale changed by 0.3 points (p <.001); Cronbach's alpha was 0.67 and 0.76 pre- and post-educational unit, respectively, and a one-factor solution was found. Content analysis of the five semistructured group interviews (n=12, 58.3% female) showed that all students found the length of the intervention to be appropriate. The teaching methods, including interactive and social media components, were perceived as very good.Conclusions: A school-based educational and on-site vaccination intervention appears to be feasible in terms of procedures and the adequacy of the instruments for the adolescent target group.Trial Registration: ISRCTN, ISRCTN18026662 . Pilot study for main trial registered 8 December 2017. [ABSTRACT FROM AUTHOR]