Study 1 demonstrated that as individuals' promotion-related ideal strength increases, performance on an anagram task is greater for a monetary task incentive framed in terms of gains and nongains (i.e., promotion framed) than one framed in terms of losses and nonlosses (i.e., prevention framed), whereas the reverse is true as individuals' prevention-related ought strength increases. Study 2 further demonstrated that with promotion-framed task incentives, individuals' ideal' strength increases motivation for promotion-related goal attainment means (gaining points), whereas with prevention-framed task incentives, individuals' ought strength increases motivation for prevention-related means (avoiding losing points). These results suggest that motivation and performance are greater when the regulatory focus of task incentives and means match (vs. mismatch) the chronic regulatory focus of the performers.

SummaryBackgroundLung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.MethodsWe did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867.FindingsBetween June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups.InterpretationMonthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials.FundingMedical Research Council/National Institute for Health Research Efficacy and Mechanism Evaluation Programme.

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In 3 experiments, the authors investigated how strategic inclinations associated with promotion versus prevention orientations-that is, eager approach versus vigilant avoidance, respectively-affect the use of language. It is hypothesized that eager promotion strategies used to attain desired end states entail using more abstract language than used with vigilant prevention strategies. This is shown to hold for experimentally induced relationship goals (Experiment 1) and communication goals (Experiment 2). In the 3rd experiment, the authors examined the impact of abstractly and concretely worded messages upon the behavioral intentions of chronically prevention-and promotion-oriented individuals and found support for the hypothesis that behavioral intentions to engage in specific activities are stronger when there is a fit between message wording and chronic orientation than when there is no fit. The broader implications of these findings are discussed.

We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, the effect was modest, and more potent gene transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase protein (HN)-pseudotyped lentiviral vectors are more efficient for lung gene transfer than non-viral vectors in preclinical models. In preparation for a first-in-man CF trial using the lentiviral vector, we have undertaken key translational preclinical studies. Regulatory-compliant vectors carrying a range of promoter/enhancer elements were assessed in mice and human air–liquid interface (ALI) cultures to select the lead candidate; cystic fibrosis transmembrane conductance receptor (CFTR) expression and function were assessed in CF models using this lead candidate vector. Toxicity was assessed and ‘benchmarked’ against the leading non-viral formulation recently used in a Phase IIb clinical trial. Integration site profiles were mapped and transduction efficiency determined to inform clinical trial dose-ranging. The impact of pre-existing and acquired immunity against the vector and vector stability in several clinically relevant delivery devices was assessed. A hybrid promoter hybrid cytosine guanine dinucleotide (CpG)- free CMV enhancer/elongation factor 1 alpha promoter (hCEF) consisting of the elongation factor 1α promoter and the cytomegalovirus enhancer was most efficacious in both murine lungs and human ALI cultures (both at least 2-log orders above background). The efficacy (at least 14% of airway cells transduced), toxicity and integration site profile supports further progression towards clinical trial and pre-existing and acquired immune responses do not interfere with vector efficacy. The lead rSIV.F/HN candidate expresses functional CFTR and the vector retains 90–100% transduction efficiency in clinically relevant delivery devices. The data support the progression of the F/HN-pseudotyped lentiviral vector into a first-in-man CF trial in 2017.

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Objective Over 15 million adolescents, many at high risk for pregnancy, use emergency departments (ED) in the United States annually, but little is known regarding reasons for failure to use contraceptives in this population. The purpose of this study was to identify the barriers to and enablers of contraceptive use among adolescent females using the ED and determine their interest in an ED-based pregnancy prevention intervention. Study Design We conducted semi-structured, open-ended interviews with females in an urban ED. Eligible females were 14-19 years old, sexually active, presenting for reproductive health complaints, and at risk for pregnancy, defined as non-use of effective (per the World Health Organization) contraception. Interviews were recorded, transcribed, and coded based on thematic analysis. Enrollment continued until no new themes emerged. A modified Health Belief Model guided the organization of the data. Results Participants (n=14) were predominantly Hispanic (93%), insured (93%), and in a sexual relationship (86%). The primary barrier to contraceptive use was perceived health risk, including effects on menstruation, weight, and future fertility. Other barriers consisted of mistrust in contraceptives, ambivalent pregnancy intentions, uncertainty about the future, partner's desire for pregnancy, and limited access to contraceptives. Enablers of past contraceptive use included the presence of a school-based health clinic and clear plans for the future. All participants were receptive to ED-based pregnancy prevention interventions. Conclusions The identified barriers and enablers influencing hormonal contraceptive use can be used to inform the design of future ED-based adolescent pregnancy prevention interventions.

Actions require two essential functions: assessment and locomotion. Assessment determines one's goals and selects the means. Locomotion translates these into concrete behavior. In past work, assessment and locomotion have been portrayed as co-ordinated and interdependent, or associated with different action phases. In contrast, we review recent theorizing and research that depict assessment and locomotion as autonomous and complementary. Recent evidence supports this conception for the behavior of individuals, groups, organizations, and cultures in reference to actions at different levels of analysis.Actions are among life's most basic phenomena. They form the very essence of human experience. From dawn to dusk, we move from one activity to another in an uninterrupted sequence. Brushing our teeth, getting dressed, driving to work, running errands, having lunch, getting home, and relaxing are all doings that make up the days of our lives.Scientists and laypersons agree that actions are purposive. They aim at particular ends, achieved by specific means. Recent research has made important forays into understanding actions, and has afforded new insights into their fundamental ingredients. These ingredients comprise the functions of assessment and locomotion. Assessment consists of selecting the goals and choosing the appropriate means. It requires gathering the relevant evidence and making the appropriate decisions. Locomotion involves carrying out the suggested activities and moving forward toward one's objectives.