Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement.

Additionally, CHO intake in U18s was lower (P<0.05) at breakfast, dinner and snacks 56 when compared with both squads but no differences were apparent at lunch. 57Furthermore, the U15/16s reported lower relative daily protein intake than the 58 U13/14s and U18s (1.6±0.3 vs. 2.2±0.5, 2.0±0.3 g·kg -1 ). A skewed distribution 59 (P<0.05) of daily protein intake was observed in all squads, with a hierarchical order 60 of dinner (~0.6 g·kg -1 ) > lunch (~0.5 g·kg -1 ) > breakfast (~0.3 g·kg -1 ). We conclude 61 elite youth soccer players do not meet current CHO guidelines. Although daily protein 62 targets are achieved, we report a skewed daily distribution in all ages such that 63 dinner>lunch>breakfast. Our data suggest that dietary advice for elite youth players 64 should focus on both total daily macronutrient intake and optimal daily distribution 65 patterns. al., 2015). These studies have typically been limited to reports of total daily energy 80and macronutrient intake, often concluding that elite youth soccer players habitually 81 don't meet their energy requirements (Boisseau et al. 2002; LeBlanc et al., 2002; Ruiz 82 et al., 2005;Russell and Pennock, 2011; Briggs et al., 2015). 83In addition to the quantification of daily energy and macronutrient intake, it is 84 important to consider timing of intake in relation to training sessions (Burke, 2010; 85 Mori, 2014), main meals (Garaulet and Gomez-Abellan, 2014; Johnston, 2014) and 86 sleep (Lane et al., 2015). Whilst this is most well documented for carbohydrate 87 (CHO) intake in order to fuel training and matches (Goedecke et al., 2013; 88 Jeukendrup, 2014) and promote glycogen re-synthesis (Zehnder et al., 2001; 89 Gunnarsson et al., 2013), recent data suggests that the daily distribution of protein 90 intake is critical for optimizing components of training adaptations such as muscle 91 protein synthesis (MPS) (Areta et al., 2013; Mamerow et al., 2014). Recent data has 92 highlighted the importance of quantity and timing of protein intake in elite youth 93 soccer players. Milsom et al. (2015) demonstrated that such populations typically 94 Therefore, the aims of the present study were two-fold: 1) to quantify the total daily 101 energy and macronutrient intakes of elite youth UK academy players of different ages 102 (U13/14, U15/16 and U18 playing squads) and 2) to quantify the daily distribution of 103 energy and macronutrient intake. In accordance with the higher absolute body masses 104 and training loads of the U18 squads (Wrigley et al., 2012), we hypothesised that this 105 squad would report higher absolute daily energy and macronutrient intakes in 106 comparison to the U13/14s and U15/16s. Furthermore, based on the habitual eating 107 patterns of both athletic and non-athletic populations (Mamerow et al., 2014), we 108 hypothesised that all squads would report an uneven daily distribution of 109 macronutrient intakes, particularly for daily protein intake. 110 Methodology 111 Participants 112Elite youth soccer players were recruited ...

The objective of these studies was to characterize the macrophage mannose receptor binding and pharmacological properties of carbohydrate remodeled human placental-derived and recombinant β-glucocerebrosidase (pGCR and rGCR, respectively). These are similar but not identical molecules that were developed as enzyme replacement therapies for Gaucher disease. Both undergo oligosaccharide remodeling during purification to expose terminal mannose sugar residues. Competitive binding data indicated carbohydrate remodeling improved targeting to mannose receptors over native enzyme by two orders of magnitude. Mannose receptor dissociation constants (Kd) for pGCR and rGCR were each 13 nmol/L. At 37°C, 95% of the total macrophage binding was mannose receptor specific. In vivo, pGCR and rGCR were cleared from circulation by a saturable pathway. The serum half-life (t1/2) was 3 minutes when less than saturable amounts were injected intravenously (IV) into mice. Twenty minutes postdose, β-glucocerebrosidase activity increased over endogenous levels in all tissues examined. Fifty percent of the injected activity was recovered. Ninety-five percent of recovered activity was in the liver. Parenchymal cells (PC), Kupffer cells (KC), and liver endothelium cells (LEC) were responsible for 75%, 22%, and 3%, respectively, of the hepatocellular uptake of rGCR and for 76%, 11%, and 12%, respectively, of the hepatocellular uptake of pGCR. Both molecules had poor stability in LEC and relatively long terminal half-lives in PC (t1/2 = 2 days) and KC (t1/2 = 3 days).

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