Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

NI margins have to be chosen appropriately to control the risk of degradation of treatment effects in non-inferiority (NI) trials. We aimed to study whether the current choice of NI margins protects sufficiently against a degradation of treatment effect on an average.', 'NI trials reflecting current practice were assembled and for each trial, the NI margin was translated into a likelihood of degradation. The likelihood of degradation was calculated as the conditional probability of a treatment being harmful given that it is declared non-inferior in the trial, using simulation. Its distribution among the NI trials was then studied to assess the potential risk of degradation.', "The median (lower/upper quartile) NI margin among 112 binary outcome NI trials corresponded to an odds ratio of 0.57(0.45, 0.66), while among 38 NI trials with continuous outcome, to a Cohen's d of -0.42(-0.54, -0.31) and a hazard ratio of 0.82(0.73, 0.86) among 24 survival outcome NI trials. Overall, the median likelihood of degradation was 56% (45%, 62%).
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A limited amount of literature suggests that plasma leptin concentrations are reduced with habitual physical activity in men and non-pregnant women. We investigated the relationship between maternal physical activity and plasma leptin during early pregnancy.', 'The study population included 879 normotensive, non-diabetic pregnant women who reported physical activity type, frequency, and duration in early pregnancy. Plasma leptin, measured in blood samples collected <16 weeks gestation, were determined using enzyme immunoassays. Weekly duration (h/week) and energy expended on recreational physical activity [metabolic equivalent score (MET)-h/week] were categorized by tertiles among active women. Physical activity intensity was categorized as none, moderate (<6 MET) and vigorous (> or =6 MET). Differences in leptin concentrations across categories were estimated using linear regression procedures.', 'Mean leptin was 5.8 ng/ml lower among active versus inactive women (P=0.001). Mean leptin was lower among women in the highest levels (>12.8 h/week) of time performing physical activity (-8.1 ng/ml, P<0.001) and energy expenditure (>70.4 MET-h/week) (-8.3 ng/ml, P=0.001) compared with inactive women. Leptin was inversely associated with the intensity of physical activity.
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Heterotopic ossification (HO) may occur after musculoskeletal trauma, traumatic brain injury, and total joint arthroplasty. As such, HO is a compelling clinical concern in both military and civilian medicine. A possible etiology of HO involves dysregulated signals in the bone morphogenetic protein osteogenic cascade. Contemporary treatment options for HO (ie, nonsteroidal antiinflammatory drugs and radiation therapy) have adverse effects associated with their use and are not biologically engineered to abrogate the molecular mechanisms that govern osteogenic differentiation.', 'We hypothesized that (1) nanogel-mediated short interfering RNA (siRNA) delivery against Runt-related transcription factor 2 (Runx2) and osterix (Osx) genes will decrease messenger RNA expression; (2) inhibit activity of the osteogenic marker alkaline phosphatase (ALP); and (3) inhibit hydroxyapatite (HA) deposition in osteoblast cell cultures.', 'Nanogel nanostructured polymers delivered siRNA in 48-hour treatment cycles against master osteogenic regulators, Runx2 and Osx, in murine calvarial preosteoblasts (MC3T3-E1.4) stimulated for osteogenic differentiation by recombinant human bone morphogenetic protein (rhBMP-2). The efficacy of RNA interference (RNAi) therapeutics was determined by quantitation of messenger RNA knockdown (by quantitative reverse transcription-polymerase chain reaction), downstream protein knockdown (determined ALP enzymatic activity assay), and HA deposition (determined by OsteoImage™ assay).', 'Gene expression assays demonstrated that nanogel-based RNAi treatments at 1:1 and 5:1 nanogel:short interfering RNA weight ratios reduced Runx2 expression by 48.59%\xa0±\xa019.53% (p\xa0<\xa00.001) and 43.22%\xa0±\xa018.01% (both p\xa0<\xa00.001). The same 1:1 and 5:1 treatments against both Runx2 and Osx reduced expression of Osx by 51.65%\xa0±\xa010.85% and 47.65%\xa0±\xa09.80% (both p\xa0<\xa00.001). Moreover, repeated 48-hour RNAi treatment cycles against Runx2 and Osx rhBMP-2 administration reduced ALP activity after 4 and 7\xa0days. ALP reductions after 4\xa0days in culture by nanogel 5:1 and 10:1 RNAi treatments were 32.4%\xa0±\xa012.0% and 33.6%\xa0±\xa013.8% (both p\xa0<\xa00.001). After 7\xa0days in culture, nanogel 1:1 and 5:1 RNAi treatments produced 35.9%\xa0±\xa014.0% and 47.7%\xa0±\xa03.2% reductions in ALP activity. Osteoblast mineralization data after 21\xa0days suggested that nanogel 1:1, 5:1, and 10:1 RNAi treatments decreased mineralization (ie, HA deposition) from cultures treated only with rhBMP-2 (p\xa0<\xa00.001). However, despite RNAi attack on Runx2 and Osx, HA deposition levels remained greater than non-rhBMP-2-treated cell cultures.

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