The causes of age-related differences in lower-extremity joint moments and powers are unknown. The purpose of this study was to determine the effects of highly physically active older adults walking with (1) a step length similar to young adults and (2) an upright trunk posture, on hip and ankle joint kinetics. The authors hypothesized that, compared with their self-selected walking mechanics, older adults would exhibit decreased hip kinetics and increased ankle kinetics when prescribed a young adult step length, and would exhibit decreased hip extension moments when maintaining an upright trunk posture during walking. A total of 12 active older adults (67 [5] y) and 13 active young adults (21 [3] y) walked at 1.3 m/s. The older adults also walked at 1.3 m/s with step lengths prescribed from height-matched young adults and, in a separate condition, walked with an upright trunk. The older adults did not display larger ankle kinetics or smaller hip kinetics in either condition compared to walking with a self-selected step length. These findings indicate that step length and trunk position do not primarily contribute to age-related differences in kinetics in highly active older adults and should serve as a starting point for investigating alternative explanations.BACKGROUND Physical exercise plays an important role in metabolic health, especially in the insulin-like growth factor-1 (IGF-1) system. The objective of this study was to perform a systematic review and meta-analysis to evaluate the effects of a single endurance and resistance exercise session on IGF-1 serum. METHODS The systematic review was performed in SPORTDiscus, MEDLINE, PubMed, and Google Scholar databases. All analyses are based on random-effect models. The study identified 249 records of which 21 were included. RESULTS There was an effect of endurance exercise on total IGF-1 (P = .01), but not for free IGF-1 (P = .36). Resistance exercise similarly only affected total IGF-1 (P = .003) and not free IGF-1 (P = .37). The effect size indicated that total IGF-1 is more affected (ES = 0.81) by endurance than by resistance exercise (ES = 0.46). The present study showed that IGF-1 serum concentrations are altered by exercise type, but in conditions which are not well-defined. CONCLUSIONS The systematic review and meta-analysis suggest that there is no determinant in serum IGF-1 changes for the exercise load characteristic. Therefore, physical exercise may be an alternative treatment to control changes in IGF-1 metabolism and blood concentration.BACKGROUND As progress continues in oncology drug development, this study aimed to examine whether the previously established association between drug dose and efficacy in the era of cytotoxic therapies remains true in today's phase I dose-escalation oncology trials. METHODS A systematic review of early-phase dose-finding trials of single-agent oncology drugs from 2015 to 2018 was conducted to examine the relationship between drug dose and objective responses. Cancer-specific trials were included if they determined maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Data related to the study drug, study design, treatment response, cancer type, dose levels, MTD, and RP2D were all collected. Dose level was categorized into 4 categories (≤40%, 41%-80%, 81%-120%, and >120% of the RP2D) and was further analyzed by class of drug. RESULTS A total of 175 phase I studies were identified, with a total of 7,330 patients showing a median response rate of 5% (range, 0%-83%) across trials. https://www.selleckchem.com/products/incb084550.html A total of 93 trials with 2,506 participants had response data corresponding to drug dose level. In this subset, the median response rate was 5% (range, 0%-83%) across trials. Across all participants in this subset, the response rate was 12% (57 of 491) among those in the dose range of ≤40% of RP2D, 17% (95 of 562) among those in 41% to 80% of RP2D, 23% (272 of 1,206) among those in 81% to 120% of RP2D, and 29% (71 of 247) among those in >120% of RP2D (P less then .001). The response rate at ≤40% of RP2D for targeted antibody was 5%, 4% for cellular therapy, 19% for immunotherapy, and 21% for small-molecule targeted inhibitors. CONCLUSIONS Whereas our study of published phase I trials continued to show a low response rate consistent with earlier studies, the relationship between response and dose does not always peak at 81% to 120% of RP2D anymore, likely due to the use of novel immunotherapy and targeted agents with distinct efficacy and toxicity patterns.BACKGROUND This study sought to describe how high- versus low-frequency surveillance imaging practices among providers at Memorial Sloan Kettering Cancer Center (MSKCC) impact overall survival (OS) and time to recurrence of patients with advanced epithelial ovarian cancer in first remission. METHODS The study cohort included patients with stage II-IV high-grade epithelial ovarian cancer diagnosed in January 2001 through January 2017 who experienced recurrence after initial platinum-based chemotherapy. To determine usual imaging practices for providers at MSKCC, median frequency of CT or MRI of the abdomen/pelvis was calculated among patients with a long-term remission (defined as at least 1 year) treated by each provider. Cox proportional hazards models were used to examine differences in OS and time to recurrence among patients treated by providers with high versus low imaging frequency practices, with additional subgroup analysis among patients with elevated CA-125 levels >35 U/mL at diagnosis. Chi-square tests were used to examine differences in the proportion of patients who enrolled in clinical trials or underwent secondary cytoreductive surgery (SCS) by imaging frequency. RESULTS A total of 543 patients were treated by providers with high imaging frequency (>1 scan every 12 months) and 141 were treated by providers with low imaging frequency (≤1 scan every 12 months). Time to recurrence was shorter among patients treated by providers with high versus low imaging frequency (18.0 vs 19.2 months; hazard ratio, 1.33; P=.003). Results were similar when restricted to patients with elevated CA-125 levels at diagnosis. There was no significant difference in OS, clinical trial enrollment, or SCS by imaging practice. CONCLUSIONS Within the limitations of this retrospective analysis, patients with advanced ovarian cancer treated by high-frequency-imaging providers had earlier detection of recurrence. Future analyses in a larger population are warranted to elucidate the risks versus benefits of surveillance imaging.