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To increase the efficiency and effectiveness of clinical research studies, cerebral palsy (CP) specific Common Data Elements (CDEs) were developed through a partnership between the National Institute of Neurological Disorders and Stroke (NINDS) and the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM). International experts reviewed existing NINDS CDEs and tools used in studies of children and young people with CP. CDEs were compiled, subjected to internal review, and posted online for external public comment in September 2016. Guided by the International Classification of Functioning, Disability and Health framework, CDEs were categorized into six domains: (1) participant characteristics; (2) health, growth, and genetics; (3) neuroimaging; (4) neuromotor skills and functional assessments; (5) neurocognitive, social, and emotional assessments; and (6) engagement and quality of life. Version 1.0 of the NINDS/AACPDM CDEs for CP is publicly available on the NINDS CDE and AACPDM websites. Global use of CDEs for CP will standardize data collection, improve data quality, and facilitate comparisons across studies. Ongoing collaboration with international colleagues, industry, and people with CP and their families will provide meaningful feedback and updates as additional evidence is obtained. These CDEs are recommended for NINDS‐funded research for CP.What this paper adds This is the first comprehensive Common Data Elements (CDEs) for children and young people with CP for clinical research. The CDEs for children and young people with CP include common definitions, the standardization of case report forms, and measures. The CDE guides the standardization for data collection and outcome evaluation in all types of studies with children and young people with CP. The CDE ultimately improves data quality and data sharing.

147 Background: Prostate cancer patients treated with external beam radiation therapy are instructed to present daily with a full bladder to decrease small bowel and bladder toxicity and to increase reproducibility of treatment. However, older patients may have difficulty presenting with full bladders and variation of bladder volume with treatment is unknown. The objective of this study was to assess bladder filling at the time of radiation treatment (RT) using a bladder ultrasound in patients undergoing treatment for prostate cancer. Methods: Patients with prostate cancer were prospectively enrolled prior to CT simulation from January to August 2017. Bladder volume was recorded during CT simulation and daily immediately prior to RT. Patients were instructed to drink 8-12 ounces of water 30-60 minutes prior to RT. Three bladder volume measurements were recorded daily and averaged at the time of each treatment. Average bladder volume during treatment and the number of treatments with low bladder volumes ( < 50cc, < 60cc, and < 100cc) were reported using descriptive statistics. Results: A total of 13 patients completed a median of 42 days of RT during the study period, resulting in 550 daily bladder volumes. Ten patients were treated definitively and 3 with salvage radiation after prostatectomy. The median age of patients in the study was 72 years. Older patients were statistically more likely to present with low bladder volumes, with percentage of treatments with a bladder volume less than 50cc, 60cc, and 100cc being 29%, 42%, and 66% compared to only 4%, 7%, and 18% in patients aged < 70 (P < 0.01). The average bladder volume at the time of CT simulation was 176cc ± 57cc and the average volume during treatment was 140cc± 93cc, which was not statistically different (P = 0.28). The bladder volume did not significantly change over the course of treatment. Conclusions: Older patients (age 70+) with prostate cancer were more likely to present for RT with low bladder volumes in this prospective study. Our findings suggest that older patients should receive extra counseling about bladder filling and/or may require less bladder filling at the time of CT simulation to provide more accurate bowel dosimetry measurements.

Epidemiological studies propose a protective role for dietary fiber in colon cancer (CRC). One possible mechanism of fiber is its fermentation property in the gut and ability to change microbiota composition and function. Here, we investigate the role of a dietary fiber mixture in polyposis and elucidate potential mechanisms using TS4Cre × cAPCl°x468 mice. Stool microbiota profiling was performed, while functional prediction was done using PICRUSt. Stool short-chain fatty acid (SCFA) metabolites were measured. Histone acetylation and expression of SCFA butyrate receptor were assessed. We found that SCFA-producing bacteria were lower in the polyposis mice, suggesting a decline in the fermentation product of dietary fibers with polyposis. Next, a high fiber diet was given to polyposis mice, which significantly increased SCFA-producing bacteria as well as SCFA levels. This was associated with an increase in SCFA butyrate receptor and a significant decrease in polyposis. In conclusion, we found polyposis to be associated with dysbiotic microbiota characterized by a decline in SCFA-producing bacteria, which was targetable by high fiber treatment, leading to an increase in SCFA levels and amelioration of polyposis. The prebiotic activity of fiber, promoting beneficial bacteria, could be the key mechanism for the protective effects of fiber on colon carcinogenesis. SCFA-promoting fermentable fibers are a promising dietary intervention to prevent CRC.

ABSTRACT Cell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer in vitro in Enterococcus faecalis . To examine the role of pheromone signaling in vivo , we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF− recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF− recipient. While rescue of the CF− mating defect by coculture with CF+ recipients is easily accomplished in vitro , no extracellular complementation occurred in vivo . This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer in vivo . In the absence of CF+ recipients, a low level of transfer to CF− recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum. IMPORTANCE Horizontal gene transfer is a major factor in the biology of Enterococcus faecalis , an important nosocomial pathogen. Previous studies showing efficient conjugative plasmid transfer in the gastrointestinal (GI) tracts of experimental animals did not examine how the enterococcal sex pheromone response impacts the efficiency of transfer. Our study demonstrates for the first time pheromone-enhanced, high-frequency plasmid transfer of E. faecalis plasmid pCF10 in a mouse model in the absence of antibiotic or bacteriocin selection. Pheromone production by recipients dramatically increased plasmid transfer in germfree mice colonized initially with recipients, followed by donors. The presence of a coresident community of common gut microbes did not significantly reduce in vivo plasmid transfer between enterococcal donors and recipients. In mice colonized with enterococcal recipients, we detected plasmid transfer in the intestinal tract within 5 h of addition of donors, before transconjugants could be cultured from feces. Surprisingly, pCF10 carriage provided a competitive fitness advantage unrelated to antibiotic resistance or bacteriocin production.

ABSTRACT Rapid and accurate laboratory tests are important for the timely diagnosis and treatment of central nervous system infections. The FilmArray meningitis/encephalitis (ME) panel (BioFire Diagnostics, Salt Lake City, UT) is an FDA-cleared, multiplex molecular panel that allows the detection of 14 pathogens (bacterial [ n = 6], viral [ n = 7], and fungal [ n = 1] pathogens) from cerebrospinal fluid (CSF). In this study, we evaluated the performance characteristics of the FilmArray ME panel using clinical, residual CSF samples ( n = 291) that tested positive by a routine method(s) (e.g., bacterial culture, individual real-time PCR assay) for a pathogen represented on the ME panel. Of note, a subset ( n = 76) of the CSF specimens was collected during the prevaccine era and had been characterized as positive for a bacterial pathogen. The FilmArray ME panel demonstrated an overall percent positive agreement (PPA) of 97.5% (78/80) for bacterial pathogens, 90.1% (145/161) for viruses, and 52% (26/50) for Cryptococcus neoformans/C. gattii . Despite the low overall agreement (52%) between the ME panel and antigen testing for detection of C. neoformans/C. gattii , the percent positive agreement of the FilmArray assay for C. neoformans/C. gattii was 92.3% (12/13) when the results were compared directly to the results of routine fungal smear or culture. The FilmArray ME panel offers a rapid (∼60-min), syndrome-based approach for the detection of select meningitis and encephalitis pathogens.

Purpose FGFR genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with FGFR GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown. Patients and Methods Patients with CCA with FGFR GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with FGFR wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher’s exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis. Results Three hundred seventy-seven patients with CCA were identified, and 95 had FGFR GAs. FGFR2 GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, FGFR GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; P < .001), presented at an earlier stage (TNM stage I/II v III/IV: 35.8% v 22%, respectively; P = .001), and were associated with a longer OS compared with patients without FGFR GAs (37 v 20 months, respectively; P < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( P = .60) between CCA with FGFR2 fusions (n = 63) versus other FGFR GAs (n = 29). Patients with FGFR GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( P = .01). BAP1 mutation was the most common coexisting mutation without prognostic impact, whereas TP53 ( P = .04) and CDKN2A/B ( P = .04) were correlated with a shorter OS. Conclusion CCA with FGFR GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.