Possibility of Using By-Products with High NDF Content to Alter the Fecal Short Chain Fatty Acid Profiles, Bacterial Community, and Digestibility of Lactating Dairy Cows.

This study aimed to investigate whether agricultural by-products with a high NDF content and small-particle-size substitute for forage could cause hindgut acidosis and dysbacteriosis in lactating dairy cows. We investigated the impact of soybean hull and beet pulp on the fecal fermentation, bacterial community, and digestibility of cows. Sixteen lactating Holstein cows were treated as follows (% of dry matter (DM)): amount of by-product added was 0 (control, CON), 1.67% (low by-products, LB), 3.33% (medium by-products, MB), and 5% (high by-products, HB). The results showed the fecal pH of cows to be 7.23-7.29, implying no hindgut acidosis. With increased inclusion of by-products in the diets, the proportion of fecal propionate; relative abundance of the phylum Bacteroidetes, the family Lachnospiraceae, and genera unclassified_f_Lachnospiraceae, Acetitomaculum, and Prevotella; and the DM and NDF digestibility of cows all increased linearly. Meanwhile, the fecal genera Turicibacter and Clostridium_sensu_stricto_1 decreased linearly. By-products promoted the abundance of fecal bacteria genes related to energy metabolism, glycolysis/gluconeogenesis, and propanoate metabolism; and correlations between fecal short chain fatty acids, digestibility, and the bacteria genera were seen. Overall, our study suggested that adding 5% by-products could be a viable dietary formulation strategy that promotes digestibility and makes positive changes in hindgut fermentation and bacteria.

Bayesian Sample Size Planning Tool for Phase I Dose-Finding Trials.

PURPOSE: Through Bayesian inference, we propose a method called BayeSize as a reference tool for investigators to assess the sample size and its associated scientific property for phase I clinical trials. METHODS: BayeSize applies the concept of effect size in dose finding, assuming that the maximum tolerated dose can be identified on the basis of an interval surrounding its true value because of statistical uncertainty. Leveraging a decision framework that involves composite hypotheses, BayeSize uses two types of priors, the fitting prior (for model fitting) and sampling prior (for data generation), to conduct sample size calculation under the constraints of statistical power and type I error. RESULTS: Simulation results showed that BayeSize can provide reliable sample size estimation under the constraints of type I/II error rates. CONCLUSION: BayeSize could facilitate phase I trial planning by providing appropriate sample size estimation. Look-up tables and R Shiny app are provided for practical applications.

M-CSF, IL-6, and TGF-ß promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery.

Traumatic brain injury (TBI) leads to high mortality rate. We aimed to identify the key cytokines favoring TBI repair and found that patients with TBI with a better outcome robustly increased concentrations of macrophage colony-stimulating factor, interleukin-6, and transforming growth factor-ß (termed M6T) in cerebrospinal fluid or plasma. Using TBI mice, we identified that M2-like macrophage, microglia, and endothelial cell were major sources to produce M6T. Together with the in vivo tracking of mCherry+ macrophages in zebrafish models, we confirmed that M6T treatment accelerated blood-borne macrophage infiltration and polarization toward a subset of tissue repair macrophages that expressed similar genes as microglia for neuroprotection, angiogenesis and cell migration. M6T therapy in TBI mice and zebrafish improved neurological function while blocking M6T-exacerbated brain injury. Considering low concentrations of M6T in some patients with poor prognostic, M6T treatment might repair TBI via generating a previously unidentified subset of tissue repair macrophages.

Long term follow-up and outcomes in adult patients with thalamic gliomas.

OBJECTIVES: To investigate the optimal treatment and prognosis of thalamic glioma in adult patients. PATIENTS AND METHODS: We retrospectively analyzed the adult patients with thalamic glioma admitted to our hospital from May 2005 to September 2016. Patients were divided into two groups according to their treatment: surgery-based combined treatment and intensity modulated radiation therapy (IMRT)-based treatment. Univariate chi-square test and multivariate logistic regression were used to identify independent factors for the treatment modality. A log-rank test, adjusting for propensity score, was used to compare the overall survival (OS) and progression-free survival (PFS) of patients between the two groups. RESULTS: Fifty-eight adult patients with thalamic gliomas were included in the analysis. Of them, 31 were treated with surgery-based treatment, and 27 were treated with IMRT-based treatment. The overall survival (OS) and progression-free survival (PFS) of patients between the two groups were not significantly different (median OS 16.0 (range 1.0-163.0) months vs. 10.0 (range 1.0-118.0) months, p = 0.344 and median PFS 10.0 (range 1.0-163.0) months vs. 6.0 (range 1.0-118.0) months, p = 0.464, respectively) even after adjusting for potential confounding factors. CONCLUSIONS: The OS and PFS of adult patients with thalamic glioma were not significantly different between patients in the surgical group and in the IMRT group. IMRT might be an acceptable alternative to surgery for adult patients with unresectable thalamic glioma.

Nonuniform depolarization properties of typical nanostructures and potential applications.

Nonuniform depolarization properties of ${\text{SiO}_2}$SiO2 thin film, two-dimensional (2D) Si grating, and three-dimensional Si cylinder grating, were systematically investigated by Lu-Chipman decomposition. We find that introducing surface profiles with dimensions comparable to the detecting wavelengths can lead to obvious nonuniform depolarization, and control of the sample azimuth can manipulate the uniformity of the depolarizer components. The results indicate that the 2D nanostructure shows obvious nonuniform depolarization at 0° and 90° azimuths, while almost uniform depolarization at 45° azimuth. These discovered phenomena may give rise to some potential applications, such as the detection of the existence of nanostructures without a priori information about the sample, and the design of a uniform or nonuniform depolarizer.

AAA: triple adaptive Bayesian designs for the identification of optimal dose combinations in dual-agent dose finding trials.

We propose a flexible design for the identification of optimal dose combinations in dual-agent dose finding clinical trials. The design is called AAA, standing for three adaptations: adaptive model selection, adaptive dose insertion and adaptive cohort division. The adaptations highlight the need and opportunity for innovation for dual-agent dose finding and are supported by the numerical results presented in the proposed simulation studies. To our knowledge, this is the first design that allows for all three adaptations at the same time. We find that AAA enhances the chance of finding the optimal dose combinations and shortens the trial duration. A clinical trial is being planned to apply the AAA design and a Web tool is being developed for both statisticians and non-statisticians.

Bayesian Adaptive Design for Finding the Maximum Tolerated Sequence of Doses in Multicycle Dose-Finding Clinical Trials.

PURPOSE: Statistical designs for traditional phase I dose-finding trials consider dose-limiting toxicity in the first cycle of treatment. In reality, patients often go through multiple cycles of treatment and may experience toxicity events in more than one cycle. Therefore, it is desirable to identify the maximum tolerated sequence of three doses across three cycles of treatment. METHODS: Motivated by a three-cycle dose-finding clinical trial for a rare cancer with a JAK inhibitor, we proposed and implemented a simple Bayesian adaptive dose-cycle finding (BaSyc) design that allows intercycle and intrapatient dose modification. Because of the patient-specific dosing strategy over cycles, the BaSyc design is suited as a method in precision oncology. RESULTS: BaSyc is simple and transparent because its algorithm can be summarized as two tabulated decision rules before the trial starts, allowing physicians to visually examine these rules. In addition, BaSyc employs a time-saving enrollment scheme that speeds up the trial. Extensive simulation studies show that BaSyc has desirable operating characteristics in identifying the maximum tolerated sequence. CONCLUSION: The BaSyc design provides a first-of-kind multicycle approach for dose finding and will likely lead to better and safer patient care and drug development.

Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis.

BACKGROUND: Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury. METHODS: We randomly assigned 36 patients who had had unilateral arm paralysis for more than 5 years to undergo C7 nerve transfer plus rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl-Meyer upper-extremity scale (scores range from 0 to 66, with higher scores indicating better function). Results The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. RESULTS: The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. CONCLUSIONS: In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, 13004466 .).

Relationship Between Air Quality and Outdoor Exercise Behavior in China: a Novel Mobile-Based Study.

PURPOSE: Based on data collected from an exercise app, the study aims to provide empirical evidence on the relationship between air quality and patterns of outdoor exercise in China. METHODS: Objective outdoor exercise data spanning 160 days were collected from 153 users of an exercise app, Tulipsport in China. Each exercise mode (running, biking, and walking, respectively) was organized into five air quality categories based on Air Quality Index (AQI): excellent, good, mild pollution, moderate pollution, and serious pollution. Key parameters of each app user were calculated and analyzed: the total number of exercise bouts, the average duration, and the average distance of each exercise mode in each air quality category. RESULTS: Multivariate analyses of variance indicate that the users were less likely to participate in outdoor running, biking, and walking (F = 24.16, p < .01, Wilk's Λ = 0.64) as levels of air pollution increased. However, there is no difference in terms of average distance and duration of exercise across different air pollution categories. CONCLUSIONS: People's participation in outdoor exercise is impeded by air pollution severity, but they stick to their exercise routines once exercise is initiated. Although people should protect themselves from health damages caused by exercising under pollution, the decreases in physical activity associated with air pollution may also pose an indirect risk to public health. The interactive relationship between air quality, exercise, and health warrants more empirical and interdisciplinary explorations.