Double-power transformations to analyze data

Power transformations are commonly used in order to fit simpler and/or more appropriate models to data. These transformations are well-known and well-documented for cases where the predictor variables are not linearly constrained, unlike mixture experiments. In the case of mixture designs, however, for which linear constraints do exist, several linear models proposed in recent literature fall into a power transformation family; this suggests that similar transformations might be useful for mixture experiments, as well. The log-likelihood function for X and y, transformations on the response and predictor variables, was derived for the mixture case where the predictor variables are linearly constrained and was maximized using a specially-written SAS program. To test the effectiveness of this procedure, simulations were done for two different designs and for four different combinations of X, and y. It was found that the 95% confidence region about A and f captured the true values of X and y approximately 90% of the time, regardless of the nature of the design or of the transformation. This procedure appeared to be able to discriminate between the different transformations on the response better than on the predictor variables, particularly when the correct transformation was the log-transformation (i.e., when y = 0). This could be due in part to the fact that the ranges of the predictors chosen was simply not large enough given the amount of replication used

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

Introduction:Global data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system. Methods:The ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems. Results:This experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age. Conclusions:The achievement of global learning health systems will require further exploration, consensus-building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients

Effects of light intensity and dilution rate on the semicontinuous cultivation of Arthrospira (Spirulina) platensis. A kinetic Monod-type approach.

Abstract Semicontinuous cultures were carried out at different dilution rates (D) and light intensities (I) to determine the maximum productivity of Arthrospira platensis cultivated in helicoidal photobioreactor up to the achievement of pseudo-steady-state conditions. At I = 108 μmol photons m−2 s−1, the semicontinuous regime ensured the highest values of maximum cell concentration (Xm = 5772 ± 113 mg L−1) and productivity (PXS = 1319 ± 25 mg L−1 d−1) at the lowest (D = 0.1 day−1) and the highest (D = 0.3 day−1) dilution rates, respectively. A kinetic model derived from that of Monod was proposed to determine the relationship between the product of light intensity to dilution rate (ID) and the cell productivity, which were shown to exert a combined influence on this parameter. This result put into evidence that pseudo-steady-state conditions could be modified according to circumstances, conveniently varying one or other of the two independent variables

Effect of Thiotriazinone Impurity on Insoluble Microparticle Generation Associated with Ceftriaxone-calcium Salt Precipitation in Original (Rocephin®) and Japanese Generic Ceftriaxone Products

This study examined the effect of thiotriazinone impurity on the generation of insoluble microparticles (IMPs) associated with ceftriaxone-calcium salt precipitation in original (Rocephin®) and Japanese generic ceftriaxone (A; Sawai, B; Nichi-Iko) products when mixed with Ca2＋ 4.3mEq/l. We found that the generation rate of IMPs associated with ceftriaxone-calcium salt precipitation among the three ceftriaxone products tested was in the order of generic (A)＜original＜generic (B), as assessed by light obscuration particle counting. Typically, after 60 min, one of the generic ceftriaxone (B)-calcium mixtures was highly opaque with numerous aggregates of milky-white precipitates, the original ceftriaxone-calcium mixture exhibited noticeable IMPs, and the second generic ceftriaxone (A)-calcium mixture was transparent. The levels of thiotriazinone contaminants, known to be a major impurity in ceftriaxone products, were determined by HPLC and found to be in the order of generic A＞original＞generic B. Moreover, the addition of a small amount of thiotriazinone into the generic ceftriaxone (B)-calcium mixture significantly decreased the amount of IMPs, suggesting that the impurity retards ceftriaxone-calcium crystal growth. We thus concluded that the thiotriazinone impurity acts as a suppressive factor of ceftriaxone-calcium salt precipitation, and that the high level of thiotriazinone impurity in the ceftriaxone (B) product could underlie its lowest rate of IMP generation when mixed with calcium. We thus recommend caution regarding the clinical risk of ceftriaxone-calcium compatibility due to impurity contamination in ceftriaxone products

Mechanism of activation of the BNLF2a immune evasion gene of Epstein-Barr virus by Zta

The human gamma herpes virus Epstein–Barr virus (EBV) exploits multiple routes to evade the cellular immune response. During the EBV lytic replication cycle, viral proteins are expressed that provide excellent targets for recognition by cytotoxic T cells. This is countered by the viral BNLF2a gene. In B cells during latency, where BNLF2a is not expressed, we show that its regulatory region is embedded in repressive chromatin. The expression of BNLF2a mirrors the expression of a viral lytic cycle transcriptional regulator, Zta (BZLF1, EB1, ZEBRA), in B cells and we propose that Zta plays a role in up-regulating BNLF2a. In cells undergoing EBV lytic replication, we identified two distinct regions of interaction of Zta with the chromatin-associated BNLF2a promoter. We identify five potential Zta-response elements (ZREs) in the promoter that are highly conserved between virus isolates. Zta binds to these elements in vitro and activates the expression of the BNLF2a promoter in both epithelial and B cells. We also found redundancy amongst the ZREs. The EBV genome undergoes a biphasic DNA methylation cycle during its infection cycle. One of the ZREs contains an integral CpG motif. We show that this can be DNA methylated during EBV latency and that both Zta binding and promoter activation are enhanced by its methylation. In summary, we find that the BNLF2a promoter is directly targeted by Zta and that DNA methylation within the proximal ZRE aids activation. The implications for regulation of this key viral gene during the reactivation of EBV from latency are discussed

Polypharmacy and Clinical Outcomes in Hospitalized Patients With Acute Decompensated Heart Failure

BACKGROUND: Polypharmacy is a common problem among patients with acute decompensated heart failure (ADHF) who often have multiple comorbidities. OBJECTIVE: The aim of this study was to define the number of medications at hospital discharge and whether it is associated with clinical outcomes at 1 year. METHODS: We evaluated the number of medications in 2578 patients with ADHF who were ambulatory at hospital discharge in the Kyoto Congestive Heart Failure Registry and compared 1-year outcomes in 4 groups categorized by quartiles of the number of medications (quartile 1, ≤ 5; quartile 2, 6-8; quartile 3, 9-11; and quartile 4, ≥ 12). RESULTS: At hospital discharge, the median number of medications was 8 (interquartile range, 6-11) with 81.5% and 27.8% taking more than 5 and more than 10 medications, respectively. The cumulative 1-year incidence of a composite of death or rehospitalization (primary outcome measure) increased incrementally with an increasing number of medications (quartile 1, 30.8%; quartile 2, 31.6%; quartile 3, 39.7%; quartile 4, 50.3%; P < .0001). After adjusting for confounders, the excess risks of quartile 4 relative to those of quartile 1 remained significant (P = .01). CONCLUSIONS: In the contemporary cohort of patients with ADHF in Japan, polypharmacy at hospital discharge was common, and excessive polypharmacy was associated with a higher risk of mortality and rehospitalizations within a 1-year period. Collaborative disease management programs that include a careful review of medication lists and an appropriate deprescribing protocol should be implemented for these patients