Strategies to mitigate bias from time recording errors in pharmacokinetic studies

Opportunistic pharmacokinetic (PK) studies have sparse and imbalanced clinical measurement data, and the impact of sample time errors is an important concern when seeking accurate estimates of treatment response. We evaluated an approximate Bayesian model for individualized pharmacokinetics in the presence of time recording errors (TREs), considering both a short and long infusion dosing pattern. We found that the long infusion schedule generally had lower bias in estimates of the pharmacodynamic (PD) endpoint relative to the short infusion schedule. We investigated three different design strategies for their ability to mitigate the impact of TREs: (i) shifting blood draws taken during an active infusion to the post-infusion period, (ii) identifying the best next sample time by minimizing bias in the presence of TREs, and (iii) collecting additional information on a subset of patients based on estimate uncertainty or quadrature-estimated variance in the presence of TREs. Generally, the proposed strategies led to a decrease in bias of the PD estimate for the short infusion schedule, but had a negligible impact for the long infusion schedule. Dosing regimens with periods of high non-linearity may benefit from design modifications, while more stable concentration-time profiles are generally more robust to TREs with no design modifications

AOIPS water resources data management system

A geocoded data management system applicable for hydrological applications was designed to demonstrate the utility of the Atmospheric and Oceanographic Information Processing System (AOIPS) for hydrological applications. Within that context, the geocoded hydrology data management system was designed to take advantage of the interactive capability of the AOIPS hardware. Portions of the Water Resource Data Management System which best demonstrate the interactive nature of the hydrology data management system were implemented on the AOIPS. A hydrological case study was prepared using all data supplied for the Bear River watershed located in northwest Utah, southeast Idaho, and western Wyoming

Pfizer

Pfizer was established in 1849 in Brooklyn, New York by cousins Charles Pfizer and Charles Erhart with a loan of $2,500 from Pfizer’s father.2 Today, 167 years later, Pfizer Inc. has international revenues of$49 billion, which makes it the second-largest pharmaceutical manufacturer in the world.3 Despite Pfizer’s success, the company has faced many challenges over the last few decades. The pharmaceutical industry is heavily influenced by legal, political, and technological forces, and all indications are that the industry will continue to experience dramatic changes

Evaluation of Noninvasive Respiratory Volume Monitoring in the PACU of a Low Resource Kenyan Hospital

This research aims to evaluate the use of the noninvasive respiratory volume monitor (RVM) compared to the standard of care (SOC) in the Post-Anesthesia Care Unit (PACU) of Kijabe Hospital, Kenya. The RVM provides real-time measurements for quantitative monitoring of non-intubated patients. Our evaluation was focused on the incidence of postoperative opioid-induced respiratory depression (OIRD). The RVM cohort (N = 50) received quantitative OIRD assessment via the RVM, which included respiratory rate, minute ventilation, and tidal volume. The SOC cohort (N = 46) received qualitative OIRD assessment via patient monitoring with oxygenation measurements (SpO2) and physical examination. All diagnosed cases of OIRD were in the RVM cohort (9/50). In the RVM cohort, participants stayed longer in the PACU and required more frequent airway maneuvers and supplemental oxygen, compared to SOC (all p \u3c 0.05). The SOC cohort may have had fewer diagnoses of OIRD due to the challenging task of distinguishing hypoventilation versus OIRD in the absence of quantitative data. To account for the higher OIRD risk with general anesthesia (GA), a subgroup analysis was performed for only participants who underwent GA, which showed similar results. The use of RVM for respiratory monitoring of OIRD may allow for more proactive care

The regulation of neutral amino acid transport in mammalian cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25214/1/0000654.pd

Expression of unprocessed glutelin precursor alters polymerization without affecting trafficking and accumulation

Rice glutelin is synthesized as a precursor in the endosperm endoplasmic reticulum and then deposited within the protein storage vacuole protein body-II (PB-II) as an aggregate, with a high degree of polymerized higher-order structure comprising mature acidic and basic subunits after post-translation processing cleavage. In order to investigate the functional role of this processing and its effect on folding assembly, wild-type GluA2 and its mutant cDNA (mGluA2), in which the conserved processing site (Asn-Gly) at the junction between the acidic and basic chains was replaced with Ala-Ala, were expressed under the control of the endosperm-specific GluB1 promoter in the mutant rice a123 line lacking glutelin GluA1, GluA2, and GluB4. The mGluA2 precursor was synthesized and stably targeted to PB-II without processing in the transgenic rice seeds like the wild-type GluA2. Notably, the saline-soluble mGluA2 precursor assembled with the other type of processed glutelin GluB as a trimer in PB-II, although such hetero-assembly with GluB was not detected in the transformant containing the processed GluA. Furthermore, the mGluA2 precursor in the glutelin fraction was deposited in PB-II by forming a quite different complex from the processed mature GluA2 products. These results indicate that post-translational processing of glutelin is not necessary for trafficking and stable accumulation in PB-II, but is required for the formation of the higher-order structure required for stacking in PB-II

Revealing a signaling role of phytosphingosine-1-phosphate in yeast

Perturbing metabolic systems of bioactive sphingolipids with genetic approachMultiple types of “omics” data collected from the systemSystems approach for integrating multiple “omics” informationPredicting signal transduction information flow: lipid; TF activation; gene expressio

Integrated Clustering and Anomaly Detection (INCAD) for Streaming Data (Revised)

Most current clustering based anomaly detection methods use scoring schema and thresholds to classify anomalies. These methods are often tailored to target specific data sets with "known" number of clusters. The paper provides a streaming clustering and anomaly detection algorithm that does not require strict arbitrary thresholds on the anomaly scores or knowledge of the number of clusters while performing probabilistic anomaly detection and clustering simultaneously. This ensures that the cluster formation is not impacted by the presence of anomalous data, thereby leading to more reliable definition of "normal vs abnormal" behavior. The motivations behind developing the INCAD model and the path that leads to the streaming model is discussed.Comment: 13 pages; fixes typos in equations 5,6,9,10 on inference using Gibbs samplin

A Smartphone-based Decision Support Tool Improves Test Performance Concerning Application of the Guidelines for Managing Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy

BACKGROUND: The American Society of Regional Anesthesia and Pain Medicine (ASRA) consensus statement on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy is the standard for evaluation and management of these patients. The authors hypothesized that an electronic decision support tool (eDST) would improve test performance compared with native physician behavior concerning the application of this guideline. METHODS: Anesthesiology trainees and faculty at 8 institutions participated in a prospective, randomized trial in which they completed a 20-question test involving clinical scenarios related to the ASRA guidelines. The eDST group completed the test using an iOS app programmed to contain decision logic and content of the ASRA guidelines. The control group completed the test by using any resource in addition to the app. A generalized linear mixed-effects model was used to examine the effect of the intervention. RESULTS: After obtaining institutional review board's approval and informed consent, 259 participants were enrolled and randomized (eDST = 122; control = 137). The mean score was 92.4 ± 6.6% in the eDST group and 68.0 ± 15.8% in the control group (P < 0.001). eDST use increased the odds of selecting correct answers (7.8; 95% CI, 5.7 to 10.7). Most control group participants (63%) used some cognitive aid during the test, and they scored higher than those who tested from memory alone (76 ± 15% vs. 57 ± 18%, P < 0.001). There was no difference in time to completion of the test (P = 0.15) and no effect of training level (P = 0.56). CONCLUSIONS: eDST use improved application of the ASRA guidelines compared with the native clinician behavior in a testing environment

Принципи та цілі логістичного обслуговування в контексті підвищення рівня конкурентоспроможності підприємства

In this article, we examine the digitalised emotional campaigning of one of Australia’s peak animal welfare body, Animals Australia, focusing on their most effective digital strategies associated with their campaigns against factory farming. Our broader interest lies with sounding out the affective affordances of the technologies informing such activist work; technologies of affect in a very significant sense. This discussion comprises three parts. First, we unpack the context for the problematic faced by animal and environmental activisms: neoliberalism, showing how neoliberal assumptions constrain such activisms to emotional appeals and denounce them for such strategising. Second, we sound out some of the affordances of digital media technologies for affectively oriented activisms; and finally, we delve into some of Animals Australia’s digital campaigning with regard to issues of factory farming in order to show the efficacy of such affectively oriented mediated strategising for the forming of new relations with factory farm. © 2017, © The Author(s) 2017