Bayesian analysis of errors-in-variables in binary regression models

There has been considerable research done on the problems of errors-in-variables for linear regression. including a Bayesian solution by Lindley and EI-Sayyad (1968). Recently, interest has extended to binary regression and in particular probit regression. Burr (1985) performed frequentist analysis of Berkson's error in probit regression and found that the MLE does not ,always exist in finite samples. In this paper. we show that it is the tail behaviour of the likelihood that causes the problem and this in turn makes Bayesian estimation inadmissible if improper priors are used. Two non-informative priors are derived and simulation results indicate that the Bayesian solutions are generally superior to various likelihood based estimates, including the modified MLE proposed by Burr. It is further shown that the estimation problem vanishes if there are replicates and that the logistic model has the same behaviour as the probit model.postprin

Bayesian optimal designs for probit regression with errors-in-variables

Optimal design is the study of the choice of design points in an experiment. However, measurements are seldom precise in practical situations. If measurement error is substantial, it may ruin the whole experiment in that the objective of the experiment is not achieved. There is substantial literature on optimal designs, all based on the assumption that there is no measurement error in the covariates. For the Berkson error model, the observed design points are fixed by the experimenter but they deviate randomly from the pre-assigned level. In this paper, the Berkson error structure is incorporated into the probit regression model for which Bayesian D-optimal and A-optimal designs are studied. In addition, a new optimal design criterion is proposed.postprin

Control of Emi2 activity and stability through Mos-mediated recruitment of PP2A.

Before fertilization, vertebrate eggs are arrested in meiosis II by cytostatic factor (CSF), which holds the anaphase-promoting complex (APC) in an inactive state. It was recently reported that Mos, an integral component of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/Erp1. We report here that Rsk phosphorylation of Emi2 promotes its interaction with the protein phosphatase PP2A. Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding. An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be modulated by Mos. PP2A bound to Emi2 acted on two distinct clusters of sites phosphorylated by Cdc2, one responsible for modulating its stability during CSF arrest and one that controls binding to the APC. These findings provide a molecular mechanism for Mos action in promoting CSF arrest and also define an unusual mechanism, whereby protein phosphorylation recruits a phosphatase for dephosphorylation of distinct sites phosphorylated by another kinase

Hydrogen is neuroprotective against surgically induced brain injury

<p>Abstract</p> <p>Background</p> <p>Neurosurgical operations cause unavoidable damage to healthy brain tissues. Direct surgical injury as well as surgically induced oxidative stress contributes to the subsequent formation of brain edema. Therefore, we tested the neuroprotective effects of hydrogen (H₂) in an established surgical brain injury (SBI) model in rats.</p> <p>Materials and methods</p> <p>Adult male Sprague - Dawley rats (weight 300-350g) were divided into three groups to serve as sham operated, SBI without treatment, and SBI treated with H₂(2.9%). Brain water content, myeloperoxidase (MPO) assay, lipid peroxidation (LPO), and neurological function were measured at 24 hrs after SBI.</p> <p>Results</p> <p>SBI resulted in localized brain edema (p = < 0.001). Hydrogen (2.9%) administered concurrently with surgery significantly decreased the formation of cerebral edema (p = 0.028) and improved neurobehavioral score (p = 0.022). However, hydrogen treatment failed to reduce oxidative stress (LPO assay) or inflammation (MPO assay) in brain tissues.</p> <p>Conclusions</p> <p>Hydrogen appears to be promising as an effective, yet inexpensive way to reduce cerebral edema caused by surgical procedures. Hydrogen has the potential to improve clinical outcome, decrease hospital stay, and reduce overall cost to patients and the health care system.</p

Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

Aim: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group. This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism. Methods: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining. Results: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development. Conclusion: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Cap inflammation leads to higher plaque cap strain and lower cap stress: An MRI-PET/CT-based FSI modeling approach.

Plaque rupture may be triggered by extreme stress/strain conditions. Inflammation is also implicated and can be imaged using novel imaging techniques. The impact of cap inflammation on plaque stress/strain and flow shear stress were investigated. A patient-specific MRI-PET/CT-based modeling approach was used to develop 3D fluid-structure interaction models and investigate the impact of inflammation on plaque stress/strain conditions for better plaque assessment. 18FDG-PET/CT and MRI data were acquired from 4 male patients (average age: 66) to assess plaque characteristics and inflammation. Material stiffness for the fibrous cap was adjusted lower to reflect cap weakening causing by inflammation. Setting stiffness ratio (SR) to be 1.0 (fibrous tissue) for baseline, results for SR=0.5, 0.25, and 0.1 were obtained. Thin cap and hypertension were also considered. Combining results from the 4 patients, mean cap stress from 729 cap nodes was lowered by 25.2% as SR went from 1.0 to 0.1. Mean cap strain value for SR=0.1 was 0.313, 114% higher than that from SR=1.0 model. The thin cap SR=0.1 model had 40% mean cap stress decrease and 81% cap strain increase compared with SR=1.0 model. The hypertension SR=0.1 model had 19.5% cap stress decrease and 98.6% cap strain increase compared with SR=1.0 model. Differences of flow shear stress with 4 different SR values were limited (<10%). Cap inflammation may lead to large cap strain conditions when combined with thin cap and hypertension. Inflammation also led to lower cap stress. This shows the influence of inflammation on stress/strain calculations which are closely related to plaque assessment.This work was supported in part by NIH grants NIH/NIBIB R01 EB004759, NIH/NHLBI R01 HL071021, and National Natural Sciences Foundation of China grant 11672001, 11171030

A Retrospective Interventional Cohort Study to Assess the Safety and Efficacy of Sandostatin LAR for Treatment of Recurrent and/or Refractory Meningiomas.

Background: Meningiomas are the most common adult primary intracranial tumors in the United States. Despite high recurrence rate of atypical and malignant subtypes, there is no approved drug indicated specifically for meningioma. Since the majority of meningiomas exhibit high density of somatostatin receptors subtypes, somatostatin analogs have been under close investigation. The aim of this study was to evaluate efficacy and safety of Sandostatin LAR (octreotide) in patients with progressive, and/or recurrent meningioma, and identify subset of patients who were more likely to benefit from this treatment. Methods: A total of 43 patients ≥ 18 years old were included in the retrospective chart review. The patients underwent treatment with Sandostatin LAR (octreotide) from 01.01.2010 to 06.01.2017 at the University of California, Irvine after confirmation of the diagnosis. Six months progression free survival (PFS6) was defined as a primary endpoint, and the overall survival (OS), safety, and toxicity were identified as secondary endpoints. Results: The OS for 6 months, 1, and 3 years for all WHO grades was 94.8, 88.1, and 67.0%, respectively. The PFS6 for WHO I, II, III, and all was 89.4, 89, 33.3, and 80% respectively. For patients with no prior surgeries, chemotherapy or radiation, the PFS6 was 88.9, 84.8, and 94.8%, respectively. Interestingly, the PFS6 was 90.5% for skull-based and 80% for 3-6 cm tumors. Patients with tumors in parasagittal location had PFS6 of 83.3% compared to PFS6 of 50.0% for patients with convexity tumors. Evaluation of PFS6 based on the effect of estrogen and progesterone on meningioma identified that ER-PR+ tumors had PFS6 of 87.8% while patients with ER-PR- meningiomas had PFS6 of 62.5%. Median TTP for WHO grade I, II, and III was 3.1, 2.40, and 0.26 years, respectively. Subgroup analysis showed that median TTP was 3.1 years for &lt;3 cm tumors, 3.22 years for skull-based tumors, 2.37 years for patients with prior surgeries and 3.10 years for patients with no history of chemotherapy. History of radiation had no effect on median TTP. Sandostatin LAR (octreotide) was well-tolerated. Conclusions:This is one of the largest retrospective analysis of meningioma patients treated with Sandostatin LAR (octreotide) suggesting that this treatment has minimal to no adverse events and could prolong overall survival, and progression free survival especially for patients with ER-PR+ tumors who underwent surgeries for small skull-based tumors

To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing Antimicrobial Drug Development Must Become a Governmental Priority

This is the final version. Available on open access from the American Chemical Society via the DOI in this recorddata availability: This study did not generate any new data. The data on COVID-19 deaths used in the publication are publicly available at https://www.worldometers.info/coronavirus/ (access date 15th December 2020).The COVID-19 pandemic has refocused attention worldwide on the dangers of infectious diseases, in terms of both global health and the effects on the world economy. Even in high income countries, health systems have been found wanting in dealing with the new infectious agent. However, the even greater long-term danger of antimicrobial resistance in pathogenic bacteria and fungi is still under-appreciated, especially among the general public. Although antimicrobial drug development faces significant scientific challenges, the gravest challenge at the moment appears to be economic, where the lack of a viable market has led to a collapse in drug development pipelines. There is therefore a critical need for governments across the world to further incentivize the development of antimicrobials. Most incentive strategies over the past decade have focused on so-called “push” incentives that bridge the costs of antimicrobial research and development, but these have been insufficient for reviving the pipeline. In this Perspective, we analyze the current incentive strategies in place for antimicrobial drug development, and focus on “pull” incentives, which instead aim to improve revenue generation and thereby resolve the antimicrobial market failure challenge. We further analyze these incentives in a broader “One Health” context and stress the importance of developing and enforcing strict protocols to ensure appropriate manufacturing practices and responsible use. Our analysis reiterates the importance of international cooperation, coordination across antimicrobial research, and sustained funding in tackling this significant global challenge. A failure to invest wisely and continuously to incentivize antimicrobial pipelines will have catastrophic consequences for global health and wellbeing in the years to come.Wellcome TrustGCRF One Health Poultry HubMedical Research Council (MRC

Proceedings of the Second Annual Conference of the MidSouth Computational Biology and Bioinformatics Society

The MCBIOS 2004 conference brought together regional researchers and students in biology, computer science and bioinformatics on October 7th-9th 2004 to present their latest work. This editorial describes the conference itself and introduces the twelve peer-reviewed manuscripts accepted for publication in the Proceedings of the MCBIOS 2004 Conference. These manuscripts included new methods for analysis of high-throughput gene expression experiments, EST clustering, analysis of mass spectrometry data and genomic analysi