Improving estimation and prediction in linear regression incorporating external information from an established reduced model

We consider a situation where there is rich historical data available for the coefficients and their standard errors in a linear regression model describing the association between a continuous outcome variable Y and a set of predicting factors X , from a large study. We would like to use this summary information for improving inference in an expanded model of interest, Y given X , B . The additional variable B is a new biomarker, measured on a small number of subjects in a new dataset. We formulate the problem in an inferential framework where the historical information is translated in terms of nonlinear constraints on the parameter space and propose both frequentist and Bayes solutions to this problem. We show that a Bayesian transformation approach proposed by Gunn and Dunson is a simple and effective computational method to conduct approximate Bayesian inference for this constrained parameter problem. The simulation results comparing these methods indicate that historical information on E( Y | X ) can improve the efficiency of estimation and enhance the predictive power in the regression model of interest E( Y | X , B ). We illustrate our methodology by enhancing a published prediction model for bone lead levels in terms of blood lead and other covariates, with a new biomarker defined through a genetic risk score.     

Antileishmanial effect of 3-aminooxy-1-aminopropane is due to polyamine depletion

The polyamines putrescine, spermidine, and spermine are organic cations that are required for cell growth and differentiation. Ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the polyamine biosynthetic pathway, catalyzes the conversion of ornithine to putrescine. As the polyamine biosynthetic pathway is essential for the growth and survival of Leishmania donovani, the causative agent of visceral leishmaniasis, inhibition of the pathway is an important leishmaniacidal strategy. In the present study, we examined for the first time the effects of 3-aminooxy-1-aminopropane (APA), an ODC inhibitor, on the growth of L. donovani. APA inhibited the growth of both promastigotes in vitro and amastigotes in the macrophage model, with the 50% inhibitory concentrations being 42 and 5 microM, respectively. However, concentrations of APA up to 200 microM did not affect the viability of macrophages. The effects of APA were completely abolished by the addition of putrescine or spermidine. APA induced a significant decrease in ODC activity and putrescine, spermidine, and trypanothione levels in L. donovani promastigotes. Parasites were transfected with an episomal ODC construct, and these ODC overexpressers exhibited significant resistance to APA and were concomitantly resistant to sodium antimony gluconate (Pentostam), indicating a role for ODC overexpression in antimonial drug resistance. Clinical isolates with sodium antimony gluconate resistance were also found to overexpress ODC and to have significant increases in putrescine and spermidine levels. However, no increase in trypanothione levels was observed. The ODC overexpression in these clinical isolates alleviated the antiproliferative effects of APA. Collectively, our results demonstrate that APA is a potent inhibitor of L. donovani growth and that its leishmaniacidal effect is due to inhibition of ODC.     

Relationship between nocturnal intraocular pressure-related peak recorded by contact lens sensor and disease progression in treated glaucomatous eyes

Purpose:The aim of this study is to study the association between Nocturnal Intraocular Pressure (IOP) related Peak recorded by a Contact Lens Sensor (CLS) and glaucoma progression in treated glaucomatous eyes.Methods:Institutional study in which forty glaucoma patients were recruited from glaucoma clinic. A total of 19 patients were labeled as progressors on current anti-glaucoma treatment despite controlled day time IOP whereas twenty one patients were clinically stable showing no progression. Worse eye of each patient was selected for placement of CLS. The timing of the highest signal (IOP related peak) was noted in 24 hour CLS graph and if it fell within the time frame of 11 pm to 5 am, it was labeled as ''nocturnal IOP related peak''.Results:Progressors were found to be significantly more prone to night spike than Non Progressors (χ² = 6.812; n = 40; P = 0.009), thus, showing a definite association between the two. Association between Nocturnal IOP related peak and various other variables like age, gender, mean daytime IOP and systemic illness was studied. A positive correlation was established between female gender and Nocturnal IOP related spike with a significantly higher proportion of females showing night spike than their male counterparts (χ² = 5.763; n = 40; P = 0.016). Other parameters did not show any significant relationship with Nocturnal IOP related spike.Conclusion:Dynamic 24 hour recording by CLS is beneficial in detecting nocturnal IOP-related peak, and thus, can potentially improve the clinical care of glaucoma patients, especially those showing progression.     

Trans-peritoneal vs. retroperitoneal robotic assisted partial nephrectomy in posterior renal tumours: need for a risk-stratified patient individualised approach. A systematic review and meta-analysis

Journal of Robotic Surgery - To systematically review world literature and compare peri-operative outcome including operating time (OT), estimated blood loss (EBL), warm ischemia time (WIT), length...     

Endoscopic endonasal versus transcranial approach to resection of olfactory groove meningiomas: a systematic review

Neurosurgical Review - Despite the increasing utility of the endoscopic endonasal approach (EEA) for management of anterior skull base (ASB) pathologies, the optimal treatment strategy for...     

A new class of bactericidal agents against S. aureus,MRSA and VRE derived from bisindolylmethane

A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact.     

A nine-year review of medicolegal claims in neurosurgery

Introduction

Neurosurgery remains among the highest malpractice risk specialties. This study aimed to identify areas in neurosurgery associated with litigation, attendant causes and costs.

Methods

Retrospective analysis was conducted of 42 closed litigation cases treated by neurosurgeons at one hospital between March 2004 and March 2013. Data included clinical event, timing and reason for claim, operative course and legal outcome.

Results

Twenty-nine claims were defended out of court and twelve were settled out of court. One case required court attendance and was defended. Of the 42 claims, 28, 13 and 1 related to spinal (0.3% of caseload), cranial (0.1% of caseload) and peripheral nerve (0.07% of caseload) surgery respectively. The most common causes of claims were faulty surgical technique (43%), delayed diagnosis/misdiagnosis (17%), lack of information (14%) and delayed treatment (12%), with a likelihood of success of 39%, 29%, 17% and 20% respectively. The highest median payouts were for claims against faulty surgical technique (£230,000) and delayed diagnosis/misdiagnosis (£212,650). The mean delay between clinical event and claim was 664 days.

Conclusions

Spinal surgery carries the highest litigation risk versus cranial and peripheral nerve surgery. Claims are most commonly against faulty surgical technique and delayed diagnosis/misdiagnosis, which have the highest success rates and payouts. In spinal surgery, the most common cause of claims is faulty surgical technique. In cranial surgery, the most common cause is lack of information. Claims may occur years after the clinical event, necessitating thorough contemporaneous documentation for adequate future defence. We emphasise thorough patient consultation and meticulous surgical technique to minimise litigation in neurosurgical practice.