Effect of 3-Dimensional Virtual Reality Models for Surgical Planning of Robotic-Assisted Partial Nephrectomy on Surgical Outcomes: A Randomized Clinical Trial.

Importance: Planning complex operations such as robotic-assisted partial nephrectomy requires surgeons to review 2-dimensional computed tomography or magnetic resonance images to understand 3-dimensional (3-D), patient-specific anatomy. Objective: To determine surgical outcomes for robotic-assisted partial nephrectomy when surgeons reviewed 3-D virtual reality (VR) models during operative planning. Design, Setting, and Participants: A single-blind randomized clinical trial was performed. Ninety-two patients undergoing robotic-assisted partial nephrectomy performed by 1 of 11 surgeons at 6 large teaching hospitals were prospectively enrolled and randomized. Enrollment and data collection occurred from October 2017 through December 2018, and data analysis was performed from December 2018 through March 2019. Interventions: Patients were assigned to either a control group undergoing usual preoperative planning with computed tomography and/or magnetic resonance imaging only or an intervention group where imaging was supplemented with a 3-D VR model. This model was viewed on the surgeon\u27s smartphone in regular 3-D format and in VR using a VR headset. Main Outcomes and Measures: The primary outcome measure was operative time. It was hypothesized that the operations performed using the 3-D VR models would have shorter operative time than those performed without the models. Secondary outcomes included clamp time, estimated blood loss, and length of hospital stay. Results: Ninety-two patients (58 men [63%]) with a mean (SD) age of 60.9 (11.6) years were analyzed. The analysis included 48 patients randomized to the control group and 44 randomized to the intervention group. When controlling for case complexity and other covariates, patients whose surgical planning involved 3-D VR models showed differences in operative time (odds ratio [OR], 1.00; 95% CI, 0.37-2.70; estimated OR, 2.47), estimated blood loss (OR, 1.98; 95% CI, 1.04-3.78; estimated OR, 4.56), clamp time (OR, 1.60; 95% CI, 0.79-3.23; estimated OR, 11.22), and length of hospital stay (OR, 2.86; 95% CI, 1.59-5.14; estimated OR, 5.43). Estimated ORs were calculated using the parameter estimates from the generalized estimating equation model. Referent group values for each covariate and the corresponding nephrometry score were summed across the covariates and nephrometry score, and the sum was exponentiated to obtain the OR. A mean of the estimated OR weighted by sample size for each nephrometry score strata was then calculated. Conclusions and Relevance: This large, randomized clinical trial demonstrated that patients whose surgical planning involved 3-D VR models had reduced operative time, estimated blood loss, clamp time, and length of hospital stay. Trial Registration: ClinicalTrials.gov identifiers (1 registration per site): NCT03334344, NCT03421418, NCT03534206, NCT03542565, NCT03556943, and NCT03666104

INTEGRATE: Gene fusion discovery using whole genome and transcriptome data

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use

Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum

The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. Inhibition of protein farnesyltransferase (PFT) is lethal to the pathogenic protozoa Plasmodium falciparum. Parasites were isolated that were resistant to BMS-388891, a tetrahydroquinoline (THQ) PFT inhibitor. Resistance was associated with a 12-fold decrease in drug susceptibility. Genotypic analysis revealed a single point mutation in the beta subunit in resistant parasites. The resultant tyrosine 837 to cysteine alteration in the beta subunit corresponded to the binding site for the THQ and peptide substrate. Biochemical analysis of Y837C-PFT demonstrated a 13-fold increase in BMS-388891 concentration necessary for inhibiting 50% of the enzyme activity. These data are consistent with PFT as the target of BMS-388891 in P. falciparum and suggest that PFT inhibitors should be combined with other antimalarial agents for effective therapy

Firm-Specific Assets, Multinationality, and Financial Performance: A Meta-Analytic Review and Theoretical Integration

Through a meta-analysis of 120 independent samples reported in 111 studies, we test the predictions of internalization theory in the context of the multinationality-performance relationship. Findings indicate that multinationality provides an efficient organizational form that enables firms to transfer their firm-specific assets to generate higher returns in international markets. In addition, the results delineate the conditions under which firm-specific assets have the strongest impact on the multinationality-performance relationship. Meta-analytic evidence also suggests that multinationality has intrinsic value above and beyond the intangible assets that firms possess, given analyses controlling for firms\u27 international experience, age, size, and product diversification

The modern pollen-vegetation relationship of a tropical forest-savannah mosaic landscape, Ghana, West Africa

Transitions between forest and savannah vegetation types in fossil pollen records are often poorly understood due to over-production by taxa such as Poaceae and a lack of modern pollen-vegetation studies. Here, modern pollen assemblages from within a forest-savannah transition in West Africa are presented and compared, their characteristic taxa discussed, and implications for the fossil record considered. Fifteen artificial pollen traps were deployed for 1 year, to collect pollen rain from three vegetation plots within the forest-savannah transition in Ghana. High percentages of Poaceae and Melastomataceae/Combretaceae were recorded in all three plots. Erythrophleum suaveolens characterised the forest plot, Manilkara obovata the transition plot and Terminalia the savannah plot. The results indicate that Poaceae pollen influx rates provide the best representation of the forest-savannah gradient, and that a Poaceae abundance of >40% should be considered as indicative of savannah-type vegetation in the fossil record

Howard's War on Terror: A Conceivable, Communicable and Coercive Foreign Policy Discourse

This article explores the relationship between language and political possibility. It is argued that John Howard’s language from 11 September 2001 to mid 2003 helped to enable the ‘War on Terror’ in an Australian context in three principal ways. Firstly, through contingent and contestable constructions of Australia, the world and their relationship, Howard’s language made interventionism conceivable. Secondly, emphasising shared values, mateship and mutual sacrifice in war, Howard embedded his foreign policy discourse in the cultural terrain of ‘mainstream Australia’, specifically framing a foreign policy discourse that was communicable to ‘battlers’ and disillusioned ‘Hansonites’. Thirdly, positioning alternatives as ‘un-Australian’, Howard’s language was particularly coercive, silencing potential oppositional voices

Public perception of "scarless" surgery : a critical analysis of the literature

Evidence relating to the perception and view of patients and physicians on natural orifice transluminal endoscopic surgery (NOTES) and laparoendoscopic single-site surgery (LESS) was scrutinized. A comprehensive literature search was performed through PubMed. A total of 18 studies were included in the analysis. Patients demonstrated interest in scarless surgery, with a preference for LESS over NOTES. Safety and efficacy remain the key factors in the decision-making process of patients. With more information about the safety and reproducibility of LESS and NOTES, and with improved educational efforts, patients and physicians alike may feel more comfortable in widespread application of scarless surgery.(undefined

Curriculum Guidelines for Undergraduate Programs in Data Science

The Park City Math Institute 2016 Summer Undergraduate Faculty Program met for the purpose of composing guidelines for undergraduate programs in data science. The group consisted of 25 undergraduate faculty from a variety of institutions in the United States, primarily from the disciplines of mathematics, statistics, and computer science. These guidelines are meant to provide some structure for institutions planning for or revising a major in data science