Clinical Utility of Multigene Profiling Assays in Early-Stage Invasive Breast Cancer: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)’s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors

Treadmill Platform for Quadrupedal Robots

Cal Poly Legged Robots, led by Professor Refvem and Professor Xing, has been leading Cal Poly’s attempts to simulate, produce, and test their legged robots. The initial testing of the locomotion of these robots can be dangerous to the robot since any bugs in the code could cause the robot to fall over and harm itself. Our responsibility as a team was to deliver a portable platform for testing the locomotion capabilities containing a fall prevention mechanism. In short, we have designed a platform for this purpose that consists of a treadmill surrounded by a wheeled chassis with a system of ropes, pulleys, and a winch for a fall prevention mechanism. Our method of lifting the robot is a success in two ways. First, our method only requires the addition of four eyebolts to the robot, a rather minor modification. Second, our method does not impede the motion of the robot when it is running normally. However, it was found that our method requires 1-1.7 seconds to lift the robot (depending on where the robot is located on the treadmill) – a rather crippling amount of time to lift a robot, seeing as how it is desired for the robot to run at 8 mph on the treadmill. Regardless, our design provides a great starting point for future Senior Project teams to improve upon it. It is our hope that our design will allow Cal Poly Legged Robots to further the development of legged robots and to generate interest, both at Cal Poly and hopefully around the world, in this area of study

Bulked-Segregant Analysis Coupled to Whole Genome Sequencing (BSA-Seq) for Rapid Gene Cloning in Maize

Forward genetics remains a powerful method for revealing the genes underpinning organismal form and function, and for revealing how these genes are tied together in gene networks. In maize, forward genetics has been tremendously successful, but the size and complexity of the maize genome made identifying mutant genes an often arduous process with traditional methods. The next generation sequencing revolution has allowed for the gene cloning process to be significantly accelerated in many organisms, even when genomes are large and complex. Here, we describe a bulked-segregant analysis sequencing (BSA-Seq) protocol for cloning mutant genes in maize. Our simple strategy can be used to quickly identify a mapping interval and candidate single nucleotide polymorphisms (SNPs) from whole genome sequencing of pooled F2 individuals. We employed this strategy to identify narrow odd dwarf as an enhancer of teosinte branched1, and to identify a new allele of defective kernel1. Our method provides a quick, simple way to clone genes in maize

Low oxygen delivery produced by anemia, hypoxia, and low cardiac output

In pentobarbital-anesthetized dogs, oxygen delivery (DO2) was measured by thermodilution cardiac output and cooximeter determined oxygen content, while oxygen consumption (VO2) was measured independently by spirometry. Oxygen delivery was decreased by isovolemic dilutional anemia, breathing hypoxic gas mixtures, or cardiac tamponade to reduce cardiac output. Baseline VO2 (cc/kg/min) for the three groups was 5.9 +/- 0.7 (anemia), 5.4 +/- 0.4 (hypoxia), and 5.6 +/- 0.1 (low C.O.) (NS). A critical level of oxygen delivery (DO2crit) was found at 9-10 cc/kg/min (anemia), 10-11 cc/kg/min (hypoxia), and 9-10 cc/kg/min (low C.O.) (NS.). Below this level, VO2 fell (became supply dependent) and lactic acidosis occurred, regardless of the mechanism of impaired oxygen delivery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29062/1/0000095.pd

Environmentalism, performance and applications: uncertainties and emancipations

This introductory article for a themed edition on environmentalism provides a particular context for those articles that follow, each of which engages with different aspects of environmentalism and performance in community-related settings. Responding to the proposition that there is a lacuna in the field of applied drama and environmentalism (Bottoms, 2010), we suggest that the more significant lack is that of ecocriticism. As the articles in this journal testify, there are many examples of applied theatre practice; what is required is sustained and rigorous critical engagement. It is to the gap of ecocriticism that we address this issue, signalling what we hope is the emergence of a critical field. One response to the multiple challenges of climate change is to more transparently locate the human animal within the environment, as one agent amongst many. Here, we seek to transparently locate the critic, intertwining the personal – ourselves, human actants – with global environmental concerns. This tactic mirrors much contemporary writing on climate change and its education, privileging personal engagement – a shift we interrogate as much as we perform. The key trope we anchor is that of uncertainty: the uncertainties that accompany stepping into a new research environment; the uncertainties arising from multiple relations (human and non-human); the uncertainties of scientific fact; the uncertainties of forecasting the future; and the uncertainties of outcomes – including those of performance practices. Having analysed a particular turn in environmental education (towards social learning) and the failure to successfully combine ‘art and reality’ in recent UK mainstream theatre events, such uncertainties lead to our suggestion for an ‘emancipated’ environmentalism. In support of this proposal, we offer up a reflection on a key weekend of performance practice that brought us to attend to the small – but not insignificant – and to consider first hand the complex relationships between environmental ‘grand narratives’ and personal experiential encounters. Locating ourselves within the field and mapping out some of the many conceptual challenges attached to it serves to introduce the territories which the following journal articles expand upon

Machine Learning Applications in the Neuro ICU: A Solution to Big Data Mayhem?

The neurological ICU (neuro ICU) often suffers from significant limitations due to scarce resource availability for their neurocritical care patients. Neuro ICU patients require frequent neurological evaluations, continuous monitoring of various physiological parameters, frequent imaging, and routine lab testing. This amasses large amounts of data specific to each patient. Neuro ICU teams are often overburdened by the resulting complexity of data for each patient. Machine Learning algorithms (ML), are uniquely capable of interpreting high-dimensional datasets that are too difficult for humans to comprehend. Therefore, the application of ML in the neuro ICU could alleviate the burden of analyzing big datasets for each patient. This review serves to (1) briefly summarize ML and compare the different types of MLs, (2) review recent ML applications to improve neuro ICU management and (3) describe the future implications of ML to neuro ICU management

Large-Area Electrodeposition of Few-Layer MoS2 on Graphene for 2D Material Heterostructures

Heterostructures involving two-dimensional (2D) transition metal dichalcogenides and other materials such as graphene have a strong potential to be the fundamental building block of many electronic and opto-electronic applications. The integration and scalable fabrication of such heterostructures is of essence in unleashing the potential of these materials in new technologies. For the first time, we demonstrate the growth of few-layer MoS2 films on graphene via non-aqueous electrodeposition. Through methods such as scanning and transmission electron microscopy, atomic force microscopy, Raman spectroscopy, energy and wavelength dispersive X-ray spectroscopies and X-ray photoelectron spectroscopy, we show that this deposition method can produce large-area MoS2 films with high quality and uniformity over graphene. We reveal the potential of these heterostructures by measuring the photo-induced current through the film. These results pave the way towards developing the electrodeposition method for the large-scale growth of heterostructures consisting of varying 2D materials for many applications.Comment: 11 pages and 6 figure

Cortical thickness is not associated with current depression in a clinical treatment study

BackgroundReduced cortical thickness is a candidate biological marker of depression, although findings are inconsistent. This could reflect analytic heterogeneity, such as use of region‐wise cortical thickness based on the Freesurfer Desikan–Killiany (DK) atlas or surface‐based morphometry (SBM). The Freesurfer Destrieux (DS) atlas (more, smaller regions) has not been utilized in depression studies. This could also reflect differential gender and age effects.MethodsCortical thickness was collected from 170 currently depressed adults and 52 never‐depressed adults. Visually inspected and approved Freesurfer‐generated surfaces were used to extract cortical thickness estimates according to the DK atlas (68 regions) and DS atlas (148 regions) for region‐wise analysis (216 total regions) and for SBM.ResultsOverall, except for small effects in a few regions, the two region‐wise approaches generally failed to discriminate depressed adults from nondepressed adults or current episode severity. Differential effects by age and gender were also rare and small in magnitude. Using SBM, depressed adults showed a significantly thicker cluster in the left supramarginal gyrus than nondepressed adults (P = 0.047) but there were no associations with current episode severity.ConclusionsThree analytic approaches (i.e., DK atlas, DS atlas, and SBM) converge on the notion that cortical thickness is a relatively weak discriminator of current depression status. Differential age and gender effects do not appear to represent key moderators. Robust associations with demographic factors will likely hinder translation of cortical thickness into a clinically useful biomarker. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. Hum Brain Mapp 38:4370–4385, 2017. © 2017 Wiley Periodicals, Inc.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138250/1/hbm23664_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138250/2/hbm23664.pd

Economic costs of biological invasions in the United Kingdom

Although the high costs of invasion are frequently cited and are a key motivation for environmental management and policy, synthesised data on invasion costs are scarce. Here, we quantify and examine the monetary costs of biological invasions in the United Kingdom (UK) using a global synthesis of reported invasion costs. Invasive alien species have cost the UK economy between US$6.9 billion and$17.6 billion (£5.4 – £13.7 billion) in reported losses and expenses since 1976. Most costs were reported for the entire UK or Great Britain (97%); country-scale cost reporting for the UK's four constituent countries was scarce. Reports of animal invasions were the costliest ($4.7 billion), then plant ($1.3 billion) and fungal ($206.7 million) invasions. Reported damage costs (i.e. excluding management costs) were higher in terrestrial ($4.8 billion) than aquatic or semi-aquatic environments ($29.8 million), and primarily impacted agriculture ($4.2 billion). Invaders with earlier introduction years accrued significantly higher total invasion costs. Invasion costs have been increasing rapidly since 1976, and have cost the UK economy $157.1 million (£122.1 million) per annum, on average. Published information on specific economic costs included only 42 of 520 invaders reported in the UK and was generally available only for the most intensively studied taxa, with just four species contributing 90% of species-specific costs. Given that many of the invasive species lacking cost data are actively managed and have well-recognised impacts, this suggests that cost information is incomplete and that totals presented here are vast underestimates owing to knowledge gaps. Financial expenditure on managing invasions is a fraction (37%) of the costs incurred through damage from invaders; greater investments in UK invasive species research and management are, therefore, urgently required

Patient-reported outcomes of brentuximab vedotin in Hodgkin lymphoma and anaplastic large-cell lymphoma

BACKGROUND: Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or R/R systemic anaplastic large-cell lymphoma (sALCL) treated with brentuximab vedotin (BV) experienced high remission rates in two Phase II trials. With increased response rates and survival times, patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are becoming increasingly important and can help inform treatment decisions to enhance care of cancer patients. OBJECTIVE: The objective was to qualitatively assess HRQoL in long-term survivors treated with BV. METHODS: An eight-question survey assessing PRO-related aspects was developed and fielded to a subset of patients with HL or sALCL who remained in long-term follow-up after completing BV treatment in the two pivotal studies. RESULTS: The survey was completed by 25 of 38 patients (12 with HL, 13 with sALCL). The majority of patients reported that their energy level, outlook on life, difficulties with daily activities, ability to participate in physical activities, and overall HRQoL improved compared to those before BV treatment. LIMITATIONS: Small sample size and lack of a baseline questionnaire or validated assessment instrument limit broad applicability of these findings to large populations of patients with HL or sALCL. CONCLUSION: This is the first report of BV PRO data in R/R HL and sALCL. Given the patients’ poor prognostic outcomes before stem cell transplant, these encouraging results warrant formal evaluation of PRO end points in BV trials