African-American patients with cancer Talking About Clinical Trials (TACT) with oncologists during consultations: evaluating the efficacy of tailored health messages in a randomised controlled trial—the TACT study protocol

Introduction Low rates of accrual of African-American (AA) patients with cancer to therapeutic clinical trials (CTs) represent a serious and modifiable racial disparity in healthcare that impedes the development of promising cancer therapies. Suboptimal physician–patient consultation communication is a barrier to the accrual of patients with cancer of any race, but communication difficulties are compounded with AA patients. Providing tailored health messages (THM) to AA patients and their physician about CTs has the potential to improve communication, lower barriers to accrual and ameliorate health disparities. Objective (1) Demonstrate the efficacy of THM to increase patient activation as measured by direct observation. (2) Demonstrate the efficacy of THM to improve patient outcomes associated with barriers to AA participation. (3) Explore associations among preconsultation levels of: (A) trust in medical researchers, (B) knowledge and attitudes towards CTs, (C) patient-family member congruence in decision-making, and (D) involvement/information preferences, and group assignment. Methods and analysis First, using established methods, we will develop THM materials. Second, the efficacy of the intervention is determined in a 2 by 2 factorial randomised controlled trial to test the effectiveness of (1) providing 357 AA patients with cancer with THM with 2 different ‘depths’ of tailoring and (2) either providing feedback to oncologists about the patients\u27 trial THM or not. The primary analysis compares patient engaged communication in 4 groups preconsultation and postconsultation. Ethics and dissemination This study was approved by the Virginia Commonwealth University Institutional Review Board. To facilitate use of the THM intervention in diverse settings, we will convene ‘user groups’ at 3 major US cancer centres. To facilitate dissemination, we will post all materials and the implementation guide in publicly available locations

Evaluating The Robustness of Self-Supervised Representations to Background/Foreground Removal

Despite impressive empirical advances of SSL in solving various tasks, the problem of understanding and characterizing SSL representations learned from input data remains relatively under-explored. We provide a comparative analysis of how the representations produced by SSL models differ when masking parts of the input. Specifically, we considered state-of-the-art SSL pretrained models, such as DINOv2, MAE, and SwaV, and analyzed changes at the representation levels across 4 Image Classification datasets. First, we generate variations of the datasets by applying foreground and background segmentation. Then, we conduct statistical analysis using Canonical Correlation Analysis (CCA) and Centered Kernel Alignment (CKA) to evaluate the robustness of the representations learned in SSL models. Empirically, we show that not all models lead to representations that separate foreground, background, and complete images. Furthermore, we test different masking strategies by occluding the center regions of the images to address cases where foreground and background are difficult. For example, the DTD dataset that focuses on texture rather specific objects

Evaluating research impact: The development of a research for impact tool

© 2016 Tsey, Lawson, Kinchin, Bainbridge, McCalman, Watkin, Cadet-James and Rossetto. Introduction: This paper examines the process of developing a Research for Impact Tool in the contexts of general fiscal constraint, increased competition for funding, perennial concerns about the over-researching of Aboriginal and Torres Strait Islander issues without demonstrable benefits as well as conceptual and methodological difficulties of evaluating research impact. The aim is to highlight the challenges and opportunities involved in evaluating research impact to serve as resource for potential users of the research for impact tool and others interested in assessing the impact of research. Materials and methods: A combination of literature reviews, workshops with researchers, and reflections by project team members and partners using participatory snowball techniques. Results: Assessing research impact is perceived to be difficult, akin to the so-called "wicked problem," but not impossible. Heuristic and collaborative approach to research that takes the expectations of research users, research participants and the funders of research offers a pragmatic solution to evaluating research impact. The logic of the proposed Research for Impact Tool is based on the understanding that the value of research is to create evidence and/or products to support smarter decisions so as to improve the human condition. Research is, therefore, of limited value unless the evidence created is used to make smarter decisions for the betterment of society. A practical way of approaching research impact is, therefore, to start with the decisions confronting decision makers whether they are government policymakers, industry, professional practitioners, or households and the extent to which the research supports them to make smarter policy and practice decisions and the knock-on consequences of doing so. Embedded at each step in the impact planning and tracking process is the need for appropriate mix of expertise, capacity enhancement, and collaborative participatory learning-by-doing approaches. Discussion: The tool was developed in the context of Aboriginal and Torres Strait Islander research but the basic idea that the way to assess research impact is to start upfront with the information needs of decisions makers is equally applicable to research in other settings, both applied (horizontal) and basic (vertical) research. The tool will be further tested and evaluated with researchers over the next 2 years (2016/17). The decision by the Australian Government to include 'industry engagement' and 'impact' as additions to the Excellence in Research for Australia (ERA) quality measures from 2018 makes the Research for Impact Tool a timely development. The wider challenge is to engage with major Australian research funding agencies to ensure consistent alignment and approaches across research users, communities, and funders in evaluating impact

Protein Block Expert (PBE): a web-based protein structure analysis server using a structural alphabet

Encoding protein 3D structures into 1D string using short structural prototypes or structural alphabets opens a new front for structure comparison and analysis. Using the well-documented 16 motifs of Protein Blocks (PBs) as structural alphabet, we have developed a methodology to compare protein structures that are encoded as sequences of PBs by aligning them using dynamic programming which uses a substitution matrix for PBs. This methodology is implemented in the applications available in Protein Block Expert (PBE) server. PBE addresses common issues in the field of protein structure analysis such as comparison of proteins structures and identification of protein structures in structural databanks that resemble a given structure. PBE-T provides facility to transform any PDB file into sequences of PBs. PBE-ALIGNc performs comparison of two protein structures based on the alignment of their corresponding PB sequences. PBE-ALIGNm is a facility for mining SCOP database for similar structures based on the alignment of PBs. Besides, PBE provides an interface to a database (PBE-SAdb) of preprocessed PB sequences from SCOP culled at 95% and of all-against-all pairwise PB alignments at family and superfamily levels. PBE server is freely available at

No one's discussing the elephant in the room: Contemplating questions of research impact and benefit in Aboriginal and Torres Strait Islander Australian health research

© 2015 Bainbridge et al. Background: There remains a concern that Indigenous Australians have been over-researched without corresponding improvements in their health; this trend is applicable to most Indigenous populations globally. This debate article has a dual purpose: 1) to open a frank conversation about the value of research to Indigenous Australian populations; and 2) to stimulate ways of thinking about potential resolutions to the lack of progress made in the Indigenous research benefit debate. Discussion: Capturing the meaning of research benefit takes the form of ethical value-oriented methodological considerations in the decision-making processes of Indigenous research endeavours. Because research practices come from Western knowledge bases, attaining such positions in research means reconciling both Indigenous and Western knowledge systems to produce new methodologies that guide planning, evaluating and monitoring of research practices as necessary. Increasingly, more sophisticated performance measures have been implemented to ensure academic impact and benefits are captured. Assessing societal and other non-academic impacts and benefits however, has not been accorded corresponding attention. Research reform has only focussed on research translation in more recent years. The research impact debate must take account of the various standards of accountability (to whom), impact priorities (for whom), positive and negative impacts, and biases that operate in describing impact and measuring benefit. Summary: A perennial question in Indigenous research discourse is whether the abundance of research conducted; purportedly to improve health, is justified and benefits Indigenous people in ways that are meaningful and valued by them. Different research stakeholders have different conceptions of the value and nature of research, its conduct, what it should achieve and the kinds of benefits expected. We need to work collaboratively and listen more closely to the voice of Indigenous Australians to better understand, demonstrate and measure health research benefits. The authors conclude that as an imperative, a systematic benefit assessment strategy that includes identification of research priorities and planning, monitoring and evaluation components needs to be developed and implemented across research projects. In Indigenous health research, this will often mean adopting a benefit-led approach by changing the way research is done and preferencing alternative research methodologies. As a point of departure to improving impact and reaching mutually beneficial outcomes for researchers and partners in Indigenous health research, we need to routinise the assessment of benefit from outset of research as one of the standards toward which we work

Chronic Methamphetamine Administration Causes Differential Regulation of Transcription Factors in the Rat Midbrain

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning