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

Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families

International audienceBackground: Disulphide bridges are well known to play key roles in stability, folding and functions of proteins. Introduction or deletion of disulphides by site-directed mutagenesis have produced varying effects on stability and folding depending upon the protein and location of disulphide in the 3-D structure. Given the lack of complete understanding it is worthwhile to learn from an analysis of extent of conservation of disulphides in homologous proteins. We have also addressed the question of what structural interactions replaces a disulphide in a homologue in another homologue.Results: Using a dataset involving 34,752 pairwise comparisons of homologous protein domains corresponding to 300 protein domain families of known 3-D structures, we provide a comprehensive analysis of extent of conservation of disulphide bridges and their structural features. We report that only 54% of all the disulphide bonds compared between the homologous pairs are conserved, even if, a small fraction of the non-conserved disulphides do include cytoplasmic proteins. Also, only about one fourth of the distinct disulphides are conserved in all the members in protein families. We note that while conservation of disulphide is common in many families, disulphide bond mutations are quite prevalent. Interestingly, we note that there is no clear relationship between sequence identity between two homologous proteins and disulphide bond conservation. Our analysis on structural features at the sites where cysteines forming disulphide in one homologue are replaced by non-Cys residues show that the elimination of a disulphide in a homologue need not always result in stabilizing interactions between equivalent residues.Conclusion: We observe that in the homologous proteins, disulphide bonds are conserved only to a modest extent. Very interestingly, we note that extent of conservation of disulphide in homologous proteins is unrelated to the overall sequence identity between homologues. The non-conserved disulphides are often associated with variable structural features that were recruited to be associated with differentiation or specialisation of protein function

Can smoking initiation contexts predict how adult Aboriginal smokers assess their smoking risks? A cross-sectional study using the 'Smoking Risk Assessment Target'

Objectives: Smoking prevalence is slow to reduce among Indigenous Australians of reproductive age. We analysed the relationships between age of smoking initiation, recalled initiation influences and self-assessment of smoking risks in Aboriginal smokers. Design, setting and participants: A community-based cross-sectional survey of Aboriginal smokers aged 18–45 years (N=121; 58 men) was undertaken, using single-item measures. The Smoking Risk Assessment Target (SRAT) as the primary outcome measure enabled self-assessment of smoking risks from 12 options, recategorised into 3 groups. Participants recalled influences on their smoking initiation. Multinomial logistic regression modelling included age, gender, strength of urges to smoke, age at initiation (regular uptake) and statistically significant initiation influences on χ2 tests (‘to be cool’, alcohol and cannabis). Results: Frequent initiation influences included friends (74%; SD 0.44), family (57%; SD 0.5) and alcohol (40%; SD 0.49). 54% (n=65) of smokers had the highest risk perception on the SRAT, selected by those who cared about the smoking risks and intended to quit soon. On multivariate analyses, compared with the highest level of SRAT, male gender, lower age of uptake and strong urges to smoke were significantly associated with the lowest level of SRAT, selected by those who refuted risks or thought they could not quit. Lower age of uptake and alcohol were associated with mid-level of SRAT, selected by those who cared about smoking risks, but did not consider quitting as a priority. Conclusions: Characteristics of smoking initiation in youth may have far-reaching associations with how smoking risks are assessed by adults of reproductive age, and their intentions to quit smoking. Becoming a regular smoker at under the age of 16 years, and influences of alcohol on smoking uptake, were inversely associated with high-level assessment of smoking risks and intention to quit in regional Aboriginal smokers. The SRAT may help tailor approaches to Indigenous smoking cessation

LXR regulate cholesterol homeostasis in the proximal mouse epididymis.

Oxysterol nuclear receptors liver x receptors (LXRalpha and LXRbeta) regulate lipid homeostasis when cells have to face high amounts of cholesterol and/or fatty acids. Male mice invalidated for both lxr (LXR-/-) are infertile by 5 months of age, and become sterile by the age of 9 months. The epididymis was previously shown to be affected by the gene invalidation, a phenotype specifically located in the two proximal segments of this organ. We demonstrate here that cholesteryl esters are accumulated in a specific cell type of the epididymal epithelium, the apical cells, in these two first segments, in LXR-/- male mice. These accumulations are correlated to a decrease in the amount of a specific membrane cholesterol transporter, ATP-binding cassette A1 (ABCA1) in the caput epididymidis of LXR-/- mice. This decrease is due to a transcriptional down-regulation, and we further demonstrate that ABCA1, in the two first segments of the caput epididymidis, is located in the apical cells, and that its accumulation is lost in these cells for LXR-/- male mice as soon as 4 months of age. These data bring new elements in the cholesterol trafficking pathways in the epididymis, and will help a better understanding of the molecular mechanisms occurring in this organ in relation to the sperm cells maturation process

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

Getting to the Left of SHARP: Lessons Learned from West Point\u27s Efforts to Combat Sexual Harassment and Assault

View the Executive SummaryOn July 26, 1948, President Harry Truman signed Executive Order 9981, ending the practice of segregating the military services by race. That same year, the Army allowed women to join the services on an equal basis with men. Both of these steps preceded the larger societal changes that allowed fully equal treatment of all types of American citizens in military service. Just over 2 years ago, Congress repealed the Don’t Ask, Don’t Tell policy, allowing for gays and lesbians to openly take their place in the military. Our procedures and policies for successful gender integration have grown and evolved. The authors share five principles for leaders and commanders on the prevention of sexual harassment and assault, as well as associated “Tips” for implementation: (1) Leaders identify and break chains of circumstance; (2) Education is preferable to litigation; (3) What’s electronic is public; (4) Don’t ignore pornography; and, (5) Unit climate is the commander’s responsibility. These principles and their associated tips are not panaceas, and these recommendations are submitted for discussion and feedback.https://press.armywarcollege.edu/monographs/1468/thumbnail.jp

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

The Black Feminist Mixtape: A Collective Black Feminist Autoethnography of Black Women\u27s Existence in the Academy

Seven Black women graduate students from across different functional areas of higher education work in solidarity to write a collective Black Feminist Autoethnography (BFA) (Griffin, 2012) about our experiences at our respective colleges and universities. BFA is a theoretical and methodological means for Black female academics to critically narrate the pride and pain of Black womanhood (Griffin, 2012, p. 1). This article centers Black feminist scholarship as a framework to reflexively interpret how we as seven Black women navigate within, against, and beyond the academy to address dominant narratives that affect our professional and personal experiences. We use contemporary music lyrics and poems by Black women to actively illustrate and interrogate our individual and collective positionalities to promote critical literacy. Together, we are seven Black sista scholars who reclaim our voice as legitimized epistemologies in academic spaces. Hear Our Voices

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

Detection and imaging of the free radical DNA in cells—Site-specific radical formation induced by Fenton chemistry and its repair in cellular DNA as seen by electron spin resonance, immuno-spin trapping and confocal microscopy

Oxidative stress-related damage to the DNA macromolecule produces lesions that are implicated in various diseases. To understand damage to DNA, it is important to study the free radical reactions causing the damage. Measurement of DNA damage has been a matter of debate as most of the available methods measure the end product of a sequence of events and provide limited information on the initial free radical formation. We report a measurement of free radical damage in DNA induced by a Cu(II)-H2O2 oxidizing system using immuno-spin trapping supplemented with electron paramagnetic resonance. In this investigation, the short-lived radical generated is trapped by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) immediately upon formation. The DMPO adduct formed is initially electron paramagnetic resonance active, but is subsequently oxidized to the stable nitrone adduct, which can be detected and visualized by immuno-spin trapping and has the potential to be further characterized by other analytical techniques. The radical was found to be located on the 2′-deoxyadenosine (dAdo) moiety of DNA. The nitrone adduct was repaired on a time scale consistent with DNA repair. In vivo experiments for the purpose of detecting DMPO–DNA nitrone adducts should be conducted over a range of time in order to avoid missing adducts due to the repair processes