While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

The complexity of biobank research raises concerns about individuals’ understanding of the information conveyed in the consent process for such research.. We report the results of a qualitative, cognitive interview study with an ethnically, linguistically, and educationally diverse sample of 43 respondents to assess the clarity and utility of a multimedia tool developed for a biobank. Using weighted randomization, respondents were assigned to either view the multimedia tool or read a written consent document . The study illustrates the utility of (...) cognitive interviews for gaining insights from prospective research participants about the clarity of informed consent tools. Findings suggest that a multimedia tool is useful for communicating key messages but should be combined with a written consent document and personal interaction with the study staff. We recommend that the potential value of multimedia tools should be more rigorously tested in a randomized controlled trial. (shrink)

Research Ethics Committees (RECs) are frequently a focus of complaints from researchers, but evidence about the operation and decisions of RECs tends to be anecdotal. We conducted a systematic study to identify and compare the ethical issues raised in 54 letters to researchers about the same 18 applications submitted to three RECs over one year. The most common type of ethical trouble identified in REC letters related to informed consent, followed by scientific design and conduct, care and protection of research (...) participants, confidentiality, recruitment and documentation. Community considerations were least frequently raised. There was evidence of variability in the ethical troubles identified and the remedies recommended. This analysis suggests that some principles may be more institutionalized than others, and offers some evidence of inconsistency between RECs. Inconsistency is often treated as evidence of incompetence and caprice, but a more sophisticated understanding of the role of RECs and their functioning is required. (shrink)

BACKGROUND: Hallucinations and delusions that complicate Parkinson’s disease could lead to nursing home placement and are linked to increased mortality. Cognitive impairments are typically associated with the presence of hallucinations but there are no data regarding whether such a relationship exists with delusions. OBJECTIVE: We hypothesized that hallucinations would be associated with executive and visuospatial disturbance. An exploratory examination of cognitive correlates of delusions was also completed to address the question of whether they differ from hallucinations. METHODS: 144 PD subjects (...) completed a neuropsychological battery to assess cognition and the SAPS to examine psychosis. Correlational analyses assessed associations between hallucinations and delusions with cognitive domains. RESULTS: 48 subjects reported psychotic symptoms: 25 experienced hallucinations without delusions, 23 had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. CONCLUSIONS: Cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations. Since this is a new finding, further studies will be needed to confirm our results. (shrink)

The precarious rights of senior citizens, especially those who are highly educated and who are expected to counsel and guide the younger generations, has stimulated the creation internationally of advocacy associations and opinion leader groups. The strength of these groups, however, varies from country to country. In some countries, they are supported and are the focus of intense interest; in others, they are practically ignored. For this is reason we believe that the creation of a network of all these associations (...) is essential. The proposed network would act as a support for the already-existing policies of the United Nations’ High Commission for Human Rights, of independent experts, and of the Global Alliance for the Rights of Older People. All three have long ago recommended the creation of a recognized instrument for uniting presently scattered efforts. The proposed network, therefore, will seek to promote the international exchange of relevant expertise, and it will reinforce the commitments and actions that single countries are currently taking to meet these objectives. For example, informative public events can be organised to promote particular support initiatives and to provide an opportunity for new members of the network to be presented. The network will promote health for senior citizens, disease prevention, senior mobility, safe free time for seniors, alimentary education, protection against new risks and dangers, as well as equity in the services necessary for seniors to adopt new information and communication technologies. In the case of retired academic members, the network will promote equality with respect to continuing use of digital technologies (particularly email), continuing access to research libraries, and the guaranteed ability for seniors to fund their own research programs and to deliver free seminars. (shrink)

The Dutch policy objective of a fully sustainable livestock sector without mutilations by 2023 is not compatible with the routine practice of tail docking to minimize the risk of tail biting. To examine farmer attitudes towards docking, a telephone survey was conducted among 487 conventional and 33 organic Dutch pig farmers. “Biting” (of tails, ears, or limbs) was identified by the farmers as a main welfare problem in pig farming. About half of the farmers reported to have no tail biting (...) problems in their own herd. When farmers did report problems, they most often reported figures between 1 and 5 % of the animals. High incidences of tail biting were anticipated when trying to keep undocked pigs. Enrichment materials used in the conventional sector included mainly chains (52–63 % of the farms) and hanging rubber or plastic balls (22–30 %). Straw, sawdust, or wood shavings was hardly provided in conventional pig farming (2–3 %), in contrast to organic farming (88–100 % of farms). Conventional pig farmers feel a curly tail is not very important for sustainable pig farming. They consider enrichment to be less effective and tail docking to be less stressful for them and their piglets than their organic colleagues do. Pig farmers identified climate as a main risk factor for tail biting as opposed to enrichment. The objective of reducing routine tail docking requires solutions for dealing with tail biting problems at the farm level. In this process, transfer of scientific knowledge about enrichment materials and other measures to prevent and cure tail biting is critical, as is a change in farmer attitudes and awareness of the moral issues involved. (shrink)

The Dutch policy objective of a fully sustainable livestock sector without mutilations by 2023 is not compatible with the routine practice of tail docking to minimize the risk of tail biting. To examine farmer attitudes towards docking, a telephone survey was conducted among 487 conventional and 33 organic Dutch pig farmers. “Biting” (of tails, ears, or limbs) was identified by the farmers as a main welfare problem in pig farming. About half of the farmers reported to have no tail biting (...) problems in their own herd. When farmers did report problems, they most often reported figures between 1 and 5 % of the animals. High incidences of tail biting were anticipated when trying to keep undocked pigs. Enrichment materials used in the conventional sector included mainly chains (52–63 % of the farms) and hanging rubber or plastic balls (22–30 %). Straw, sawdust, or wood shavings was hardly provided in conventional pig farming (2–3 %), in contrast to organic farming (88–100 % of farms). Conventional pig farmers feel a curly tail is not very important for sustainable pig farming. They consider enrichment to be less effective and tail docking to be less stressful for them and their piglets than their organic colleagues do. Pig farmers identified climate as a main risk factor for tail biting as opposed to enrichment. The objective of reducing routine tail docking requires solutions for dealing with tail biting problems at the farm level. In this process, transfer of scientific knowledge about enrichment materials and other measures to prevent and cure tail biting is critical, as is a change in farmer attitudes and awareness of the moral issues involved. (shrink)

Communicative Understandings of Women's Leadership Development: From Ceilings of Glass to Labyrinth Paths, edited by Elesha L. Ruminski and Annette M. Holba, weaves the disciplines of communication studies, leadership studies, and women's studies to offer theoretical and practical reflection about women's leadership development in academic, organizational, and political contexts. This work claims a space for women's leadership studies and acknowledges the paradigmatic shift from discussing women's leadership using the glass ceiling to what Eagly and Carli identify as the labyrinth of (...) leadership. (shrink)

Plamondon & Alimi's model will gain substantially in credibility when it is able to come up with predictions for new (rather than old) experimental results that discriminate between various models. Moreover, the present model is nothing more than a descriptive not an explanation for motor performance. A link to the contribution of various neuronal mechanisms involved in motor control and of muscle properties to the performance of the model is crucial.

Recent results have shown that the relative activation of muscles is different for isometric contractions and for movements. These results exclude an explanation of muscle activation patterns by a combination ofreciprocal and coactivation commands. These results also indicate that joint stiffness is not uniquely determined and that it may be different for isometric contractions and movements.

© The Authors 2017. Published by Oxford University Press on behalf of The Analysis Trust. All rights reserved. For Permissions, please email: [email protected] Clark is usually among the first in philosophy to ride a new and important wave on the frontiers of cognitive science research. His Microcognition and Associative Engines chronicled connectionism, Being There explored embodied cognition, Natural Born Cyborgs deals with BCIs and environmental and technological scaffolding, and Supersizing the Mind is an extended argument for extended minds. Clark's latest, (...) showcases his new enthusiasm about predictive coding, a computational framework for understanding cognition that is generating more excitement and controversy across diverse areas of cognitive science than an offshore wind at Maverick’s does among the boarding elite....Clark is a master at taking complex ideas in cognitive science and conveying them in less technical fashion to a wide audience, doing so with panache and wit.... (shrink)

A general practice research project on ethics is underway at the University of New South Wales, funded by GPEP. Ethical issues, as defined and explored by general practitioners and consumers, are being examined across four areas of Sydney.So far, telephone interviews have been conducted with a random sample of general practitioners. Face-to-face interviews have been conducted with 107 consumers, randomly sampled using ABS collection district information. Focus groups have been formed to discuss acceptable solutions to GP and consumer identified ethical (...) issues. This report will report on some preliminary findings to date and will explore professional and consumer roles in the formation of ethical solutions. (shrink)