While valuable work has been done addressing clinical ethics within established healthcare systems, we anticipate that the projected growth in acquisitions of community hospitals and facilities by large tertiary hospitals will impact the field of clinical ethics and the day-to-day responsibilities of clinical ethicists in ways that have yet to be explored. Toward the goal of providing clinical ethicists guidance on a range of issues that they may encounter in the systematization process, we discuss key considerations and potential challenges in (...) implementing system-wide ethics consultation services. Specifically, we identify four models for organizing, developing, and enhancing ethics consultation activities within a system created through acquisitions: train-the-trainer, local capacity-building, circuit-riding, and consolidated accountability. We note each model’s benefits and challenges. To our knowledge, this is the first paper to consider the broader landscape of issues affected by consolidation. We anticipate that clinical ethicists, volunteer consultants, and hospital administrators will benefit from our recommendations. (shrink)

More than a decade after Philip P. Wiener and Frederick H. Young edited the first volume of Studies in the Philosophy of Charles Sanders Peirce, Moore and Robin have brought together a collection of essays which serves as a valuable supplement to that earlier publication. It is more than a supplement, however; it can stand on its own as a significant contribution to Peirce scholarship. Continuity with the first volume is achieved through new essays which analyze Peirce's theory of belief, (...) of habit, and of Scotistic realism—themes about which many of the earlier papers revolved. Novelty is achieved through increased emphasis on Peirce's logical and mathematical writings and on the influence of nineteenth century evolutionism upon Peirce's pragmaticism. The exploration of the latter motif in the three contributions of W. Donald Oliver, Rulon Wells, and Thomas A. Goudge is particularly noteworthy. In their Preface, Moore and Robin state that the most significant contribution of this new volume is the revelation of the extent to which Peirce was first a scientist and then a philosopher. This is a misleading characterization of the book. True, Victor F. Lenzen's "Charles S. Peirce As Astronomer" is an engaging piece. On the other hand, the bulk of the articles impress the reader with the originality and modernity of Peirce, the philosopher and Peirce, the logician. The most notable feature of this collection is the number of essays which draw parallels between dominant philosophical and logical themes found in Peirce's writings and major interests of mid-twentieth century philosophers. Impressive examples are: A. R. Turquette's "Peirce's Icons For Deductive Logic," Richard M. Martin's "On Acting On A Belief," Larry Holmes's "Prolegomena To Peirce's Philosophy Of Mind," and Richard J. Bernstein's "Peirce's Theory of Perception." In presenting the articles which constitute this volume the editors give evidence not only of the relevance of Peirce for the contemporary student of philosophy but also of the impetus which Peirce's thought has provided for creative philosophical analysis. An additional bonus for Peirce scholars are two bibliographies prepared by Max H. Fisch. One is a supplement to Arthur W. Burk's 1958 bibliography of works by C. S. Peirce. The other is a draft of a bibliography of works about C. S. Peirce.—B. G. R. (shrink)

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)

En este artículo exponemos algunas mejoras y aportaciones en dos aspectos de los sistemas de gestión de aprendizaje (LMS). El primer aspecto es la seguridad y la autenticación, donde presentamos una modalidad de combinar la autenticación tradicional de contraseña y nombre de usuario con la autenticación por la técnica biométrica de comparación de huellas dactilares. El segundo aspecto es una arquitectura middleware capaz de dar acceso desde los LMS a distintos laboratorios remotos y virtuales (online) de forma que, se evita (...) la duplicación de los servicios proporcionados por ambas y se reutilizan los servicios proporcionados por los LMS en las sesiones prácticas. (shrink)

We solve a longstanding question of Soare by showing that if ${\mathbf d}$ is a non-low $_2$ computably enumerable degree then ${\mathbf d}$ contains a c.e. set with no r-maximal c.e. superset.

Graphical AbstractGene editing with engineered nucleases introduce double-strand breaks that are repaired by error-prone nonhomologous end-joining (NHEJ). In article number 1900126, Sara G. Trimidal et al. propose that the length and type or resulting indels can now be controlled by editing with different engineered nucleases or by manipulating the expression of NHEJ genes.

Executive functions represent higher order top-down mechanisms regulating information processing. While suboptimal EF have been studied in various patient groups, their impact on successful behavior is still not well described. Previously, it has been suggested that design fluency —a test including several simultaneous EF components mainly related to fluency, cognitive flexibility, and creativity—predicts successful behavior in a quickly changing environment where fast and dynamic adaptions are required, such as ball sports. We hypothesized that similar behaviors are of importance in the (...) selection process of elite police force applicants. To test this hypothesis, we compared elite police force applicants with a control group of police officer trainees. Although both groups were better than the norm, the elite police force applicants had a significantly better performance in DF total correct when adjusting for sex and age [F = 18.98, p < 0.001]. To understand how this capacity was altered by stress and tiredness, we re-tested the elite police force applicants several days during an extreme field assessment lasting 10 days. The results suggested that there was a lower than expected improvement in DF total correct and a decline in the DF3-subtest that includes a larger component of cognitive flexibility than the other subtests. Although there was a positive correlation between the baseline session and the re-test in DF3 [r = 0.49, p = 0.001], the applicants having the highest scores in the baseline test also displayed the largest percentage decline in the re-test [r = −0.46, p = 0.003]. In conclusion, our result suggests that higher order EF that include cognitive flexibility and creativity are of importance in the application for becoming an elite police officer but relatively compromised in a stressful situation. Moreover, as the decline is different between the individuals, the results suggest that applicants should be tested during baseline conditions and during stressful conditions to describe their cognitive capacity fully. (shrink)

In people with chronic low back pain, maladaptive structural and functional changes on a cortical level have been identified. On a functional level, somatosensory cortical excitability has been shown to be reduced in chronic pain conditions, resulting in cortical disinhibition. The occurrence of structural and/or functional maladaptive cortical changes in people with CLBP could play a role in maintaining the pain. There is currently no measurement protocol for cortical excitability that employs stimulation directly to the lower back. We developed a (...) protocol for the measurement of single pulse somatosensory evoked potential waveforms and paired-pulse behavior generated from sensory nerves of the lower back and quantified its test–retest reliability in a sample of 30 healthy individuals to gain insights into the normal variability of cortical responses, which could then be compared to results from people with CLBP. We investigated cortical excitability by measuring SEPs and PPB. PPB was defined as the ratio of the amplitude of the second cortical response divided by the first cortical response. A2s was determined by subtracting the response to single-pulse stimuli from the paired pulse stimuli response to account for linear superposition effects. The test–retest reliability of the protocol was very poor with no evidence of systematic bias but a high amount of random variability between sessions. There was no significant difference in the right side PPB for session 1 and session 2 ; mean session difference [ = −0.44 ; t = −1.17, p = 0.26]. The ICC3.1 for the outlier-removed right side PPB were 0.19 and 0.43 for left side PPB. This finding potentially has wider implications for PPB protocols. If these findings were replicated in other groups and other nerves, it would question the validity of this measure more generally. However, these findings are restricted to healthy people and sensory nerves of the lower back and may not be generalizable. (shrink)

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits (...) can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w. (shrink)

Synaesthesia is a condition in which one type of stimulation evokes the sensation of another, as when the hearing of a sound produces photisms, i.e. mental percepts of colours. R is a 20 year old colour blind subject who, in addition to the relatively common grapheme-colour synaesthesia, presents a rarely reported cross modal perception in which a variety of visual stimuli elicit aura-like percepts of colour. In R, photisms seem to be closely related to the affective valence of stimuli and (...) typically bring out a consistent pattern of emotional responses. The present case study suggests that colours might be an intrinsic category of the human brain. We developed an empirical methodology that allowed us to study the subject's otherwise inaccessible phenomenological experience. First, we found that R shows a Stroop effect (delayed response due to interference) elicited by photisms despite the fact that he does not show a regular Stroop with real colours. Secondly, by manipulating the colour context we confirmed that colours can alter R's emotional evaluation of the stimuli. Furthermore, we demonstrated that R's auras may actually lead to a partially inverted emotional spectrum where certain stimuli bring out emotional reactions opposite to the normal ones. These findings can only be accounted for by considering R's subjective colour experience or qualia. Therefore the present paper defends the view that qualia are a useful scientific concept that can be approached and studied by experimental methods. (shrink)

Synaesthesia is a condition in which one type of stimulation evokes the sensation of another, as when the hearing of a sound produces photisms, i.e. mental percepts of colours. R is a 20 year old colour blind subject who, in addition to the relatively common grapheme-colour synaesthesia, presents a rarely reported cross modal perception in which a variety of visual stimuli elicit aura-like percepts of colour. In R, photisms seem to be closely related to the affective valence of stimuli and (...) typically bring out a consistent pattern of emotional responses. The present case study suggests that colours might be an intrinsic category of the human brain. We developed an empirical methodology that allowed us to study the subject's otherwise inaccessible phenomenological experience. First, we found that R shows a Stroop effect elicited by photisms despite the fact that he does not show a regular Stroop with real colours. Secondly, by manipulating the colour context we confirmed that colours can alter R's emotional evaluation of the stimuli. Furthermore, we demonstrated that R's auras may actually lead to a partially inverted emotional spectrum where certain stimuli bring out emotional reactions opposite to the normal ones. These findings can only be accounted for by considering R's subjective colour experience or qualia. Therefore the present paper defends the view that qualia are a useful scientific concept that can be approached and studied by experimental methods. (shrink)

The dorsal anterior cingulate cortex is a key node in the human salience network. It has been ascribed motor, pain-processing and affective functions. However, the dynamics of information flow in this complex region and how it responds to inputs remain unclear and are difficult to study using non-invasive electrophysiology. The area is targeted by neurosurgery to treat neuropathic pain. During deep brain stimulation surgery, we recorded local field potentials from this region in humans during a decision-making task requiring motor output. (...) We investigated the spatial and temporal distribution of information flow within the dACC. We demonstrate the existence of a distributed network within the anterior cingulate cortex where discrete nodes demonstrate directed communication following inputs. We show that this network anticipates and responds to the valence of feedback to actions. We further show that these network dynamics adapt following learning. Our results provide evidence for the integration of learning and the response to feedback in a key cognitive region. (shrink)

Through the analysis of forty ethical dilemmas drawn from real-life situations, _Ethics in Action_ guides the reader through a process of moral deliberation that leads to the resolution of a variety of moral dilemmas. Fosters critical thinking by evaluating the reasons people give to support their choices and actions Challenges the paradigm of moral relativism that often impedes efforts to resolve moral dilemmas Incorporates international perspectives often lacking in texts published for a U.S. audience.

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)