Quantitative measures of respect and social inclusion in children: overview and recommendations

An important task in empirical research on prejudice, respect and inclusion in children is the measurement of attitudes and behaviours. Although the literature on measuring attitudes and behaviour in adults is of some assistance, it is also clear that the task of measuring children’s attitudes and behaviour presents particular problems and challenges. We provide an overview in this paper of a number of currently used measures. Their strengths and limitations are outlined, and recommendations are made for contemporary practice. This review has been undertaken by the Una Quantitative Methods Learning Group. Una is a global learning initiative on children and ethnic diversity (see: www.unaglobal.org)

The MAPPINGS III Library of Fast Radiative Shock Models

We present a new library of fully-radiative shock models calculated with the MAPPINGS III shock and photoionization code. The library consists of grids of models with shock velocities in the range v=100-1000 km/s and magnetic parameters B/sqrt(n) of 10^-4 - 10 muG cm^(3/2) for five different atomic abundance sets, and for a pre-shock density of 1.0 cm^(-3). Additionally, Solar abundance model grids have been calculated for densities of 0.01, 0.1, 10, 100, and 1000 cm^(-3) with the same range in v and B/sqrt(n). Each model includes components of both the radiative shock and its photoionized precursor, ionized by the EUV and soft X-ray radiation generated in the radiative gas. We present the details of the ionization structure, the column densities, and the luminosities of the shock and its precursor. Emission line ratio predictions are separately given for the shock and its precursor as well as for the composite shock+precursor structure to facilitate comparison with observations in cases where the shock and its precursor are not resolved. Emission line ratio grids for shock and shock+precursor are presented on standard line ratio diagnostic diagrams, and we compare these grids to observations of radio galaxies and a sample of AGN and star forming galaxies from the Sloan Digital Sky Survey. This library is available online, along with a suite of tools to enable the analysis of the shocks and the easy creation of emission line ratio diagnostic diagrams. These models represent a significant increase in parameter space coverage over previously available models, and therefore provide a unique tool in the diagnosis of emission by shocks.Comment: 39 pages, 34 figures, accepted for publication in ApJS, April 200

Mitogen-activated protein kinase kinase 5 regulates proliferation and biosynthetic processes in procyclic forms of Trypanosoma brucei

The pathogenic protozoan T. brucei alternates into distinct developmental stages in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK) signaling pathways transduce extracellular stimuli into a range of cellular responses, which ultimately lead to the adaptation to the external environment. Here, we combined a loss of function approach with stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T. brucei. The silencing of MKK5 significantly decreased the proliferation of procyclic forms of T. brucei. To shed light on the molecular alterations associated with this phenotype, we measured the total proteome and phosphoproteome of cells silenced for MKK5. In the total proteome, we observed a general decrease in proteins related to ribosome and translation as well as down-regulation of several components of the fatty acids biosynthesis pathway. In addition, we observed alterations in the protein levels and phosphorylation of key metabolic enzymes, which point toward a suppression of the oxidative metabolism. Taken together, our findings show that the silencing of MKK5 alters cell growth, energy metabolism, protein and fatty acids biosynthesis in procyclic T. brucei

Virtues education in medical school: the foundation for professional formation

Background: Studies have shown that medical students have high rates of burnout accompanied by a loss of empathy as they progress through their training. This article describes a course for medical students at The University of Queensland-Ochsner Clinical School in New Orleans, LA, that focuses on the development of virtues and character strengths necessary in the practice of medicine. Staff of the Ochsner Clinical School and of the Institute of Medicine, Education, and Spirituality at Ochsner, a research and consulting group of Ochsner Health System, developed the course. It is a curricular innovation designed to explicitly teach virtues and their associated prosocial behaviors as a means of promoting professional formation among medical students. Virtues are core to the development of prosocial behaviors that are essential for appropriate professional formation. Methods: Fourth-year medical students receive instruction in the virtues as part of the required Medicine in Society (MIS) course. The virtues instruction consists of five 3-hour sessions during orientation week of the MIS course and a wrapup session at the end of the 8-week rotation. Six virtues—courage, wisdom, temperance, humanity, transcendence, and justice—are taught in a clinical context, using personal narratives, experiential exercises, contemplative practices, and reflective practices. Results: As of July 2015, 30 medical students had completed and evaluated the virtues course. Ninety-seven percent of students felt the course was well structured. After completing the course, 100% of students felt they understood and could explain the character strengths that improve physician engagement and patient care, 100% of students reported understanding the importance of virtues in the practice of medicine, and 83% felt the course provided a guide to help them deal with the complexities of medical practice. Ninety-three percent of students stated they would use the character strengths for their own well-being, and 90% said they would change their approach to the practice of medicine as a result of this course. Overall, 92% of students rated the course as outstanding or good. Conclusion: We developed a course to teach virtues and their associated prosocial behaviors that are important for the practice of medicine. After completing the course, students self-reported improved understanding of the virtues and their importance to the practice of medicine. We plan further studies to determine if participation in the course leads to less burnout and improved resilience

Native rodent species are unlikely sources of infection for Leishmania (Viannia) braziliensis along the Transoceanic Highway in Madre de Dios, Peru.

An estimated 2.3 million disability-adjusted life years are lost globally from leishmaniasis. In Peru's Amazon region, the department of Madre de Dios (MDD) rises above the rest of the country in terms of the annual incidence rates of human leishmaniasis. Leishmania (Viannia) braziliensis is the species most frequently responsible for the form of disease that results in tissue destruction of the nose and mouth. However, essentially nothing is known regarding the reservoirs of this vector-borne, zoonotic parasite in MDD. Wild rodents have been suspected, or proven, to be reservoirs of several Leishmania spp. in various ecosystems and countries. Additionally, people who live or work in forested terrain, especially those who are not regionally local and whose immune systems are thus naïve to the parasite, are at most risk for contracting L. (V.) braziliensis. Hence, the objective of this study was to collect tissues from wild rodents captured at several study sites along the Amazonian segment of the newly constructed Transoceanic Highway and to use molecular laboratory techniques to analyze samples for the presence of Leishmania parasites. Liver tissues were tested via polymerase chain reaction from a total of 217 rodents; bone marrow and skin biopsies (ear and tail) were also tested from a subset of these same animals. The most numerous rodent species captured and tested were Oligoryzomys microtis (40.7%), Hylaeamys perenensis (15.7%), and Proechimys spp. (12%). All samples were negative for Leishmania, implying that although incidental infections may occur, these abundant rodent species are unlikely to serve as primary reservoirs of L. (V.) braziliensis along the Transoceanic Highway in MDD. Therefore, although these rodent species may persist and even thrive in moderately altered landscapes, we did not find any evidence to suggest they pose a risk for L. (V.) braziliensis transmission to human inhabitants in this highly prevalent region

Number-related Brain Potentials Are Differentially Affected by Mapping Novel Symbols on Small versus Large Quantities in a Number Learning Task

The nature of the mapping process that imbues number symbols with their numerical meaning-known as the "symbolgrounding process"-remains poorly understood and the topic of much debate. The aim of this study was to enhance insight into how the nonsymbolic-symbolic number mapping process and its neurocognitive correlates might differ between small (1-4; subitizing range) and larger (6-9) numerical ranges. Hereto, 22 young adults performed a learning task in which novel symbols acquired numerical meaning by mapping them onto nonsymbolic magnitudes presented as dot arrays (range 1-9). Learning-dependent changes in accuracy and RT provided evidence for successful novel symbol quantity mapping in the subitizing (1-4) range only. Corroborating these behavioral results, the number processing related P2p component was only modulated by the learning/mapping of symbols representing small numbers 1-4. The symbolic N1 amplitude increased with learning independent of symbolic numerical range but dependent on the set size of the preceding dot array; it only occurred when mapping on one to four item dot arrays that allow for quick retrieval of a numeric value, on the basis of which, with learning, one could predict the upcoming symbol causing perceptual expectancy violation when observing a different symbol. These combined results suggest that exact nonsymbolic-symbolic mapping is only successful for small quantities 1-4 from which one can readily extract cardinality. Furthermore, we suggest that the P2p reflects the processing stage of first access to or retrieval of numeric codes and might in future studies be used as a neural correlate of nonsymbolic-symbolic mapping/symbol learning

A risk assessment tool for resumption of research activities during the COVID-19 pandemic for field trials in low resource settings

RATIONALE: The spread of severe acute respiratory syndrome coronavirus-2 has suspended many non-COVID-19 related research activities. Where restarting research activities is permitted, investigators need to evaluate the risks and benefits of resuming data collection and adapt procedures to minimize risk. OBJECTIVES: In the context of the multicountry Household Air Pollution Intervention (HAPIN) trial conducted in rural, low-resource settings, we developed a framework to assess the risk of each trial activity and to guide protective measures. Our goal is to maximize the integrity of reseach aims while minimizing infection risk based on the latest scientific understanding of the virus. METHODS: We drew on a combination of expert consultations, risk assessment frameworks, institutional guidance and literature to develop our framework. We then systematically graded clinical, behavioral, laboratory and field environmental health research activities in four countries for both adult and child subjects using this framework. National and local government recommendations provided the minimum safety guidelines for our work. RESULTS: Our framework assesses risk based on staff proximity to the participant, exposure time between staff and participants, and potential viral aerosolization while performing the activity. For each activity, one of four risk levels, from minimal to unacceptable, is assigned and guidance on protective measures is provided. Those activities that can potentially aerosolize the virus are deemed the highest risk. CONCLUSIONS: By applying a systematic, procedure-specific approach to risk assessment for each trial activity, we were able to protect our participants and research team and to uphold our ability to deliver on the research commitments we have made to our staff, participants, local communities, and funders. This framework can be tailored to other research studies conducted in similar settings during the current pandemic, as well as potential future outbreaks with similar transmission dynamics. The trial is registered with clinicaltrials.gov NCT02944682 on October 26. 2016

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases

Ranolazine Attenuates Trastuzumab-Induced Heart Dysfunction by Modulating ROS Production

The ErbB2 blocker trastuzumab improves survival in oncologic patients, but can cause cardiotoxicity. The late Na+ current inhibitor ranolazine has been shown to counter experimental HF, including doxorubicin cardiotoxicity (a condition characterized by derangements in redox balance), by lowering the levels of reactive oxygen species (ROS). Since ErbB2 can modulate ROS signaling, we tested whether trastuzumab cardiotoxicity could be blunted by ranolazine via redox-mediated mechanisms. Trastuzumab decreased fractional shortening and ejection fraction in mice, but ranolazine prevented heart dysfunction when co-administered with trastuzumab. Trastuzumab cardiotoxicity was accompanied by elevations in natriuretic peptides and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated with co-treatment with ranolazine. Trastuzumab also increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Interestingly, Neonatal Rat Ventricular Myocytes (NRVMs), labeled with MitoTracker Red and treated with trastuzumab, showed only a small increase in ROS compared to baseline conditions. We then stressed trastuzumab-treated cells with the beta-agonist isoproterenol to increase workload, and we observed a significant increase of probe fluorescence, compared with cells treated with isoproterenol alone, reflecting induction of oxidative stress. These effects were blunted by ranolazine, supporting a role for INa inhibition in the regulation of redox balance also in trastuzumab cardiotoxicity

Modulation of LISA free-fall orbits due to the Earth-Moon system

We calculate the effect of the Earth-Moon (EM) system on the free-fall motion of LISA test masses. We show that the periodic gravitational pulling of the EM system induces a resonance with fundamental frequency 1 yr^-1 and a series of periodic perturbations with frequencies equal to integer harmonics of the synodic month (9.92 10^-7 Hz). We then evaluate the effects of these perturbations (up to the 6th harmonics) on the relative motions between each test masses couple, finding that they range between 3mm and 10pm for the 2nd and 6th harmonic, respectively. If we take the LISA sensitivity curve, as extrapolated down to 10^-6 Hz, we obtain that a few harmonics of the EM system can be detected in the Doppler data collected by the LISA space mission. This suggests that the EM system gravitational near field could provide an absolute calibration for the LISA sensitivity at very low frequencies.Comment: 15 pages, 5 figure