576 research outputs found

    Effect of dietary fatty acid composition on depot fat and exercise performance in a migrating songbird, the red-eyed vireo

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    Most migrating birds accumulate lipid stores as their primary source of energy for fueling long distance flights. Lipid stores of birds during migration are composed of mostly unsaturated fatty acids; whether such a fatty acid composition enhances exercise performance of birds is unknown. We tested this hypothesis by measuring metabolic rate at rest and during intense exercise in two groups of red-eyed vireos, a long-distance migratory passerine, fed either a diet containing 82% unsaturated fat (82%U), or one containing 58% unsaturated fat (58%U). Vireos fed the 82%U diet had fat stores containing (77%) unsaturated fatty acids, whereas vireos fed the 58% U diet had fat stores containing less (66%) unsaturated fatty acids. Blood metabolites measured prior to and immediately following exercise confirmed that vireos were metabolizing endogenous fat during intense exercise. Mass-specific resting metabolic rate (RMR) was similar for vireos fed the 58%U diet (2.75±0.32 ml O2 g–1 h–1) and for vireos fed the 82%U diet (2.30±0.30 ml O2 g–1 h–1). However, mass-specific peak metabolic rate (MRpeak) was 25% higher in vireos fed the 58%U diet (28.55±1.47 ml O2 g–1 h–1) than in vireos fed the 82%U diet (21.50±1.76 ml O2 g–1 h–1). Such whole-animal energetic effects of fatty acid composition of birds suggest that the energetic cost of migration in birds may be affected by the fatty acid composition of the diet

    Working towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique study

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    BACKGROUND: Eliciting adverse event (AE) and non-study medication data reports from clinical research participants is integral to evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of anti-malarials in vulnerable populations, and their increasing use in healthy, but at-risk individuals, as preventive treatment or to reduce malaria transmission. METHODS: Experienced and knowledgeable anti-malarial drug clinical researchers were invited to participate in a Delphi technique study, to facilitate consensus on what are considered optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. RESULTS: Of 72 invited, 25, 16 and 10 panellists responded to the first, second and third rounds of the Delphi, respectively. Overall, 68% (68/100) of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed on the utility of a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of specific signs and symptoms questions were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. CONCLUSIONS: This study succeeded in reaching consensus within a section of the anti-malarial drug clinical research community about using a general question concept, and structured questions for eliciting data about AEs and non-study medication reports. The concepts and items considered in this Delphi to be relevant, important and feasible should be further investigated for potential inclusion in a harmonized approach to collect participant-elicited anti-malarial drug safety data. This, in turn, should improve understanding of anti-malarial drug safety

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

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    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

    The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia

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    Acute myeloid leukemia (AML) is a largely incurable disease, for which new treatments are urgently needed. While leukemogenesis occurs in the hypoxic bone marrow, the therapeutic tractability of the hypoxia-inducible factor (HIF) system remains undefined. Given that inactivation of HIF-1α/HIF-2α promotes AML, a possible clinical strategy is to target the HIF-prolyl hydroxylases (PHDs), which promote HIF-1α/HIF-2α degradation. Here, we reveal that genetic inactivation of Phd1/Phd2 hinders AML initiation and progression, without impacting normal hematopoiesis. We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to disable pro-leukemogenic pathways, re-program metabolism and induce apoptosis, in part via upregulation of BNIP3. Notably, concurrent inhibition of BCL-2 by venetoclax potentiates the anti-leukemic effect of PHD inhibition. Thus, PHD inhibition, with consequent HIF-1α stabilization, is a promising nontoxic strategy for AML, including in combination with venetoclax

    The Social Studies Curriculum in Atlanta Public Schools During the Desegregation Era

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    This historical investigation explores how teachers, students, and education officials viewed the social studies curriculum in the local context of Atlanta, and the broader state of Georgia, during the post-Civil Rights era, when integration was a court-ordered reality in the public schools. During the desegregation era, Atlanta schools were led by Atlanta Public Schools (APS) Superintendent, Dr. Alonzo Crim. Brought to Atlanta as part of a desegregation compromise, Dr. Crim became APS\u27s first African American superintendent. In particular, the authors investigate how national social studies movements, such as Man: A Course of Study (MACOS), inquiry-based learning, co-curriculum activities, and standards movements, adapted to fit this Southeastern locale, at a time when schools were struggling to desegregate. Local curriculum documents written in the 1970s reveal a traditional social studies curriculum. By the 1980s, APS\u27s social studies curriculum guides broadened to include a stronger focus on an enacted community—inside the classroom and around the world. In oral history interviews, however, former teachers, students, and school officials presented contrasting perspectives of how the social studies curriculum played out in the reality of Atlanta\u27s public schools during the desegregation era

    Millennials in the Workplace: A Communication Perspective on Millennials’ Organizational Relationships and Performance

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    Stereotypes about Millennials, born between 1979 and 1994, depict them as self-centered, unmotivated, disrespectful, and disloyal, contributing to widespread concern about how communication with Millennials will affect organizations and how they will develop relationships with other organizational members. We review these purported characteristics, as well as Millennials’ more positive qualities—they work well in teams, are motivated to have an impact on their organizations, favor open and frequent communication with their supervisors, and are at ease with communication technologies. We discuss Millennials’ communicated values and expectations and their potential effect on coworkers, as well as how workplace interaction may change Millennials
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