We present initial results from a new high-contrast imaging program dedicated to stars that exhibit long-term Doppler radial velocity accelerations (or "trends"). The goal of the TRENDS (TaRgetting ...bENchmark-objects with Doppler Spectroscopy) imaging survey is to directly detect and study the companions responsible for accelerating their host star. In this first paper of the series, we report the discovery of low-mass stellar companions orbiting HD 53665, HD 68017, and HD 71881 using NIRC2 adaptive optics (AO) observations at Keck. Follow-up imaging demonstrates association through common proper motion. These comoving companions have red colors with estimated spectral types of K7-M0, M5, and M3-M4, respectively. We determine a firm lower limit to their mass from Doppler and astrometric measurements. In the near future, it will be possible to construct three-dimensional orbits and calculate the dynamical mass of HD 68017 B and possibly HD 71881 B. We already detect astrometric orbital motion of HD 68017 B, which has a projected separation of 13.0 AU. Each companion is amenable to AO-assisted direct spectroscopy. Further, each companion orbits a solar-type star, making it possible to infer metallicity and age from the primary. Such benchmark objects are essential for testing theoretical models of cool dwarf atmospheres.
Abstract Objective We primarily sought to evaluate home care nurses’ knowledge of evidence-based education topics in managing heart failure (HF). Moreover, we wanted to determine if differences were ...evident in nurses’ knowledge based on education and work experience, and to identify home care nurses’ specific educational needs. Methods A cross-sectional survey design was used. Home care nurses (n = 94) were recruited from 4 home care agencies. A previously published 20-item HF knowledge questionnaire was administered to participants, and an open-ended question determined participants’ need for further HF-related education. Results Home care nurses’ scores demonstrated a 78.9% knowledge level in overall HF education principles. The mean HF knowledge score was 15.78 (SD, ±1.69) out of a possible 20 points. Nurses scored lowest on knowledge related to asymptomatic hypotension (24.5% answered correctly), daily weight monitoring (26.6% answered correctly), and transient dizziness (30.9% answered correctly). Nurses requested further information on all HF topics addressed in the survey as well as on psychosocial issues, research evidence, and more information from other healthcare providers. Conclusion Our findings suggest that home care nurses may not be sufficiently knowledgeable in evidence-based education topics for managing HF. The results help confirm the need to develop educational programs for home care nurses in managing HF, which may lead to improved quality of patient education. Further research is needed to address specific deficits in the knowledge of home care nurses, and to determine if HF educational programs for nurses would enhance and sustain nurses’ knowledge of HF management education.
Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory ...syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.
The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.
Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use ...in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation.
Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival.
Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval CI, 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit.
We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00412360.).
Sirtuin 1 (Sirt1) is a NAD+-dependent deacetylase capable of countering age-related neurodegeneration, but the basis of Sirt1 neuroprotection remains elusive. Spinocerebellar ataxia type 7 (SCA7) is ...an inherited CAG-polyglutamine repeat disorder. Transcriptome analysis of SCA7 mice revealed downregulation of calcium flux genes accompanied by abnormal calcium-dependent cerebellar membrane excitability. Transcription-factor binding-site analysis of downregulated genes yielded Sirt1 target sites, and we observed reduced Sirt1 activity in the SCA7 mouse cerebellum with NAD+ depletion. SCA7 patients displayed increased poly(ADP-ribose) in cerebellar neurons, supporting poly(ADP-ribose) polymerase-1 upregulation. We crossed Sirt1-overexpressing mice with SCA7 mice and noted rescue of neurodegeneration and calcium flux defects. NAD+ repletion via nicotinamide riboside ameliorated disease phenotypes in SCA7 mice and patient stem cell-derived neurons. Sirt1 thus achieves neuroprotection by promoting calcium regulation, and NAD+ dysregulation underlies Sirt1 dysfunction in SCA7, indicating that cerebellar ataxias exhibit altered calcium homeostasis because of metabolic dysregulation, suggesting shared therapy targets.
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•Transcriptomes of SCA7 mice revealed downregulation of genes controlling Ca2+ flux•Altered membrane excitability in SCA7 involves NAD+ depletion and PARP1 activation•Increased Sirt1 rescued cerebellar degeneration and calcium defects in SCA7 mice•NAD+ repletion prevented disease in SCA7 mice and patient stem cell-derived neurons
How does Sirtuin-1 achieve neuroprotection? By studying SCA7, an inherited cerebellar degenerative disorder, Stoyas et al. discover that Sirtuin-1 mediates transcriptional activation of calcium regulatory genes in a NAD-dependent fashion, revealing a number of shared therapy targets for cerebellar ataxia.
Minimal residual disease (MRD) before myeloablative hematopoietic cell transplantation (HCT) is associated with adverse outcome in acute myeloid leukemia (AML) in first complete remission (CR1). To ...compare this association with that for patients in second complete remission (CR2) and to examine the quantitative impact of MRD, we studied 253 consecutive patients receiving myeloablative HCT for AML in CR1 (n = 183) or CR2 (n = 70) who had pre-HCT marrow aspirates analyzed by 10-color flow cytometry. Three-year estimates of overall survival were 73% (64%-79%) and 32% (17%-48%) for MRDneg and MRDpos CR1 patients, respectively, and 73% (57%-83%) and 44% (21%-65%) for MRDneg and MRDpos CR2 patients, respectively. Similar estimates of relapse were 21% (14%-28%) and 58% (41%-72%) for MRDneg and MRDpos CR1 patients, respectively, and 19% (9%-31%) and 68% (41%-85%) for MRDneg and MRDpos CR2 patients, respectively. Among the MRDpos patients, there was no statistically significant evidence that increasing levels of MRD were associated with increasing risks of relapse and death. After multivariable adjustment, risks of death and relapse were 2.61 times and 4.90 times higher for MRDpos patients (P < .001). Together, our findings indicate that the negative impact of pre-HCT MRD is similar for AML in CR1 and CR2 with even minute levels (≤0.1%) as being associated with adverse outcome.
•The negative impact of pre-HCT flow cytometrically determined MRD is similar for AML in CR1 and CR2.•Even minute levels of MRD (≤0.1%) are associated with adverse outcome.
Effectiveness of double umbilical cord blood (dUCB) grafts relative to conventional marrow and mobilized peripheral blood from related and unrelated donors has yet to be established. We studied 536 ...patients at the Fred Hutchinson Cancer Research Center and University of Minnesota with malignant disease who underwent transplantation with an human leukocyte antigen (HLA)–matched related donor (MRD, n = 204), HLA allele–matched unrelated donor (MUD, n = 152) or 1-antigen–mismatched unrelated adult donor (MMUD, n = 52) or 4-6/6 HLA matched dUCB (n = 128) graft after myeloablative conditioning. Leukemia-free survival at 5 years was similar for each donor type (dUCB 51% 95% confidence interval (CI), 41%-59%; MRD 33% 95% CI, 26%-41%; MUD 48% 40%-56%; MMUD 38% 95% CI, 25%-51%). The risk of relapse was lower in recipients of dUCB (15%, 95% CI, 9%-22%) compared with MRD (43%, 95% CI, 35%-52%), MUD (37%, 95% CI, 29%-46%) and MMUD (35%, 95% CI, 21%-48%), yet nonrelapse mortality was higher for dUCB (34%, 95% CI, 25%-42%), MRD (24% (95% CI, 17%-39%), and MUD (14%, 95% CI, 9%-20%). We conclude that leukemia-free survival after dUCB transplantation is comparable with that observed after MRD and MUD transplantation. For patients without an available HLA matched donor, the use of 2 partially HLA-matched UCB units is a suitable alternative.
Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected ...immune cell subsets may be associated with levels of systolic blood pressure (SBP).
We assayed immune cells from cryopreserved samples collected at the baseline examination (2000-2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level.
The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg 95% confidence interval (CI) 1.34-3.42 higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82-2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14
CD16
) was associated with 2.01 mmHG (95% CI 0.79-3.24) lower average systolic blood pressure. There were no associations of CD4
T helper cell subsets with average systolic blood pressure.
These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.
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