We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All ...subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.
We investigate the inner regions of the Milky Way using data from APOGEE and
Gaia
EDR3. Our inner Galactic sample has more than 26 500 stars within |
X
Gal
|< 5 kpc, |
Y
Gal
|< 3.5 kpc, |
Z
Gal
|< 1 ...kpc, and we also carry out the analysis for a foreground-cleaned subsample of 8000 stars that is more representative of the bulge–bar populations. These samples allow us to build chemo-dynamical maps of the stellar populations with vastly improved detail. The inner Galaxy shows an apparent chemical bimodality in key abundance ratios
α
/Fe, C/N, and Mn/O, which probe different enrichment timescales, suggesting a star formation gap (quenching) between the high- and low-
α
populations. Using a joint analysis of the distributions of kinematics, metallicities, mean orbital radius, and chemical abundances, we can characterize the different populations coexisting in the innermost regions of the Galaxy for the first time. The chemo-kinematic data dissected on an eccentricity–|
Z
|
max
plane reveal the chemical and kinematic signatures of the bar, the thin inner disc, and an inner thick disc, and a broad metallicity population with large velocity dispersion indicative of a pressure-supported component. The interplay between these different populations is mapped onto the different metallicity distributions seen in the eccentricity–|
Z
|
max
diagram consistently with the mean orbital radius and
V
ϕ
distributions. A clear metallicity gradient as a function of |
Z
|
max
is also found, which is consistent with the spatial overlapping of different populations. Additionally, we find and chemically and kinematically characterize a group of counter-rotating stars that could be the result of a gas-rich merger event or just the result of clumpy star formation during the earliest phases of the early disc that migrated into the bulge. Finally, based on 6D information, we assign stars a probability value of being on a bar orbit and find that most of the stars with large bar orbit probabilities come from the innermost 3 kpc, with a broad dispersion of metallicity. Even stars with a high probability of belonging to the bar show chemical bimodality in the
α
/Fe versus Fe/H diagram. This suggests bar trapping to be an efficient mechanism, explaining why stars on bar orbits do not show a significant, distinct chemical abundance ratio signature.
The molecular mechanisms underlying the response to exercise and inactivity are not fully understood. We propose an innovative approach to profile the skeletal muscle transcriptome to exercise and ...inactivity using 66 published datasets. Data collected from human studies of aerobic and resistance exercise, including acute and chronic exercise training, were integrated using meta-analysis methods (www.metamex.eu). Here we use gene ontology and pathway analyses to reveal selective pathways activated by inactivity, aerobic versus resistance and acute versus chronic exercise training. We identify NR4A3 as one of the most exercise- and inactivity-responsive genes, and establish a role for this nuclear receptor in mediating the metabolic responses to exercise-like stimuli in vitro. The meta-analysis (MetaMEx) also highlights the differential response to exercise in individuals with metabolic impairments. MetaMEx provides the most extensive dataset of skeletal muscle transcriptional responses to different modes of exercise and an online interface to readily interrogate the database.
We interact daily with computers that appear and behave like humans. Some researchers propose that people apply the same social norms to computers as they do to humans, suggesting that social ...psychological knowledge can be applied to our interactions with computers. In contrast, theories of human-automation interaction postulate that humans respond to machines in unique and specific ways. We believe that anthropomorphism-the degree to which an agent exhibits human characteristics-is the critical variable that may resolve this apparent contradiction across the formation, violation, and repair stages of trust. Three experiments were designed to examine these opposing viewpoints by varying the appearance and behavior of automated agents. Participants received advice that deteriorated gradually in reliability from a computer, avatar, or human agent. Our results showed (a) that anthropomorphic agents were associated with greater trust resilience, a higher resistance to breakdowns in trust; (b) that these effects were magnified by greater uncertainty; and c) that incorporating human-like trust repair behavior largely erased differences between the agents. Automation anthropomorphism is therefore a critical variable that should be carefully incorporated into any general theory of human-agent trust as well as novel automation design.
We present a sample of low-resolution 5-38 km Spitzer IRS spectra of the inner few square kiloparsecs of 59 nearby galaxies spanning a large range of star formation properties. A robust method for ...decomposing mid-infrared galaxy spectra is described and used to explore the behavior of PAH emission and the prevalence of silicate dust extinction. Evidence for silicate extinction is found in6 of the sample, at strengths that indicate that most normal galaxies undergo A sub(V) 3 mag averaged over then-centers. The contribution of PAH emission to the total infrared power is found to peak near 10% and extend up to 620% and is suppressed at metallicities Z Z /4, as well as in low-luminosity AGN environments. Strong interband PAH feature strength variations (2-5 times) are observed, with the presence of a weak AGN and, to a lesser degree, increasing metallicity shifting power to the longer wavelength bands. A peculiar PAH emission spectrum with markedly diminished 5-8 km features arises among the sample solely in systems with relatively hard radiation fields harboring low-luminosity AGNs. The AGNs may modify the emitting grain distribution and provide the direct excitation source of the unusual PAH emission, which cautions against using absolute PAH strength to estimate star formation rates in systems harboring active nuclei. Alternatively, the low star formation intensity often associated with weak AGNs may affect the spectrum. The effect of variations in the mid-infrared spectrum on broadband infrared surveys is modeled and points to more than a factor of 2 uncertainty in results that assume a fixed PAH emission spectrum, for redshifts z = 0-2.5.
Delirium, a prevalent organ dysfunction in critically ill patients, is independently associated with increased morbidity. This last decade has witnessed an exponential growth in delirium research in ...hospitalized patients, including those critically ill, and this research has highlighted that delirium needs to be better understood mechanistically to help foster research that will ultimately lead to its prevention and treatment. In this invited, evidence-based paper, a multinational and interprofessional group of clinicians and researchers from within the fields of critical care medicine, psychiatry, pediatrics, anesthesiology, geriatrics, surgery, neurology, nursing, pharmacy, and the neurosciences sought to address five questions: (1) What is the current standard of care in managing ICU delirium? (2) What have been the major recent advances in delirium research and care? (3) What are the common delirium beliefs that have been challenged by recent trials? (4) What are the remaining areas of uncertainty in delirium research? (5) What are some of the top study areas/trials to be done in the next 10 years? Herein, we briefly review the epidemiology of delirium, the current best practices for management of critically ill patients at risk for delirium or experiencing delirium, identify recent advances in our understanding of delirium as well as gaps in knowledge, and discuss research opportunities and barriers to implementation, with the goal of promoting an integrated research agenda.
This paper describes a soil moisture data set from the 82,000 km2 Murrumbidgee River Catchment in southern New South Wales, Australia. Data have been archived from the Murrumbidgee Soil Moisture ...Monitoring Network (MSMMN) since its inception in September 2001. The Murrumbidgee Catchment represents a range of conditions typical of much of temperate Australia, with climate ranging from semiarid to humid and land use including dry land and irrigated agriculture, remnant native vegetation, and urban areas. There are a total of 38 soil moisture‐monitoring sites across the Murrumbidgee Catchment, with a concentration of sites in three subareas. The data set is composed of 0–5 (or 0–8), 0–30, 30–60, and 60–90 cm average soil moisture, soil temperature, precipitation, and other land surface model forcing at all sites, together with other ancillary data. These data are available on the World Wide Web at http://www.oznet.org.au.
Key Points
Soil moisture data set from 82,000 square km Murrumbidgee Catchment, Australia
Data from 2001 and ongoing at 38 soil moisture monitoring sites
Sub‐hourly data at 4 depths for each site available at http://www.oznet.org.au
Rat L6, mouse C2C12, and primary human skeletal muscle cells (HSMCs) are commonly used to study biological processes in skeletal muscle, and experimental data on these models are abundant. However, ...consistently matched experimental data are scarce, and comparisons between the different cell types and adult tissue are problematic. We hypothesized that metabolic differences between these cellular models may be reflected at the mRNA level. Publicly available data sets were used to profile mRNA levels in myotubes and skeletal muscle tissues. L6, C2C12, and HSMC myotubes were assessed for proliferation, glucose uptake, glycogen synthesis, mitochondrial activity, and substrate oxidation, as well as the response to in vitro contraction. Transcriptomic profiling revealed that mRNA of genes coding for actin and myosin was enriched in C2C12, whereas L6 myotubes had the highest levels of genes encoding glucose transporters and the five complexes of the mitochondrial electron transport chain. Consistently, insulin-stimulated glucose uptake and oxidative capacity were greatest in L6 myotubes. Insulin-induced glycogen synthesis was highest in HSMCs, but C2C12 myotubes had higher baseline glucose oxidation. All models responded to electrical pulse stimulation-induced glucose uptake and gene expression but in a slightly different manner. Our analysis reveals a great degree of heterogeneity in the transcriptomic and metabolic profiles of L6, C2C12, or primary human myotubes. Based on these distinct signatures, we provide recommendations for the appropriate use of these models depending on scientific hypotheses and biological relevance.
Pandemics and subsequent lifestyle restrictions such as ‘lockdowns’ may have unintended consequences, including alterations in body weight. This systematic review assesses the impact of pandemic ...confinement on body weight and identifies contributory factors. A comprehensive literature search was performed in seven electronic databases and in grey sources from their inception until 1 July 2020 with an update in PubMed and Scopus on 1 February 2021. In total, 2361 unique records were retrieved, of which forty-one studies were identified eligible: one case–control study, fourteen cohort and twenty-six cross-sectional studies (469, 362 total participants). The participants ranged in age from 6 to 86 years. The proportion of female participants ranged from 37 % to 100 %. Pandemic confinements were associated with weight gain in 7·2–72·4 % of participants and weight loss in 11·1–32·0 % of participants. Weight gain ranged from 0·6 (sd 1·3) to 3·0 (sd 2·4) kg, and weight loss ranged from 2·0 (sd 1·4) to 2·9 (sd 1·5) kg. Weight gain occurred predominantly in participants who were already overweight or obese. Associated factors included increased consumption of unhealthy food with changes in physical activity and altered sleep patterns. Weight loss during the pandemic was observed in individuals with previous low weight, and those who ate less and were more physically active before lockdown. Maintaining a stable weight was more difficult in populations with reduced income, particularly in individuals with lower educational attainment. The findings of this systematic review highlight the short-term effects of pandemic confinements.
The 9th Banff Conference on Allograft Pathology was held in La Coruna, Spain on June 23–29, 2007. A total of 235 pathologists, clinicians and scientists met to address unsolved issues in ...transplantation and adapt the Banff schema for renal allograft rejection in response to emerging data and technologies. The outcome of the consensus discussions on renal pathology is provided in this article. Major updates from the 2007 Banff Conference were: inclusion of peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection, application of the Banff criteria to zero‐time and protocol biopsies and introduction of a new scoring for total interstitial inflammation (ti‐score). In addition, emerging research data led to the establishment of collaborative working groups addressing issues like isolated ‘v’ lesion and incorporation of omics‐technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.
The Ninth Banff Conference on Allograft Pathology held in La Coruna, Spain June 23‐29, 2007 resulted in new developments pertaining to C4d staining, peritubular capillaritis, protocol biopsies, lesion scoring, and eventual incorporation of “omics” technologies into kidney transplant rejection diagnosis.
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