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 report the first plausible optical electromagnetic counterpart to a (candidate) binary black hole merger. Detected by the Zwicky Transient Facility, the electromagnetic flare is consistent with ...expectations for a kicked binary black hole merger in the accretion disk of an active galactic nucleus B. McKernan, K. E. S. Ford, I. Bartoset al., Astrophys. J. Lett.884, L50 (2019) and is unlikely <O(0.01%)) due to intrinsic variability of this source. The lack of color evolution implies that it is not a supernova and instead is strongly suggestive of a constant temperature shock. Other false-positive events, such as microlensing ora tidal disruption event, are ruled out or constrained to be <O(0.1%). If the flare is associated withS190521g, we find plausible values of total mass M(BBH) ∼ 100 Mꙩ, kick velocity v(k) ∼ 200 km/s at θ ∼ 60° in a disk with aspect ratio H/a ∼ 0.01(i.e., disk height H at radius a) and gas density ρ ∼ 10^(−10)g/cu.cm. The merger could have occurred at a disk migration trap (a ∼ 700 r(g); r(g) ≡ GM(SMBH)/sq.c, where M(SMBH) is the mass of the active galactic nucleus supermassive black hole). The combination of parameters implies a significant spin for at least one of the black holes in S190521g. The timing of our spectroscopy prevents useful constraints on broad-line asymmetry due to an off-center flare. We predict a repeat flare in this source due to a reencountering with the disk in ∼ 1.6 yr(M(SMBH)/10^(8) Mꙩ)(a/10^(3)r(g))^(3/2).
Abstract
At the intersection of quantum theory and relativity lies the possibility of a clock experiencing a superposition of proper times. We consider quantum clocks constructed from the internal ...degrees of relativistic particles that move through curved spacetime. The probability that one clock reads a given proper time conditioned on another clock reading a different proper time is derived. From this conditional probability distribution, it is shown that when the center-of-mass of these clocks move in localized momentum wave packets they observe classical time dilation. We then illustrate a quantum correction to the time dilation observed by a clock moving in a superposition of localized momentum wave packets that has the potential to be observed in experiment. The Helstrom-Holevo lower bound is used to derive a proper time-energy/mass uncertainty relation.
Phylogenetic analysis aims to establish the true relationships between taxa. Different analytical methods, however, can reach different conclusions. In order to establish which approach best ...reconstructs true relationships, previous studies have simulated datasets from known tree topologies, and identified the method that reconstructs the generative tree most accurately. On this basis, researchers have argued that morphological datasets should be analysed by Bayesian approaches, which employ an explicit probabilistic model of evolution, rather than parsimony methods-with implied weights parsimony sometimes identified as particularly inaccurate. Accuracy alone, however, is an inadequate measure of a tree's utility: a fully unresolved tree is perfectly accurate, yet contains no phylogenetic information. The highly resolved trees recovered by implied weights parsimony in fact contain as much useful information as the more accurate, but less resolved, trees recovered by Bayesian methods. By collapsing poorly supported groups, this superior resolution can be traded for accuracy, resulting in trees as accurate as those obtained by a Bayesian approach. By contrast, equally weighted parsimony analysis produces trees that are less resolved and less accurate, leading to less reliable evolutionary conclusions.
Zika virus: history of a newly emerging arbovirus Wikan, Nitwara, PhD; Smith, Duncan R, Prof
Lancet. Infectious diseases/The Lancet. Infectious diseases,
07/2016, Volume:
16, Issue:
7
Journal Article
Peer reviewed
Open access
Summary Zika virus was originally identified in a sentinel rhesus monkey in the Zika Forest of Uganda in 1947. The virus is a member of the family Flaviviridae, genus Flavivirus , and is transmitted ...to humans by Aedes species mosquitoes. The first report of Zika virus outside Africa and Asia was in 2007 when the virus was associated with a small outbreak in Yap State, part of the Federated States of Micronesia. Since then, Zika virus infections have been reported around the world, including in southeast Asia; French Polynesia and other islands in the Pacific Ocean; and parts of South, Central, and North America. Symptomatic infection in human beings normally results in a mild and self-limiting febrile disease, although recent reports have suggested a possible association with more serious sequelae such as Guillain-Barré syndrome, and microcephaly in newborn infants of mothers infected with Zika virus during pregnancy. In this Review, we summarise the history of Zika virus from its first detection to its current worldwide distribution.
Land subsidence as a result of groundwater overpumping in the San Joaquin Valley, California, is associated with the loss of groundwater storage and aquifer contamination. Although the physical ...processes governing land subsidence are well understood, building predictive models of subsidence is challenging because so much subsurface information is required to do so accurately. For the first time, we integrate airborne electromagnetic data, representing the subsurface, with subsidence data, mapped by interferometric synthetic aperture radar (InSAR), to model deformation. By combining both data sets, we are able to solve for hydrologic and geophysical properties of the subsurface to effectively model the complex spatiotemporal process of deformation. The resulting model reveals that roughly 3 m of subsidence has occurred at one location of our study area from 1990 to 2018. This model also allows us to predict subsidence more accurately under future hydrologic scenarios, which is needed to develop plans for sustainable groundwater use.
Key Points
InSAR and AEM data are combined to produce accurate deformation models at three locations in the San Joaquin Valley of California
The model can be used to predict the impact of future droughts or managed aquifer recharge on land subsidence
The method of model development could be extended to much larger areas due to the ability to acquire both data sets rapidly
Depression is a common comorbidity in cancer cases, affecting >10% of patients. A cancer diagnosis is life-changing, and is a source of considerable psychological and emotional stress. ...Non-pathological sadness may be a normal response to a cancer diagnosis, however, stress beyond the coping mechanisms of patients may result in major depressive disorder. The current review, in addition to the obvious psychosocial elements of depression, explores its biological mechanisms, including tissue damage, inflammatory mediators and the chronic stress response, and how these immune and endocrine pathways may underlie depression in cancer. Possible iatrogenic causes of depression in cancer are also explored. There is a strong need to identify and treat depression in cancer patients in order to increase quality of life and reduce mortality. The most popular clinical and potential future biochemical screening tools for depression in cancer are briefly discussed. The interventions used will vary for every patient, but may include psychosocial therapies or pharmacotherapy; however, a paucity of research on the most effective management of depression in cancer means the optimal combination of therapies is unknown. Selection of antidepressants should be carefully considered, given the common side effects of chemotherapy (such as nausea), and the necessity to avoid serious interactions, including reducing the effectiveness of chemotherapeutic drugs. The possible link between the chronic stress response, which may predispose patients to depression, and the risk of mortality from cancer is also explored. The complex interactions between the endocrine, nervous and immune systems, which continue to be elucidated, may offer the opportunity for the development of more rapid and efficacious treatments for depression in cancer in the future.
Adolescent Undernutrition Christian, Parul; Smith, Emily R.
Annals of nutrition & metabolism,
01/2018, Volume:
72, Issue:
4
Journal Article
Peer reviewed
Open access
Background: Adolescents, comprised of 10–19 year olds, form the largest generation of young people in our history. There are an estimated 1.8 billion adolescents in the world, with 90% residing in ...low- and middle-income countries. The burden of disease among adolescents has its origins in infectious and injury-related causes, but nutritional deficiencies, suboptimal linear growth, and undernutrition are major public health problems, even as overweight may be on the rise in many contexts. Summary and Key Messages: Girls are most vulnerable to the influences of cultural and gender norms, which often discriminate against them. Dietary patterns and physical activity, in addition to schooling and countervailing social norms for early marriage, influence health and nutritional well-being of adolescents. Nutrient requirements – including those for energy, protein, iron, calcium, and others – increase in adolescence to support adequate growth and development. In settings where dietary intakes are suboptimal, anemia and micronutrient deficiencies are high. Endocrine factors are essential for promoting normal adolescent growth and are sensitive to undernutrition. Growth velocity increases during puberty when peak height velocity occurs and catch-up is possible; in girls, about 15–25% of adult height is attained. A premature pregnancy can halt linear growth and increase the risk of adverse birth outcomes. Research is needed to fill the huge data gaps related to nutrition and growth during adolescence, in addition to testing interventions during this second window of opportunity to enhance growth and development, improve human capital, and to end the intergenerational cycle of growth failure.
PDF
