The conservation laws, such as those of charge, energy and momentum, have a central role in physics. In some special cases, classical conservation laws are broken at the quantum level by quantum ...fluctuations, in which case the theory is said to have quantum anomalies. One of the most prominent examples is the chiral anomaly, which involves massless chiral fermions. These particles have their spin, or internal angular momentum, aligned either parallel or antiparallel with their linear momentum, labelled as left and right chirality, respectively. In three spatial dimensions, the chiral anomaly is the breakdown (as a result of externally applied parallel electric and magnetic fields) of the classical conservation law that dictates that the number of massless fermions of each chirality are separately conserved. The current that measures the difference between left- and right-handed particles is called the axial current and is not conserved at the quantum level. In addition, an underlying curved space-time provides a distinct contribution to a chiral imbalance, an effect known as the mixed axial-gravitational anomaly, but this anomaly has yet to be confirmed experimentally. However, the presence of a mixed gauge-gravitational anomaly has recently been tied to thermoelectrical transport in a magnetic field, even in flat space-time, suggesting that such types of mixed anomaly could be experimentally probed in condensed matter systems known as Weyl semimetals. Here, using a temperature gradient, we observe experimentally a positive magneto-thermoelectric conductance in the Weyl semimetal niobium phosphide (NbP) for collinear temperature gradients and magnetic fields that vanishes in the ultra-quantum limit, when only a single Landau level is occupied. This observation is consistent with the presence of a mixed axial-gravitational anomaly, providing clear evidence for a theoretical concept that has so far eluded experimental detection.
•These updated ESMO Clinical Practice Guidelines provide key recommendations on the management of chronic lymphocytic leukaemia (CLL)•Authorship includes a multidisciplinary group of experts from ...different institutions and countries in Europe•Recommendations are provided, including levels of evidence and grades of recommendation where applicable•Prognosis and treatment decisions in CLL depend on genetic and clinical factors including age, stage and comorbidities•Therapies targeting B-cell receptor pathway or defect mechanism of apoptosis induce long lasting remissions
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a ...particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i.e., inhibitors of B-cell receptor (BcR) signaling and anti-apoptotic BCL2 family members, owing to their efficacy in patients with TP53 defects. In this report, the TP53 Network of the European Research Initiative on Chronic Lymphocytic Leukemia (ERIC) presents updated recommendations on the methodological approaches for TP53 mutation analysis. Moreover, it provides guidance to ensure that the analysis is performed in a timely manner for all patients requiring treatment and that the data is interpreted and reported in a consistent, standardized, and accurate way. Since next-generation sequencing technologies are gaining prominence within diagnostic laboratories, this report also offers advice and recommendations for the interpretation of TP53 mutation data generated by this methodology.
Highlights • Motor fitness was positively related to basal ganglia volume in older adults. • Basal ganglia volume moderated association of motor fitness and executive control. • 12-month coordination ...training increased volume of the caudate and globus pallidus.
Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells ...are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide (
H) in vivo labeling method in which patients consumed deuterated (heavy) water (
H
O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4
CD5
phenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.
Both acute and chronic kidney disease are common after liver transplantation and result in significant morbidity and mortality. The introduction of the Model for End‐stage Liver Disease score has ...directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver–kidney transplantations performed. Kidney dysfunction in this population is typically multifactorial and related to preexisting conditions, pretransplantation renal injury, perioperative events, and posttransplantation nephrotoxic immunosuppressive therapies. The management of kidney disease after liver transplantation is challenging, as by the time the serum creatinine level is significantly elevated, few interventions affect the course of progression. Also, immunological factors such as antibody‐mediated kidney rejection have become of greater interest given the rising liver–kidney transplant population. Therefore, this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestine Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver–kidney transplantation. Key points and practice‐based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
This review summarizes key data and provides practice‐based guidelines to assess and preserve renal function early and late after liver and liver–kidney transplantation. See page 2516 for the companion review.
The skin epithelium undergoes constant renewal, a process that is driven by stem cells (SCs) localising to the interfollicular epidermis and different regions of the hair follicle. Over the last ...years, tremendous progress has been made to unravel the physiological function of distinct stem and progenitor cell populations by using genetic lineage tracing in vivo, transplantation, clonogenicity approaches and live cell imaging. It turned out that these cell compartments constitute heterogeneous SC pools and that individual SCs respond differently to various signals sent by the microenvironment. Recent genetic manipulation experiments and elegant mouse models have shed light on the signalling pathways being crucial for self-renewal and lineage fate decisions during tissue homeostasis. Here, we summarise current concepts of SC function in mammalian skin and focus on the dynamic behaviour of SCs during morphogenesis and tissue regeneration of the skin epithelium. Clearly, understanding the cellular and molecular mechanisms of SC regulation and function during tissue homeostasis has enormous impact on our view of the pathogenesis of various skin diseases and will be beneficial for regenerative medicine. Recent experiments suggest an important role of tissue SCs in the process of skin tumour initiation and progression. For the future, the genuine challenge is to further dissect SC function in pathophysiological settings and to translate our knowledge to design novel efficient therapeutic strategies for treatment of cutaneous cancer.
We report the first measurements of the formation and structure of a magnetized collisionless shock by a laser‐driven magnetic piston in a current‐free laboratory plasma. This new class of ...experiments combines a high‐energy laser system and a large magnetized plasma to transfer energy from a laser plasma plume to the ambient ions through collisionless coupling, until a self‐sustained MA∼ 2 magnetosonic shock separates from the piston. The ambient plasma is highly magnetized, current free, and large enough (17 m × 0.6 m) to support Alfvén waves. Magnetic field measurements of the structure and evolution of the shock are consistent with two‐dimensional hybrid simulations, which show Larmor coupling between the debris and ambient ions and the presence of reflected ions, which provide the dissipation. The measured shock formation time confirms predictions from computational work.
Key Points
First laboratory observation of collisionless shocks of cosmic relevanceFirst measurement of shock formation timeMeasured upper bound of debris‐ambient coupling criterion
Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute ...lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average increase in ALC was 66%, and in>40% of patients the ALC peaked within 24 h of initiating treatment. Circulating CLL cells on day 2 showed increased Ki67 and CD38 expression, indicating an efflux of tumor cells from the tissue compartments into the blood. The kinetics and degree of the treatment-induced lymphocytosis was highly variable; interestingly, in patients with a high baseline ALC the relative increase was mild and resolution rapid. After two cycles of treatment the disease burden in the LN, bone marrow and spleen decreased irrespective of the relative change in ALC. Whole-blood viscosity was dependent on both ALC and hemoglobin. No adverse events were attributed to the lymphocytosis.
Over the last decade the age of liver transplant (LT) recipients and the likelihood of coronary artery disease (CAD) in this population have increased. There are no multicenter studies that have ...examined the impact of CAD on LT outcomes. In this historical cohort study, we identified adult LT recipients who underwent angiography prior to transplantation at seven institutions over a 12‐year period. For each patient we recorded demographic data, recipient and donor risk factors, duration of follow‐up, the presence of angiographically proven obstructive CAD (≥50% stenosis) and post‐LT survival. Obstructive CAD was present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in 479 patients, the CAD(−) group. Patient survival was similar for the CAD(+) group (adjusted HR 1.13, CI = 0.79, 1.62, p = 0.493) compared to the CAD(−) group. The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n = 96), and moderate CAD (CADmod, 50–70% stenosis, n = 55) groups. Survival for the CADsev (adjusted HR = 1.26, CI = 0.83, 1.91, p = 0.277) and CADmod (adjusted HR = 0.93, CI = 0.52, 1.66, p = 0.797) groups were similar to the CAD(−) group. We conclude that when current CAD treatment strategies are employed prior to transplant, post‐LT survival is not significantly different between patients with and without obstructive CAD.
The authors find no significant difference in post‐liver transplant survival between patients with and without angiographically proven obstructive coronary artery disease when current treatment regimens are employed.
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