Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that ...reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.
A multidisciplinary panel of experts from AST reviews the literature regarding the use of organs from donors who test positive for hepatitis B virus, and provides recommendations for their use in liver, kidney, heart, and lung transplant recipients.
Cse4 is the budding yeast homologue of CENP-A, a modified histone H3 that specifies the base of kinetochores in all eukaryotes. Budding yeast is unique in having only one kinetochore microtubule ...attachment site per centromere. The centromere is specified by CEN DNA, a sequence-specific binding complex (CBF3), and a Cse4-containing nucleosome. Here we compare the ratio of kinetochore proximal Cse4-GFP fluorescence at anaphase to several standards including purified EGFP molecules in vitro to generate a calibration curve for the copy number of GFP-fusion proteins. Our results yield a mean of ~5 Cse4s, ~3 inner kinetochore CBF3 complexes, and ~20 outer kinetochore Ndc80 complexes. Our calibrated measurements increase 2.5-3-fold protein copy numbers at eukaryotic kinetochores based on previous ratio measurements assuming two Cse4s per budding yeast kinetochore. All approximately five Cse4s may be associated with the CEN nucleosome, but we show that a mean of three Cse4s could be located within flanking nucleosomes at random sites that differ between chromosomes.
We estimate a production function model of aggregate economic growth including two variables that microeconomists have identified as fundamental components of human capital: work experience and ...health. Our main result is that good health has a positive, sizable, and statistically significant effect on aggregate output even when we control for experience of the workforce. We argue that the life expectancy effect in growth regressions appears to be a real labor productivity effect, and is not the result of life expectancy acting as a proxy for worker experience.
The Fermi-LAT experiment recently reported high precision measurements of the spectrum of cosmic-ray electrons-plus-positrons (CRE) between 20
GeV and 1
TeV. The spectrum shows no prominent spectral ...features, and is significantly harder than that inferred from several previous experiments. Here we discuss several interpretations of the Fermi results based either on a single large scale Galactic CRE component or by invoking additional electron–positron primary sources, e.g. nearby pulsars or particle dark matter annihilation. We show that while the reported Fermi-LAT data alone can be interpreted in terms of a single component scenario, when combined with other complementary experimental results, specifically the CRE spectrum measured by H.E.S.S. and especially the positron fraction reported by PAMELA between 1 and 100
GeV, that class of models fails to provide a consistent interpretation. Rather, we find that several combinations of parameters, involving both the pulsar and dark matter scenarios, allow a consistent description of those results. We also briefly discuss the possibility of discriminating between the pulsar and dark matter interpretations by looking for a possible anisotropy in the CRE flux.
Information regarding treatment of post‐transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab ...and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirty‐five patients met inclusion criteria. Twenty‐two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein‐Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty‐three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twenty‐six percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV‐positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV‐negative tumors or need a rapid response.
Generation of motile force is one of the main functions of the eukaryotic kinetochore during cell division. In recent years, the KMN network of proteins (Ndc80 complex, Mis12 complex, and KNL-1 ...complex) has emerged as a highly conserved core microtubule-binding complex at the kinetochore. It plays a major role in coupling force generation to microtubule plus-end polymerization and depolymerization. In this review, we discuss current theoretical mechanisms of force generation, and then focus on emerging information about mechanistic contributions from the Ndc80 complex in eukaryotes and the microtubule-binding Dam1/DASH complex from fungi. New information has also become available from super-resolution light microscopy on the protein architecture of the kinetochore-microtubule attachment site in both budding yeast and humans, which provides further insight into the mechanism of force generation. We briefly discuss potential contributions of motors, other microtubule-associated proteins, and microtubule depolymerases. Using the above evidence, we present speculative models of force generation at the kinetochore.
While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population ...remains unclear. We performed a prospective 2‐arm trial utilizing an EBV PCR panel measuring LMP‐1, EBER‐1 and EBNA‐1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD. In Arm A, 1/31 (3%) patients developed a transient plasma EBV load. Thirteen of 31 (42%) had detectable intracellular EBV. In Arm B, 17 (49%) patients were diagnosed with PTLD. Thirteen (76%) had EBV‐positive PTLD with 12/13 (92%) having detectable EBV by PCR. The EBV PCR panel had a high sensitivity (92%), specificity (72%), positive predictive value (PPV) (71%) and negative predictive value (NPV) (93%) for diagnosing EBV‐positive PTLD and followed patients' clinical course well (p < 0.001). Comparing the individual PCR assays, plasma EBNA PCR was superior with high sensitivity (77%), specificity (100%), PPV (100%) and NPV (86%). We conclude that EBV PCR is a useful test for managing PTLD patients. While plasma EBNA PCR is the best single assay for diagnosing and monitoring PTLD, the complete PCR panel is superior for ruling out its presence.
This study determined that utilizing plasma as a specimen source and gene targets EBNA and EBER in EBV quantitative real‐time PCR assays provided the highest sensitivity and specificity for diagnosing and monitoring PTLD. Therefore an assay that incorporates both gene targets would be the most successful in the management of PTLD patients.
Context. The nearby Large Magellanic Cloud (LMC) provides a rare opportunity of a spatially resolved view of an external star-forming galaxy in γ-rays. The LMC was detected at 0.1–100 GeV as an ...extended source with CGRO/EGRET and using early observations with the Fermi-LAT. The emission was found to correlate with massive star-forming regions and to be particularly bright towards 30 Doradus. Aims. Studies of the origin and transport of cosmic rays (CRs) in the Milky Way are frequently hampered by line-of-sight confusion and poor distance determination. The LMC offers a complementary way to address these questions by revealing whether and how the γ-ray emission is connected to specific objects, populations of objects, and structures in the galaxy. Methods. We revisited the γ-ray emission from the LMC using about 73 months of Fermi-LAT P7REP data in the 0.2–100 GeV range. We developed a complete spatial and spectral model of the LMC emission, for which we tested several approaches: a simple geometrical description, template-fitting, and a physically driven model for CR-induced interstellar emission. Results. In addition to identifying PSR J0540−6919 through its pulsations, we find two hard sources positionally coincident with plerion N 157B and supernova remnant N 132D, which were also detected at TeV energies with H.E.S.S. We detect an additional soft source that is currently unidentified. Extended emission dominates the total flux from the LMC. It consists of an extended component of about the size of the galaxy and additional emission from three to four regions with degree-scale sizes. If it is interpreted as CRs interacting with interstellar gas, the large-scale emission implies a large-scale population of ~1–100 GeV CRs with a density of ~30% of the local Galactic value. On top of that, the three to four small-scale emission regions would correspond to enhancements of the CR density by factors 2 to 6 or higher, possibly more energetic and younger populations of CRs compared to the large-scale population. An alternative explanation is that this is emission from an unresolved population of at least two dozen objects, such as pulsars and their nebulae or supernova remnants. This small-scale extended emission has a spatial distribution that does not clearly correlate with known components of the LMC, except for a possible relation to cavities and supergiant shells. Conclusions. The Fermi-LAT GeV observations allowed us to detect individual sources in the LMC. Three of the newly discovered sources are associated with rare and extreme objects. The 30 Doradus region is prominent in GeV γ-rays because PSR J0540−6919 and N 157B are strong emitters. The extended emission from the galaxy has an unexpected spatial distribution, and observations at higher energies and in radio may help to clarify its origin.
We present broadband (radio, optical, and X-ray) light curves and spectra of the afterglows of four long-duration gamma-ray bursts (GRBs; GRBs 09032,09032,090902B, and 090926A) detected by the ...Gamma-Ray Burst Monitor and Large Area Telescope (LAT) instruments on the Fermi satellite. With its wide spectral bandpass, extending to GeV energies, Fermi is sensitive to GRBs with very large isotropic energy releases (1054 erg). Although rare, these events are particularly important for testing GRB central-engine models. When combined with spectroscopic redshifts, our afterglow data for these four events are able to constrain jet collimation angles, the density structure of the circumburst medium, and both the true radiated energy release and the kinetic energy of the outflows. In agreement with our earlier work, we find that the relativistic energy budget of at least one of these events (GRB 090926A) exceeds the canonical value of 1051 erg by an order of magnitude. Such energies pose a severe challenge for models in which the GRB is powered by a magnetar or a neutrino-driven collapsar, but remain compatible with theoretical expectations for magnetohydrodynamical collapsar models (e.g., the Blandford-Znajek mechanism). Our jet opening angles ( Delta *c) are similar to those found for pre-Fermi GRBs, but the large initial Lorentz factors ( Delta *G0) inferred from the detection of GeV photons imply Delta *c Delta *G0 70-90, values which are above those predicted in magnetohydrodynamic models of jet acceleration. Finally, we find that these Fermi-LAT events preferentially occur in a low-density circumburst environment, and we speculate that this might result from the lower mass-loss rates of their lower-metallicity progenitor stars. Future studies of Fermi-LAT afterglows at radio wavelengths with the order-of-magnitude improvement in sensitivity offered by the Extended Very Large Array should definitively establish the relativistic energy budgets of these events.
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