IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological ...appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.
We investigate the search prospects for new scalars beyond the standard model at the large hadron collider (LHC). In these studies two real scalars
S
and
χ
have been introduced in a two Higgs-doublet ...model (2HDM), where
S
is a portal to dark matter (DM) through its interaction with
χ
, a DM candidate and a possible source of missing transverse energy (
E
T
miss
). Previous studies focussed on a heavy scalar
H
decay mode
H
→
h
χ
χ
, which was studied using an effective theory in order to explain a distortion in the Higgs boson (
h
) transverse momentum spectrum (von Buddenbrock et al. in
arXiv:1506.00612
hep-ph,
2015
). In this work, the effective decay is understood more deeply by including a mediator
S
, and the focus is changed to
H
→
h
S
,
S
S
with
S
→
χ
χ
. Phenomenological signatures of all the new scalars in the proposed 2HDM are discussed in the energy regime of the LHC, and their mass bounds have been set accordingly. Additionally, we have performed several analyses with final states including leptons and
E
T
miss
, with
H
→
4
W
,
t
(
t
)
H
→
6
W
and
A
→
Z
H
channels, in order to understand the impact these scalars have on current searches.
Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to ...collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ54-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ’s AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP–complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.
•TBI conditioning for autotransplantation is associated with higher risks of t-MN.•Risks of t-MN after autotransplantation for NHL are increasing.•Autotransplantation increases risks of MDS more than ...AML.
Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
9028 recipients of hematopoietic cell autotransplants (1995–2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.
335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval 1.4, 11.6) and NHL (HR = 2.5 1.1, 2.5); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 1.3, 2.8); and (3) subjects with NHL transplanted in 2005–2010 versus 1995–1999 (HR = 2.1 1.5, 3.1). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5–10 times the background rate. In contrast, relative risks were 10–50 for AML and approximately 100 for MDS in the autotransplant cohort.
There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
We discuss how to obtain black hole quasinormal modes (QNMs) using the asymptotic iteration method (AIM), initially developed to solve second-order ordinary differential equations. We introduce the ...standard version of this method and present an improvement more suitable for numerical implementation. We demonstrate that the AIM can be used to find radial QNMs for Schwarzschild, Reissner-Nordström (RN), and Kerr black holes in a unified way. We discuss some advantages of the AIM over the continued fractions method (CFM). This paper presents for the first time the spin 0, 1/2 and 2 QNMs of a Kerr black hole and the gravitational and electromagnetic QNMs of the RN black hole calculated via the AIM and confirms results previously obtained using the CFM. We also present some new results comparing the AIM to the WKB method. Finally we emphasize that the AIM is well suited to higher-dimensional generalizations and we give an example of doubly rotating black holes.
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