•This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees.•This process incorporates advances in approaches in risk assessment used by RIFM ...over the past ten years.•A framework for choosing structural analogs and consideration of the Threshold of Toxicological Concern (TTC) are included.•Quantitative Risk Assessment (QRA) for dermal sensitization and aggregate exposure assessment methodologies are included.•The latest alternatives to animal testing methodology and environmental risk assessment are included.
The Research Institute for Fragrance Materials, Inc. (RIFM) has been engaged in the generation and evaluation of safety data for fragrance materials since its inception over 45 years ago. Over time, RIFM's approach to gathering data, estimating exposure and assessing safety has evolved as the tools for risk assessment evolved. This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years. These changes include incorporating 1) new scientific information including a framework for choosing structural analogs, 2) consideration of the Threshold of Toxicological Concern (TTC), 3) the Quantitative Risk Assessment (QRA) for dermal sensitization, 4) the respiratory route of exposure, 5) aggregate exposure assessment methodology, 6) the latest methodology and approaches to risk assessments, 7) the latest alternatives to animal testing methodology and 8) environmental risk assessment. The assessment begins with a thorough analysis of existing data followed by in silico analysis, identification of ‘read across’ analogs, generation of additional data through in vitro testing as well as consideration of the TTC approach. If necessary, risk management may be considered.
A
bstract
A comprehensive set of azimuthal single-spin and double-spin asymmetries in semi-inclusive leptoproduction of pions, charged kaons, protons, and antiprotons from transversely polarized ...protons is presented. These asymmetries include the previously published HERMES results on Collins and Sivers asymmetries, the analysis of which has been extended to include protons and antiprotons and also to an extraction in a three-dimensional kinematic binning and enlarged phase space. They are complemented by corresponding results for the remaining four single-spin and four double-spin asymmetries allowed in the one-photon-exchange approximation of the semi-inclusive deep-inelastic scattering process for target-polarization orientation perpendicular to the direction of the incoming lepton beam. Among those results, significant non-vanishing cos (
ϕ−ϕ
S
) modulations provide evidence for a sizable worm-gear (II) distribution,
g
1
T
q
x
p
T
2
. Most of the other modulations are found to be consistent with zero with the notable exception of large sin (
ϕ
S
) modulations for charged pions and
K
+
.
Summary
Background
In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in ...subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown.
Objectives
To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension.
Methods
Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well‐demarcated lesions. Samples were transparentized and subjected to whole‐mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two‐photon microscopy. The shape and location of the histological border were compared with those of the clinical border.
Results
In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema.
Conclusions
In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.
What's already known about this topic?
Paget cells in extramammary Paget disease often spread beyond the clinical border, which is referred to as subclinical extension.
The spreading pattern of the subclinically extended Paget cells remains unclear.
There are no reports on the macroscopic appearances of lesions accompanied by subclinical extension.
What does this study add?
Three‐dimensional analysis by whole‐mount immunostaining revealed two spreading patterns of Paget cells in subclinical extension.
Paget cells formed either small satellite lesions or continuous lesions forming a polygonal margin.
All subclinically extended Paget cells were detected outside hypopigmented patches with erythema.
Respond to this article
Linked Comment: Hatta. Br J Dermatol 2017; 177:18–19
Azimuthal single-spin asymmetries of leptoproduced pions and charged kaons were measured on a transversely polarized hydrogen target. Evidence for a naive-T-odd, transverse-momentum-dependent parton ...distribution function is deduced from nonvanishing Sivers effects for pi(+), pi(0), and K(+/-), as well as in the difference of the pi(+) and pi(-) cross sections.
A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The ...following kinematic domain is covered by the data: photon virtuality Q2>1 (GeV/c)2, invariant mass of the hadronic system W>5 GeV/c2, Bjorken scaling variable in the range 0.003<x<0.4, fraction of the virtual photon energy carried by the hadron in the range 0.2<z<0.8, and square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/c)2<PhT2<3 (GeV/c)2. The multiplicities are presented as a function of PhT2 in three-dimensional bins of x, Q2, z and compared to previous semi-inclusive measurements. We explore the small-PhT2 region, i.e. PhT2<1 (GeV/c)2, where hadron transverse momenta are expected to arise from nonperturbative effects, and also the domain of larger PhT2, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small PhT2 to study the dependence of the average transverse momentum ⟨PhT2⟩ on x, Q2 and z. The power-law behavior of the multiplicities at large PhT2 is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.
Summary
Docetaxel and paclitaxel are widely used in the treatment of various malignant neoplasms. Taxane‐induced sclerosis is dose‐dependent and usually not generalized. Little information on the ...pathogenesis of scleroderma is currently available. Here, we report a case of generalized scleroderma and a case of early‐stage oedematous sclerosis, both of which presented with intense versican deposits after administration of taxane for angiosarcoma.
What's already known about this topic?
Taxane‐induced sclerosis occurs dose dependently; however, little information on the pathogenesis of scleroderma is currently available.
What does this study add?
We analysed collagen type I, hyaluronan and versican, and revealed that administration of taxane increased the amount of versican, which led to oedema and sclerosis in our patients.
The COMPASS Collaboration at CERN has measured diffractive dissociation of 190 GeV/c pions into the π(-)π(-)π(+) final state using a stationary hydrogen target. A partial-wave analysis (PWA) was ...performed in bins of 3π mass and four-momentum transfer using the isobar model and the so far largest PWA model consisting of 88 waves. A narrow peak is observed in the f0(980)π channel with spin, parity and C-parity quantum numbers J(PC)=1(++). We present a resonance-model study of a subset of the spin-density matrix selecting 3π states with J(PC)=2(++) and 4(++) decaying into ρ(770)π and with J(PC)=1(++) decaying into f0(980)π. We identify a new a1 meson with mass (1414(-13)(+15)) MeV/c2 and width (153(-23)(+8)) MeV/c2. Within the final states investigated in our analysis, we observe the new a1(1420) decaying only into f0(980)π, suggesting its exotic nature.
Background Cholinergic urticaria (CU) has well‐described characteristic clinical presentations, yet the precise pathological mechanism remains incompletely understood. A variety of pathogeneses has ...been proposed, which suggests that there exists several clinical subtypes.
Conclusions In this review, we categorize CU into four subtypes: (i) CU with poral occlusion; (ii) CU with acquired generalized hypohidrosis; (iii) CU with sweat allergy; and (iv) idiopathic CU, and discuss diagnostic and treatment options.
The nuclear spin–lattice relaxation time (T1) of lanthanum and aluminum nuclei in a single crystal of lanthanum aluminate doped with neodymium ions is studied to estimate the feasibility of the ...dynamically polarized lanthanum target applicable to beam experiments. The application of our interest is the study of fundamental discrete symmetries in the spin optics of epithermal neutrons. This study requires a highly flexible choice of the applied magnetic field for neutron spin control and favors longer T1 under lower magnetic field and at higher temperature. The T1 of 139La and 27Al was measured under magnetic fields of 0.5–2.5 T and at temperatures of 0.1–1.5 K and found widely distributed up to 100 h. The result suggests that the T1 can be as long as T1∼ 1 h at 0.1 K with a magnetic field of 0.1 T, which partially fulfills the requirement of the neutron beam experiment. Possible improvements to achieve a longer T1 are discussed.
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