Follicular occlusion triad: an isotopic response or adverse effect of rituximab?

Follicular occlusion triad is a symptom complex of three conditions with a similar pathophysiology including hidradenitis suppurativa (HS), dissecting cellulitis of the scalp, and acne conglobata. Although the exact pathogenesis of the triad is unknown, it appears to be related to follicular occlusion in areas with apocrine glands. Wolf isotopic response refers to the occurrence of a new dermatosis at the site of another, unrelated, previously healed dermatosis. We present a 26-year-old man with a history of pemphigus foliaceus (PF) who developed large draining nodules with scarring and sinus tracts, compatible with follicular occlusion triad, preferentially at areas previously affected by PF thirteen months after treatment with rituximab. To the authors' knowledge there are no reported cases of follicular occlusion triad or HS manifesting as an isotopic response. However, one member of the triad, HS, has been reported to occur infrequently following the use of biologic agents such as adalimumab, infliximab, tocilizumab, and rituximab for chronic immune-mediated inflammatory diseases (psoriasis, Crohn disease, rheumatoid arthritis, and ankylosing spondylitis)

Small Platforms, High Return: The Need to Enhance Investment in Small Satellites for Focused Science, Career Development, and Improved Equity

In the next decade, there is an opportunity for very high return on investment of relatively small budgets by elevating the priority of smallsat funding in heliophysics. We've learned in the past decade that these missions perform exceptionally well by traditional metrics, e.g., papers/year/\$M (Spence et al. 2022 -- arXiv:2206.02968). It is also well established that there is a "leaky pipeline" resulting in too little diversity in leadership positions (see the National Academies Report at https://www.nationalacademies.org/our-work/increasing-diversity-in-the-leadership-of-competed-space-missions). Prioritizing smallsat funding would significantly increase the number of opportunities for new leaders to learn -- a crucial patch for the pipeline and an essential phase of career development. At present, however, there are far more proposers than the available funding can support, leading to selection ratios that can be as low as 6% -- in the bottom 0.5th percentile of selection ratios across the history of ROSES. Prioritizing SmallSat funding and substantially increasing that selection ratio are the fundamental recommendations being made by this white paper.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 6 pages, 1 figur

Bypassing cellular EGF receptor dependence through epithelial-to-mesenchymal-like transitions

Over 90% of all cancers are carcinomas, malignancies derived from cells of epithelial origin. As carcinomas progress, these tumors may lose epithelial morphology and acquire mesenchymal characteristics which contribute to metastatic potential. An epithelial-to-mesenchymal transition (EMT) similar to the process critical for embryonic development is thought to be an important mechanism for promoting cancer invasion and metastasis. Epithelial-to-mesenchymal transitions have been induced in vitro by transient or unregulated activation of receptor tyrosine kinase signaling pathways, oncogene signaling and disruption of homotypic cell adhesion. These cellular models attempt to mimic the complexity of human carcinomas which respond to autocrine and paracrine signals from both the tumor and its microenvironment. Activation of the epidermal growth factor receptor (EGFR) has been implicated in the neoplastic transformation of solid tumors and overexpression of EGFR has been shown to correlate with poor survival. Notably, epithelial tumor cells have been shown to be significantly more sensitive to EGFR inhibitors than tumor cells which have undergone an EMT-like transition and acquired mesenchymal characteristics, including non-small cell lung (NSCLC), head and neck (HN), bladder, colorectal, pancreas and breast carcinomas. EGFR blockade has also been shown to inhibit cellular migration, suggesting a role for EGFR inhibitors in the control of metastasis. The interaction between EGFR and the multiple signaling nodes which regulate EMT suggest that the combination of an EGFR inhibitor and other molecular targeted agents may offer a novel approach to controlling metastasis

Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star-black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc-3 yr-1 and the neutron star-black hole merger rate to be between 7.8 and 140 Gpc-3 yr-1, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc-3 yr-1 at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)κ with κ=2.9-1.8+1.7 for z≲1. Using both binary neutron star and neutron star-black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2-0.2+0.1 to 2.0-0.3+0.3M⊙. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3-0.5+0.3 and 27.9-1.8+1.9M⊙. While we continue to find that the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M⊙, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χi≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum

GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo During the Second Part of the Third Observing Run

The third Gravitational-wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin $p_\mathrm{astro} > 0.5$. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with $p_\mathrm{astro} > 0.5$ are consistent with gravitational-wave signals from binary black holes or neutron star-black hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron star-black hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with $p_\mathrm{astro} > 0.5$ across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio