Segmentation of plate coupling, fate of subduction fluids, and modes of arc magmatism in Cascadia, inferred from magnetotelluric resistivity

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 15 (2014): 4230–4253, doi:10.1002/2014GC005509.Five magnetotelluric (MT) profiles have been acquired across the Cascadia subduction system and transformed using 2-D and 3-D nonlinear inversion to yield electrical resistivity cross sections to depths of ∼200 km. Distinct changes in plate coupling, subduction fluid evolution, and modes of arc magmatism along the length of Cascadia are clearly expressed in the resistivity structure. Relatively high resistivities under the coasts of northern and southern Cascadia correlate with elevated degrees of inferred plate locking, and suggest fluid- and sediment-deficient conditions. In contrast, the north-central Oregon coastal structure is quite conductive from the plate interface to shallow depths offshore, correlating with poor plate locking and the possible presence of subducted sediments. Low-resistivity fluidized zones develop at slab depths of 35–40 km starting ∼100 km west of the arc on all profiles, and are interpreted to represent prograde metamorphic fluid release from the subducting slab. The fluids rise to forearc Moho levels, and sometimes shallower, as the arc is approached. The zones begin close to clusters of low-frequency earthquakes, suggesting fluid controls on the transition to steady sliding. Under the northern and southern Cascadia arc segments, low upper mantle resistivities are consistent with flux melting above the slab plus possible deep convective backarc upwelling toward the arc. In central Cascadia, extensional deformation is interpreted to segregate upper mantle melts leading to underplating and low resistivities at Moho to lower crustal levels below the arc and nearby backarc. The low- to high-temperature mantle wedge transition lies slightly trenchward of the arc.Phil Wannamaker and Virginie Maris gratefully acknowledge funding by the U.S. National Science Foundation under grants EAR08–43725 and EAR08–38043 through the Earthscope and Geophysics programs. The 2D inversion capability received development support under U.S. Department of Energy contract DE-PS36-04GO94001. Rob Evans was supported through Earthscope grant EAR08–44041 and Shane McGary through a National Defense Science and Engineering Graduate (NDSEG) fellowship. Fieldwork in Canada was made possible by an NSERC Discovery Grant and a Canadian Foundation for Innovation award to Martyn Unsworth.2015-05-1

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ

UNLABELLED: NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (\u3e89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence

Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and >18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (>21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Prospective, Early Longitudinal Assessment of Lymphedema-Related Quality of Life Among Patients With Locally Advanced Breast Cancer: The Foundation for Building a Patient-Centered Screening Program

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs. METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher\u27s exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models. RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having BCRL, a proportion that increased over time. About 73% reported fear of BCRL, which was stable over time. Further in time from ALND, patients were more likely to report that BCRL screening reduced fear. Patient-reported BCRL was associated with higher soft tissue sensation intensity, biobehavioral, and resource concerns, absenteeism, and work/activity impairment. Objectively measured BCRL had fewer associations with outcomes. Most patients reported performing prevention exercises, but compliance decreased over time; patient-reported BCRL was not associated with exercise frequency. Fear of BCRL was positively associated with performing prevention exercises and using compressive garments. CONCLUSIONS: Both incidence and fear of BCRL were high after ALND for breast cancer. Fear was associated with improved therapeutic compliance, but compliance decreased over time. Patient-reported BCRL was more strongly associated with worse HRQOL and productivity than was objective BCRL. Screening programs must support patients\u27 psychological needs and aim to sustain long-term compliance with recommended interventions

Post-zygotic rescue of meiotic errors causes brain mosaicism and focal epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development

Post-Zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development

Acquisition of a Unique Onshore/Offshore Geophysical and Geochemical Dataset in the Northern Malawi (Nyasa) Rift

The Study of Extension and maGmatism in Malawi aNd Tanzania (SEGMeNT) project acquired a comprehensive suite of geophysical and geochemical datasets across the northern Malawi (Nyasa) rift in the East Africa rift system. Onshore/offshore active and passive seismic data, long‐period and wideband magnetotelluric data, continuous Global Positioning System data, and geochemical samples were acquired between 2012 and 2016. This combination of data is intended to elucidate the sedimentary, crustal, and upper‐mantle architecture of the rift, patterns of active deformation, and the origin and age of rift‐related magmatism. A unique component of our program was the acquisition of seismic data in Lake Malawi, including seismic reflection, onshore/offshore wide‐angle seismic reflection/refraction, and broadband seismic data from lake‐bottom seismometers, a towed streamer, and a large towed air‐gun source

Post-zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development