Recent publications
Rare earth barium copper oxide (REBCO) coated conductor tapes and cables are promising material candidates for constructing high field magnets. In both the magnet constructing stage and operation stage, transverse pressure is exerted on the tapes/cables. Therefore, understanding the mechanical behavior of tapes/cable under transverse pressure and figuring out certain properties, such as modulus and stress limits, will be helpful for magnet design and magnet simulation study. We accomplished these goals by performing compression tests on several commonly used tapes/cables in high field magnets. We found that the mechanical behavior of tape stacks can be characterized in three distinct regimes. In the first regime (<20 MPa), tape stacks underwent flattening and self-relocation. Then in the second regime (20 - 60 MPa), the REBCO tape stack showed a modulus of 3.1
$ \pm $
7% GPa, and the Ni-plated REBCO tape stack showed a modulus of 1.7
$ \pm $
6% GPa. In the third regime (>60 MPa), the REBCO tape stack and its Ni-plated derivative had a modulus of 10
$ \pm $
11% GPa and 4.6
$ \pm $
9% GPa respectively. Roebel cable had similar mechanical behavior to the tape stack with three regimes, and the second and third regimes showed a modulus of 3.1
$ \pm $
5% GPa and 9.1
$ \pm $
11% GPa respectively. The conductor on round core (CORC) cable was more vulnerable to stress, and its fracture stress was around 27 MPa.
Multifilamentary MgB
<sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub>
strands (filament numbers 36 to 114) prepared by the in-situ power-in-tube (PIT) route with carbon doping contents of 0, 2, and 3.2% were wound on barrels for transport
J<sub>c</sub>
and
n
-value measurement at 4.2 K in fields of up to 12 T. The strand and gauge lengths were 1 m and 0.5 m. Heat treatments at 675°C and 650°C centered around the melting point of Mg (650°C) and both utilized the liquid-solid reaction. A pair of strands, with and without 2% C doping exhibited the
J<sub>c</sub>
(B) crossover effect. Studied were the dependencies of
J<sub>c</sub>
on field strength, dopant concentration, and cabling and the dependence of
n
-value on field strength.
The toll like receptors (TLRs) and RIG-1 are proteins involved in the initial reaction of the innate immune system to infectious diseases and, thus, can provide much information to the surgical pathologist in terms of the molecular dynamics of the infection. The TLRs (TLR1, 2, 3, 4, 7, 8) and RIG-1 distribution as determined by immunohistochemistry was examined in the following diseases: human papillomavirus (n = 30 including 15 squamous intraepithelial lesions (SIL), 5 cancers, and 10 controls); molluscum contagiosum (n = 8 including 4 controls), SARS-CoV2 (n = 52 including 20 mild, 5 fatal, and 27 controls) and reovirus infection as oncolytic therapy. Mild, regressing infection (molluscum contagiosum, mild SARS-CoV2 and low grade SIL) each showed the same pattern: marked up regulation of at least three of the TLRs/RIG-1 with decreased expression of none compared to the controls. Severe infection (fatal SARS-CoV2, and cervical cancer) each showed marked decrease expression in at least three of the TLRs/RIG-1. We recently documented an equivalent marked decrease expression of the TLRs/RIG-1 in the placenta in fatal in utero infections. The reoviral infected tissues showed an overall pattern of marked increase expression of TLRs/RIG-1, consistent with a strong anti-viral response. Thus, the in situ testing of infectious diseases by a panel of these early infectious disease recognition proteins may allow the surgical pathologist to predict the outcome of the disease which, in turn, may assist in the understanding of the role of the TLRs/RIG-1 in determining the fate of a given infectious process.
The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.
Electron energy loss spectroscopy (EELS) is a proven tool for probing materials chemistry at high spatial resolution. Core-loss EELS fine structure should allow measurement of local polymer chemistry. For organic materials, sensitivity to radiolysis is expected to limit the resolution achievable with EELS: but core-loss EELS has proven difficult at any resolution, yielding inconsistent spectra that compare unfavorably with theoretically analogous x-ray absorption spectra. Many of the previously identified shortcomings should not be limiting factors on modern equipment. This study establishes that EELS can generate identifiable carbon K-edge spectra for a range of common polymer types and chemistry, and demonstrates fine structure features matching prior x-ray absorption spectra. EELS fine structure features broaden intuitively with the instrument's energy resolution, and beam-induced features are readily differentiated by collecting spectra at a series of doses. The results are demonstrated with spectrum images of a model polymer blend, and used to estimate practical pixel sizes that can be used for mapping core-loss EELS as a function of electron dose.
Background:
Intermittent Explosive Disorder (IED) is a disorder primarily of aggression, defined by recurrent behavioral outbursts out of proportion to provocations or stressors. IED first appears in childhood and adolescence. This study examines the underlying childhood environment of those with IED, particularly familial and school-related factors.
Methods:
Adult participants from a larger study completed diagnostic assessments and a battery of self-report measures. Group assignment was based on the assessment: 1) IED diagnosis; 2) non-IED psychiatric diagnosis; and 3) no significant psychiatric history. Groups were compared on factors of parental demographics, intrafamilial aggression, lifetime syndromal and personality diagnoses, neurodevelopmental and learning difficulties, childhood peer relationships, and juvenile legal issues.
Results:
Significant patterns emerged specific to IED for not being raised by both parents, greater physical aggression to participant, and greater degree of fighting with peers by age ten.
Limitations:
The retrospective, and cross-sectional, nature of the study, which prevent the making of causal inferences, and the basic nature of the questions asked of participants which limit a more nuanced interpretation of the data. A further limitation is bias associated with self-reported responses.
Conclusions:
Results suggest the prevalence childhood adversaries may be linked with IED; the childhood environment of those with IED likely is substantially more tumultuous than individuals with or without other psychiatric disorders.
Every Door Direct Mail (EDDM) is a service of the United States Postal Service (USPS) that delivers non-addressed mail to all postal customers on designated mailing routes. Primarily used for marketing, we describe EDDM's efficacy as a research tool for remotely recruiting a representative convenience sample of rural Appalachian households for a longitudinal survey-based health study. In June 2020, recruitment postcards were sent via EDDM to all residential addresses (n = 31,201) within an 18 ZIP code region of Southeastern Ohio. Adults were invited to complete a survey online via QR code or to call for a mailed survey. Respondent demographic characteristics were generated using SPSS and compared with the region's 2019 U.S. Census Bureau statistics. A total of 841 households responded to the invitation, reflecting a response rate higher than marketing estimates (2.7 % vs 2 %). Compared to Census data, a greater proportion of respondents were female (74 % vs 51 %), and highly educated (64 % vs 36 % college graduates); a comparable proportion were non-Hispanic (99 % vs 98 %), white (90 % vs 91 %), and had ≥ 1 adult in the household (1.7 ± 0.9); and a lower proportion had a household income < $50 k (47 % vs 54 %). The median age was higher (56 vs 30 years), and 29 % were retirees. EDDM was a viable method for remote recruitment of a rural geographically-based sample. Further work is needed to explore its efficacy in recruiting representative samples in other contexts and to inform best practices for its use.
Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.
Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to potential, unpredictable threat and engages the bed nucleus of the stria terminalis (BNST). The BNST has been implicated in PTSD, but the role of the BNST in combat veterans with PTSD has yet to be examined. Identifying alterations in BNST responses to unpredictable threat could provide important new targets for treatment. The current study examined whether veterans with PTSD have altered BNST or amygdala responses (function and connectivity) to unpredictable and predictable threat. The fMRI task involved viewing predictable threat cues followed by threat images, predictable neutral cues followed by neutral images, and unpredictable threat cues followed by either a threat or neutral image. Participants included 32 combat-exposed veterans with PTSD and 13 combat-exposed controls without PTSD. Across all conditions, veterans with PTSD had heightened BNST activation and displayed stronger BNST and amygdala connectivity with multiple fear and anxiety regions (hypothalamus, hippocampus, insula, ventromedial prefrontal cortex) relative to controls. In contrast, combat controls showed a pattern of stronger connectivity during neutral conditions (e.g., BNST-vmPFC), which may suggest a neural signature of resilience to developing PTSD, ηp 2 = .087-.527, ps < .001. These findings have implications for understanding fear and anxiety networks that may contribute to the development and maintenance of PTSD.
Background:
Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive.
Methods:
The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive and not enrolled on the same day as the proband.
Results:
Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90).
Conclusions:
Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of patients with DCM.
Registration:
URL: https://clinicaltrials.gov; Unique identifier: NCT03037632.
The major determinant of disease severity in Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether the dystrophin gene (DMD) mutation truncates the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as modifiers. Here we present the largest genome-wide search to date for loci influencing severity in N = 419 DMD patients. Availability of subjects for such studies is quite limited, leading to modest sample sizes, which present a challenge for GWAS design. We have therefore taken special steps to minimize heterogeneity within our dataset at the DMD locus itself, taking a novel approach to mutation classification to effectively exclude the possibility of residual dystrophin expression, and utilized statistical methods that are well adapted to smaller sample sizes, including the use of a novel linear regression-like residual for time to ambulatory loss and the application of evidential statistics for the GWAS approach. Finally, we applied an unbiased in silico pipeline, utilizing functional genomic datasets to explore the potential impact of the best supported SNPs. In all, we obtained eight SNPs (out of 1,385,356 total) with posterior probability of trait-marker association (PPLD) ≥ 0.4, representing six distinct loci. Our analysis prioritized likely non-coding SNP regulatory effects on six genes (ETAA1, PARD6G, GALNTL6, MAN1A1, ADAMTS19, and NCALD), each with plausibility as a DMD modifier. These results support both recurrent and potentially new pathways for intervention in the dystrophinopathies.
OBJECTIVE
To investigate the effects of interleukin-1β (IL-1β) and methylprednisolone acetate (MPA) on equine intrabursal deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) cells in vitro.
SAMPLE
Third passage DDFT and NBF cells from 5 healthy donor horses ages 11–17 years euthanized for reasons unrelated to musculoskeletal conditions.
PROCEDURES
Aggregate cultures were incubated with culture medium alone (control), 10 ng/mL IL-1β, 10 ng/mL IL-1β + 0.05 mg/mL MPA, or 10 ng/mL IL-1β + 0.5 mg/mL MPA for 24 hours. Extracellular matrix (ECM) gene expressions were assessed via real-time polymerase chain reaction (rtPCR). Culture media matrix metalloproteinase (MMP) -3 and -13 concentrations were quantified via ELISA. Total glycosaminoglycan (GAG) content in the cell pellets and culture media was also assessed.
RESULTS
IL-1β and IL-1β combined with MPA significantly downregulated ECM gene expression to a greater extent in NBF cells compared with DDFT cells. IL-1β and IL-1β combined with MPA significantly upregulated MMP-3 culture media concentrations in DDFT cells only, and MMP-13 culture media concentrations to a greater extent in NBF cells compared with DDFT cells.
CLINICAL RELEVANCE
NBF cells were more susceptible to IL-1β and MPA-mediated ECM gene expression downregulation in vitro. These results serve as a first step for future work to determine intrabursal corticosteroid regimens that limits or resolve the inflammation as well as take into consideration NBF cell biosynthesis in horses with navicular disease, for which currently no information exists.
Mountains are renowned for their bountiful biodiversity. Explanations on the origin of such abundant life are usually regarded to their orogenic history. However, ancient mountain systems with geological stability also exhibit astounding levels of number of species and endemism, as illustrated by the Brazilian Quartzitic Mountains (BQM) in Eastern South America. Thus, cycles of climatic changes over the last couple million years are usually assumed to play an important role in the origin of mountainous biota. These climatic oscillations potentially isolated and reconnected adjacent populations, a phenomenon known as flickering connectivity, accelerating speciation events due to range fragmentation, dispersion, secondary contact, and hybridization. To evaluate the role of the climatic fluctuations on the diversification of the BQM biota, we estimated the ancient demography of distinct endemic species of animals and plants using hierarchical approximate Bayesian computation analysis and Ecological Niche Modeling. Additionally, we evaluated if climatic oscillations have driven a genetic spatial congruence in the genetic structure of co-distributed species from the Espinhaço Range, one of the main BQM areas. Our results show that the majority of plant lineages underwent a synchronous expansion over the Last Glacial Maximum (LGM, ca. 21 thousand years ago), although we could not obtain a clear demographic pattern for the animal lineages. We also obtained a signal of a congruent phylogeographic break between lineages endemic to the Espinhaço Range, suggesting how ancient climatic oscillations might have driven the evolutionary history of the Espinhaço's biota.
Generalized Gauss–Radau (GGR) projections are global projection operators that are widely used for the error analysis of discontinuous Galerkin (DG) methods with generalized numerical fluxes. In previous work, GGR projections were constructed for Cartesian meshes and analyzed through an algebraic approach. In this paper, we first present an alternative energy approach for analyzing the one-dimensional GGR projection, which does not require assembling and explicitly solving a global system over the entire computational domain as that in the algebraic approach. We then generalize this energy argument to construct a global projection operator on special simplex meshes in multidimensions satisfying the so-called flow condition. With this projection, optimal error estimates are proved for upwind-biased DG methods for the linear advection equation on these meshes, which generalizes the error analysis for the purely upwind case by Cockburn et al. (SIAM J Numer Anal 46(3):1250–1265, 2008) in a time-dependent setting.
Previous studies indicate that obesity is a risk factor of suicide behaviors among adolescents. Whether this association has remained consistent during the ongoing obesity epidemic remains unknown. The time trends of the obesity–suicide association were examined using the 1999–2019 biannual Youth Risk Behavior Survey data (n = 161,606). Prevalence odds ratio of suicide behaviors among adolescents with obesity (vs. adolescents with no obesity) for each survey year and time trends using National Cancer Institute Joinpoint regression analysis was calculated. For each year post-baseline, there was a significant increase of prevalence odds ratio of 1.4 (1.2–1.6)–1.6 (1.3–2.0) for suicide ideation, 1.3 (1.1–1.7) –1.7 (1.4–2.0) for plan, and 1.3 (1.0–1.7) –1.9 (1.5–2.4) for an attempt, except for the 2013 survey for attempt (1.19 [0.9–1.6]). Significant positive trends were found from1999 to 2019 for ideation and plan, with biannual %-changes of + 0.92 and + 1.22%, respectively. Adolescents with obesity have consistently higher odds of engaging in suicide behaviors than their peers without obesity since the beginning of the United States obesity epidemic, and this association grew stronger as the obesity epidemic continued.
Deep sequencing of human tumours has uncovered a previously unappreciated role for epigenetic regulators in tumorigenesis. H3K4 methyltransferase KMT2C/MLL3 is mutated in several solid malignancies, including more than 10% of breast tumours. To study the tumour suppressor role of KMT2C in breast cancer, we generated mouse models of Erbb2/Neu, Myc or PIK3CA-driven tumorigenesis, in which the Kmt2c locus is knocked out specifically in the luminal lineage of mouse mammary glands using the Cre recombinase. Kmt2c knock out mice develop tumours earlier, irrespective of the oncogene, assigning a bona fide tumour suppressor role for KMT2C in mammary tumorigenesis. Loss of Kmt2c induces extensive epigenetic and transcriptional changes, which lead to increased ERK1/2 activity, extracellular matrix re-organization, epithelial-to-mesenchymal transition and mitochondrial dysfunction, the latter associated with increased reactive oxygen species production. Loss of Kmt2c renders the Erbb2/Neu-driven tumours more responsive to lapatinib. Publicly available clinical datasets revealed an association of low Kmt2c gene expression and better long-term outcome. Collectively, our findings solidify the role of KMT2C as a tumour suppressor in breast cancer and identify dependencies that could be therapeutically amenable.
Self-regulation can facilitate modifications in lifestyle to promote behavioral change. However, little is known about whether adaptive interventions promote improvement in self-regulatory, dietary, and physical activity outcomes among slow treatment responders. A stratified design with an adaptive intervention for slow responders was implemented and evaluated. Adults ≥ 21 years old with prediabetes were stratified to the standard Group Lifestyle Balance intervention (GLB; n = 79) or the adaptive GLB Plus intervention (GLB + ; n = 105) based on first-month treatment response. Intake of total fat was the only study measure that significantly differed between groups at baseline (P = 0.0071). GLB reported greater improvement in self-efficacy for lifestyle behaviors, goal satisfaction with weight loss, and very active minutes of activity than GLB + (all P < 0.01) at 4-months. Both groups reported significant improvement in self-regulatory outcomes and reduction in energy and fat intake (all P < 0.01). An adaptive intervention can improve self-regulation and dietary intake when tailored to early slow treatment responders.
Objectives:
A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the US population, increasing longevity, and growing racial and ethnic diversity.
Methods:
Participants were women aged ≥80 enrolled in the Women's Health Initiative (WHI). Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES.
Results:
Participants (n=29,367, median age=84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p=0.06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94±0.83, out of 5) and high NSES (4.00±0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES.
Discussion:
Multiple factors were associated with resilience among women aged ≥80 in the WHI. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.
This feature article introduces the use of photo elicita-
tion as a reflection technique for TESOL teacher edu-
cation to explore the connection between emotions
and language teacher identity (LTI). In current TESOL
teacher education, there is limited knowledge about
how to integrate the discussion of emotions and LTI into
language teacher education courses and how to engage
students in this discussion intentionally and effectively.
To address this gap, the authors advocate for the use of
an alternative approach— photo-elicitation—to further
enrich the reflection techniques that can be used to
encourage teacher candidates to discuss and construct
LTI through their emotional experiences. The article
includes a series of tasks that can be used in TESOL
teacher education courses to engage teacher candidates
in reflecting upon their emotional experiences and mak-
ing the connection to their LTI construction.
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