The fuel form developed for the Transformational Challenge Reactor demonstration program leverages recent advances in manufacturing, materials, and computational sciences, delivering a new ...architecture for production of high-performance microencapsulated nuclear fuels. The fuel consists of conventionally manufactured uranium nitride tristructural isotropic fuel particles embedded inside a 3D-printed silicon carbide matrix. This paper describes the overall architecture and manufacturing process for this fuel form, its properties and behavior, and the ongoing development activities.
•A process for producing a metal phase change material was developed.•For the first time, Al metal has been encapsulated in SiC as a liquid.•SiC does not require expensive structural materials for ...compatibility.
Thermal energy storage (TES) is a broad-based technology for reducing CO2 emissions and advancing concentrating solar, fossil, and nuclear power through improvements in efficiency and economics. Phase change materials (PCMs) are of interest as TES media because of their ability to store large amounts of heat in relatively small volumes. The volume expansion during a phase change, typically between a solid and liquid, can cause breakage of protective coatings. This effort reports on the fabrication of a ceramic encapsulated metal (CEM) high temperature TES technology using a rotary calcining furnace and a fluidized bed chemical vapor deposition coating technique. Aluminum beads were chosen as the PCM because Al has a high melting point (660 °C), low cost, high heat of fusion, and an ability to form a thin, strong alumina layer capable of supporting the Al melt for subsequent processing. Quite remarkably, this study shows that 1 mm diameter Al can be fluidized up to at least 1500 °C in an appropriate atmosphere while maintaining a spheroid geometry. This allowed for producing a first of a kind CEM whereby Al particles were encapsulated in pyro-carbon (PyC) and high purity, dense chemical vapor deposited SiC. The CEM with a PyC only coating was exposed to thermal cycling to test the performance with a differential scanning calorimeter; the melting point and latent heat were measured to be 648.4 ± 2.8 °C and 293.3 ± 6.2 J/g respectively. It was demonstrated that the CEM design is possible to produce, laying the foundation for manufacturing of high temperature, tunable, TES media.
Mortality and the burden of diseases worldwide continue to reach substantial numbers with societal development and urbanization. In the face of decline in human health, early detection of complex ...diseases is indispensable, albeit challenging. In this review, we document the research carried out thus far on the appearance of complex diseases marked by a critical transition or a sudden shift from a healthy state to a disease state. The theory of resilience and critical slowing down can provide practical tools to forecast the onset of various fatal and perpetuating diseases. However, critical transitions in diseases across diverse temporal and spatial scales may not always be preceded by critical slowing down. In this backdrop, an in-depth study of the underlying molecular mechanisms provides dynamic network biomarkers that can forecast potential critical transitions. We have put together the theory of complex diseases and resilience, and have discussed the need for advanced research in developing early warning signals in the field of medicine and health care. We conclude the review with a few open questions and prospects for research in this emerging field.
Purpose
Ensuring and measuring adherence to prescribed exercise regimens are fundamental challenges in intervention studies to promote exercise in adults with cancer. This study reports exercise ...adherence in women who were asked to walk 150 min/week throughout chemotherapy treatment for early breast cancer. Participants were asked to wear a Fitbit
TM
throughout their waking hours, and Fitbit steps were uploaded directly into study computers.
Methods
Descriptive statistics are reported, and both unadjusted and multivariable linear regression models were used to assess associations between participant characteristics, breast cancer diagnosis, treatment, chemotherapy toxicities, and patient-reported symptoms with average Fitbit steps/week.
Results
Of 127 women consented to the study, 100 had analyzable Fitbit data (79%); mean age was 48 and 31% were non-white. Mean walking steps were 3956 per day. Nineteen percent were fully adherent with the target of 6686 steps/day and an additional 24% were moderately adherent. In unadjusted analysis, baseline variables associated with
fewer
Fitbit steps were: non-white race (
p
= 0.012), high school education or less (
p
= 0.0005), higher body mass index (
p
= 0.0024), and never/almost never drinking alcohol (
p
= 0.0048). Physical activity variables associated with
greater
Fitbit steps were: pre-chemotherapy history of vigorous physical activity (
p
= 0.0091) and higher self-reported walking minutes/week (
p
< 0.001), and higher outcome expectations from exercise (
p
= 0.014). Higher baseline anxiety (
p
= 0.03) and higher number of chemotherapy-related symptoms rates “severe/very severe” (
p
= 0.012) were associated with fewer steps. In multivariable analysis, white race was associated with 12,146 greater Fitbit steps per week (
p
= 0.004), as was self-reported walking minutes prior to start of chemotherapy (
p
< 0.0001).
Conclusions
Inexpensive commercial-grade activity trackers, with data uploaded directly into research computers, enable objective monitoring of home-based exercise interventions in adults diagnosed with cancer. Analysis of the association of walking steps with participant characteristics at baseline and toxicities during chemotherapy can identify reasons for low/non-adherence with prescribed exercise regimens.
Purpose
It is not known whether chemotherapy-related symptom experiences differ between Black and White women with early breast cancer (Stage I–III) receiving current chemotherapy regimens and, in ...turn, influences dose delay, dose reduction, early treatment discontinuation, or hospitalization.
Methods
Patients self-reported their race and provided symptom reports for 17 major side effects throughout chemotherapy. Toxicity and adverse events were analyzed separately for anthracycline and non-anthracycline regimens. Fisher’s exact tests and two-sample t-tests compared baseline patient characteristics. Modified Poisson regression estimated relative risks of moderate, severe, or very severe (MSVS) symptom severity, and chemotherapy-related adverse events.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.no changes
Results
In 294 patients accrued between 2014 and 2020, mean age was 58 (SD13) and 23% were Black. For anthracycline-based regimens, the only significant difference in MSVS symptoms was in lymphedema (41% Black vs 20% White,
p
= .04) after controlling for axillary surgery. For non-anthracycline regimens, the only significant difference was MSVS peripheral neuropathy (41% Blacks vs. 23% White) after controlling for taxane type (
p
= .05) and diabetes (
p
= .05). For all other symptoms, severity scores were similar. Dose reduction differed significantly for non-anthracycline regimens (49% Black vs. 25% White,
p
= .01), but not for anthracycline regimens or in dose delay, early treatment discontinuation, or hospitalization for either regimen.
Conclusion
Except for lymphedema and peripheral neuropathy, Black and White patients reported similar symptom severity during adjuvant chemotherapy. Dose reductions in Black patients were more common for non-anthracycline regimens. In this sample, there were minimal differences in patient-reported symptoms and other adverse outcomes in Black versus White patients.
Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought ...to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.
In humans, disruption of nonsense-mediated decay (NMD) has been associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorder and intellectual disability. However, the ...mechanism by which deficient NMD leads to neurodevelopmental dysfunction remains unknown, preventing development of targeted therapies. Here we identified novel protein-coding UPF2 (UP-Frameshift 2) variants in humans with NDD, including speech and language deficits. In parallel, we found that mice lacking Upf2 in the forebrain (Upf2 fb-KO mice) show impaired NMD, memory deficits, abnormal long-term potentiation (LTP), and social and communication deficits. Surprisingly, Upf2 fb-KO mice exhibit elevated expression of immune genes and brain inflammation. More importantly, treatment with two FDA-approved anti-inflammatory drugs reduced brain inflammation, restored LTP and long-term memory, and reversed social and communication deficits. Collectively, our findings indicate that impaired UPF2-dependent NMD leads to neurodevelopmental dysfunction and suggest that anti-inflammatory agents may prove effective for treatment of disorders with impaired NMD.
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•Humans carrying novel variants in UPF2 exhibit speech and language deficits•Upf2-deficient mice and flies have impaired NMD and exhibit behavioral deficits•Inhibition of Upf2-dependent NMD triggers immune activation in mice•Reduction of brain inflammation reverses synaptic and behavioral deficits
Johnson et al. discovered that genetic ablation of Upf2-mediated NMD triggers an aberrant immune response and leads to memory, synaptic plasticity, social, and vocal communication deficits. These behavioral and neurophysiological abnormalities were reversed by FDA-approved agents that dampen brain inflammation.
The objective of this study was to determine if the extent of quantitative troponin elevation predicted mortality as well as in-hospital complications of cardiac arrest, new heart failure and ...cardiogenic shock.
16,318 patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) from the Global Registry of Acute Coronary Events (GRACE) were included. The maximum 24 h troponin value as a multiple of the local laboratory upper limit of normal was used. The population was divided into five groups based on the degree of troponin elevation, and outcomes were compared. An adjusted analysis was performed using quantitative troponin as a continuous variable with adjustment for known prognostic variables.
For each approximate 10-fold increase in the troponin ratio, there was an associated increase in cardiac arrest, sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (1.0, 2.4, 3.4, 5.9 and 13.4%; p<0.001 for linear trend), cardiogenic shock (0.5, 1.4, 2.0, 4.4 and 12.7%; p<0.001), new heart failure (2.5, 5.1, 7.4, 11.6 and 15.8%; p<0.001) and mortality (0.8, 2.2, 3.0, 5.3 and 14.0%; p<0.001). These findings were replicated using the troponin ratio as a continuous variable and adjusting for covariates (cardiac arrest, sustained VT or VF, OR 1.56, 95% CI 1.39 to 1.74; cardiogenic shock, OR 1.87, 95% CI 1.61 to 2.18; and new heart failure, OR 1.57, 95% CI 1.45 to 1.71). The degree of troponin elevation was predictive of early mortality (HR 1.61, 95% CI 1.44 to 1.81; p<0.001 for days 0-14) and longer term mortality (HR 1.18, 95% CI 1.07 to 1.30, p=0.001 for days 15-180).
The extent of troponin elevation is an independent predictor of morbidity and mortality.
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