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Depth-sensing transmission electron microscopic (TEM) in situ mechanical testing has become widely utilized for understanding deformation in irradiated materials. Until now, compression pillars have primarily been used to study the elastic properties and yield of irradiated materials. In this study, we utilize TEM in situ compression pillars to investigate plastic deformation in two ion-irradiated alloys: Fe–9% Cr oxide dispersion strengthened (ODS) alloy and nanocrystalline Cu–24% Ta. We develop an algorithm to automate the extraction of instantaneous pillar dimensions from TEM videos, which we use to calculate true stress–strain curves and strain hardening exponents. True stress–strain curves reveal intermitted plastic flow in all specimen conditions. In the Fe–9% Cr ODS, intermitted plastic flow is linked to strain bursts observed in TEM videos. Low strain hardening or strain softening is observed in all specimen conditions. TEM videos link the strain softening in irradiated Fe–9% Cr ODS to dislocation cross-slip, and in Cu–24% Ta to grain boundary sliding.
Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3–30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.
Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer.
This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52.
The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03).
Significance of results
A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.
In drop-on-demand inkjet printheads, ink is pumped steadily through small channels, each of which contains an actuator and a nozzle. When an actuator pulses, a droplet is forced through the nozzle, after which acoustic oscillations reverberate within the channel. Manufacturers would like to damp the residual reverberations, without increasing the pressure drop required to drive the steady flow. In this paper we use gradient-based optimization to show that this can be achieved by constricting the channel where the acoustic velocity is largest and enlarging the channel where the acoustic velocity is smallest. This increases the viscothermal dissipation of the acoustics without changing the viscous dissipation of the steady flow. We separate the compressible Navier–Stokes equations into equations for a steady flow with no oscillations and equations for oscillations with no steady flow. We define two objective functions: the viscous dissipation of the steady flow and the dissipation of the oscillations. We then derive the adjoints for both sets of equations, and obtain expressions for the gradient of each objective function with respect to boundary deformations in Hadamard form. We combine these with a gradient-based optimization algorithm, incorporating constraints such as the shapes of the actuator and nozzle. This algorithm quickly converges to a design that has the same viscous dissipation for the steady flow but a 50 % larger decay rate for the oscillating flow. We show that this design is nearly optimal. It is a shape that inkjet manufacturers, using physical insight and trial and error, have probably not yet considered. We also show how the adjoint fields provide physical insight into the mechanisms affecting each objective function. The main requirements of this method are that the steady flow Mach number and oscillating flow Mach number are small, and that dissipation is dominated by thermoviscous mechanisms. These requirements are often satisfied in microfluidics, so the method in this paper could be applied to many other applications.
Deep reinforcement learning (deep RL) has achieved superior performance in complex sequential tasks by using deep neural networks as function approximators to learn directly from raw input images. However, learning directly from raw images is data inefficient. The agent must learn feature representation of complex states in addition to learning a policy. As a result, deep RL typically suffers from slow learning speeds and often requires a prohibitively large amount of training time and data to reach reasonable performance, making it inapplicable to real-world settings where data are expensive. In this work, we improve data efficiency in deep RL by addressing one of the two learning goals, feature learning. We leverage supervised learning to pre-train on a small set of non-expert human demonstrations and empirically evaluate our approach using the asynchronous advantage actor-critic algorithms in the Atari domain. Our results show significant improvements in learning speed, even when the provided demonstration is noisy and of low quality.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
This article explores the origins of youth engagement in school, community and democracy. Specifically, it considers the role of psychosocial or non-cognitive abilities, like grit or perseverance. Using a novel original large-scale longitudinal survey of students linked to school administrative records and a variety of modeling techniques – including sibling, twin and individual fixed effects – the study finds that psychosocial abilities are a strong predictor of youth civic engagement. Gritty students miss less class time and are more engaged in their schools, are more politically efficacious, are more likely to intend to vote when they become eligible, and volunteer more. Our work highlights the value of psychosocial attributes in the political socialization of young people.
We study at-the-market (ATM) equity offerings, which are direct share issuances sold in the secondary market that forgo underwriters and “dribble-out” shares over time rather than raising them all at once. Enabled in 2008, their use has increased dramatically, and in 2016, their incidence and total proceeds were, respectively, 63% and 26% of those for seasoned equity offerings (SEOs). Determinants of firms’ choice between ATMs and SEOs are consistent with the costly certification hypothesis of Chemmanur and Fulghieri (1994). We also find that 65% of ATM proceeds are used to stockpile cash compared to 84% of SEO proceeds.
We describe a new stylonurid eurypterid from the evaporitic potassium-salt deposits of the Upper Devonian (Famennian) Soligorsk Formation in the Pripyat Trough of Belarus. All specimens are assigned to Soligorskopterus tchepeliensis new genus new species, which represents the first formally described eurypterid species from Belarus. The occurrence of well-preserved eurypterids in these unusual evaporite deposits is most likely due to transport from freshwater stream habitats into a hypersaline setting following death. Soligorskopterus tchepeliensis n. gen. n. sp. appears to be intermediate between the traditionally considered parastylonurids and stylonurids and thus extends our understanding of stylonurid evolution in the mid-Paleozoic. Soligorskopterus n. gen. extends the occurrence of Famennian eurypterids into eastern Laurussia and the Stylonuridae into the Upper Devonian, and this taxon could be part of a global eurypterid habitat shift that took place in the Late Devonian.
Symbiotic relationships are a common phenomenon among marine invertebrates, forming both obligatory and facultative dependencies with their host. Here, we investigate and compare the population structure of two crustacean species associated with both shallow and mesophotic ecosystems: an obligate symbiont barnacle (Ceratoconcha domingensis), of the coral Agaricia lamarcki and a meiobenthic, free-living harpacticoid copepod (Laophontella armata). Molecular analyses of the Cytochrome Oxidase Subunit I (COI) gene revealed no population structure between mesophotic and shallow barnacle populations within south-west Puerto Rico (ΦST = 0.0079, P = 0.33). The absence of population structure was expected due to the pelagic naupliar larvae of the barnacles and the connectivity patterns exhibited by the coral itself within the same region. Laophontella armata exhibited significant structure based on the mitochondrial COI gene between the mesophotic reef ecosystem of El Seco, Puerto Rico and mangrove sediments of Curaçao (ΦST = 0.2804, P = 0.0). The El Seco and Curaçao copepods shared three COI haplotypes despite the obligatory benthic development of harpacticoid copepods and the geographic distance between the two locations. Three other COI haplotypes from El Seco exhibited higher than expected (up to 7%) intra-species variability, potentially representing three new cryptic species of harpacticoid copepods or rare, deeply divergent lineages of L. armata. This result is evidence for the urgent need of a deeper investigation into the meiofauna diversity associated with mesophotic coral ecosystems (MCEs), arguably the most diverse metazoan component of MCEs.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.
The study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.
The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI.
A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data.
AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001).
Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217–222)
This article creates a new database that covers all U.S. banks in the census years between 1870 and 1900 to test the interaction between inequality and financial development when the banking system was starting over from scratch. A fixed-effects panel regression shows that the number of banks per thousand people in the South has a strong positive relationship with the size of farm operations. This suggests that large southern farm operators welcomed new banks after the Civil War. When the analysis is extended into the 1900s, the relationship becomes more negative, as bankers may have tried to block entrants.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
A non-holonomic robot with a bounded control input travels in a dynamic unknown 3D environment with moving obstacles. We propose a 3D navigation strategy to reach a given final destination point while avoiding collisions with obstacles. A formal analysis of the proposed 3D robot navigation algorithm is given. Computer simulation results and experiments with a real flying autonomous vehicle confirm the applicability and performance of the proposed guidance approach.
OBJECTIVES/SPECIFIC AIMS: Endogenous RT (eRT) is necessary for the function of retrotransposons, elements that replicate via an RNA intermediate. One source of eRT activity is long interspersed elements (LINE). LINEs, of which there are several subgroups (L1, L2, L3), are retrotransposons that regulate cellular growth and gene expression. Given their diverse and important roles, we hypothesized that L1 elements regulate functional responses in megakaryocytes and platelets; a concept not yet examined in the field. METHODS/STUDY POPULATION: To study eRT in human platelets we used RT activity assays, PCR, and Western blot approaches. Furthermore, we used an RT-inhibitor to dissect the function of eRT, analyzed RT-dependent protein synthetic capacity, and immunoprecipitated RNA-DNA hybrids. RNA-DNA hybrids were also detected by means of ICC and automated analysis using CellProfiler software. RNA-DNA hybrids were validated by PCR and eRT regulated synthesis of target proteins was analyzed using autoradiography and Western blot techniques. Platelets from patients with HIV+ were examined in parallel. RESULTS/ANTICIPATED RESULTS: We identified that highly purified, isolated platelets from healthy subjects possess eRT activity. eRT activity was blocked with the non-nucleoside RT inhibitor nevirapine at concentrations within the therapeutic drug range. L1 elements are bicistronic, containing 2 open reading frames (ORFs), ORF1 and ORF2. Thus, we next identified that human platelets express full-length L1 mRNA containing ORF1 and ORF2. In human platelets, eRT activity was localized to L1 protein containing ribonucleo particles. Platelet eRT reverse transcribed exogenous RNAs, a process inhibited by nevirapine, acting in trans using the 3′-UTR of exogenous mRNAs as a template. To dissect the function of eRT in platelets, we next examined cytoskeletal and protein synthetic events in the presence or absence of nevirapine. Inhibition of eRT in isolated platelets led to characteristically beaded platelets in appearance, strongly resembling bone marrow proplatelets. Parallel increases in platelet reactivity were also observed. As these changes occurred over hours, not minutes, we hypothesized that inhibition of eRT would affect platelet protein synthetic events. Consistent with this, RT inhibition resulted in upregulation of global platelet protein synthesis. We validated upregulation of the synthesis of specific proteins (mitofilin, p-selectin, and L26—a component of the 60S ribosomal subunit essential for mRNA translation). RNA-DNA hybrids, noncanonical nucleic acid structures that regulate gene expression, are enriched in regions where L1 is abundant. RNA-DNA hybrids were present in platelets and expression confirmed via differential digestion of RNAs (eg, with RNase A and RNAse I). Next-generation sequencing of pulled down (eg, immunoprecipitated) platelet RNA-DNA hybrids identified numerous differentially expressed transcripts and we focused on MAP1LC3B (LC3B), a primary regulator of autophagy. Hybrid sequencing results for LC3B were validated using qPCR and we confirmed that LC3B RNA binds to L1-encoded RNA binding protein. Platelets treated with nevirapine had increased total LC3B protein expression. As RT inhibition is an important mechanism to control HIV infection, we examined platelet morphology, activation, and LC3B expression in platelets from HIV+ subjects treated with nevirapine. HIV+ patients treated with RT inhibitors had higher numbers of platelets that were beaded in appearance at baseline, increased platelet reactivity, and differential LC3B expression compared with healthy controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Taken together, these results demonstrate that platelets possess eRT activity that regulates platelet morphology, platelet hyperreactivity, and protein synthetic events. We postulate that eRT activity in platelets may be a new post-transcriptional regulatory checkpoint. Moreover, our findings have implications in HIV+ patients treated with RT inhibitors, where off-target effects may contribute to platelet activation and an increased risk of thrombosis.