Investigations of ash layer characteristics and ash distribution in a diesel particulate filter using novel lubricant additive tracers

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 59, 62).Diesel particulate filters (DPF) are currently widely used in various applications as a means of collecting particulate matter in order to meet increasingly stringent particle emissions regulations. Over time, the DPF slowly accumulates incombustible material or ash, mostly from the metallic additives present in the engine lubricant. This build up of accumulated ash leads to an increase in flow restriction and therefore an increase in pressure drop along the DPF. The increased pressure drop negatively impacts engine performance and fuel economy, and it also requires eventual filter removal for ash cleaning. While the major effects of ash accumulation on DPF performance are known, the fundamental underlying mechanisms are not. This work is focused on understanding key mechanisms, such as the soot deposition and the ash formation, accumulation, and distribution processes, which play a major role in determining the magnitude of the ash effect on DPF pressure drop. More specifically, it explores the location of ash deposit accumulation inside the DPF channels, whether in a layer along the filter walls or packed in a plug at the rear of the channels, which is one of the key factors controlling DPF pressure drop. A specialized experiment was set up by running three different lubricants, each with its own unique additive tracer, sequentially through a diesel burner system. Scanning electron microscopy (SEM) was used to analyze the evolution of the ash deposits in the DPF samples in order to explain the specific mechanisms and processes controlling ash properties and their effect on DPF pressure drop. The experimental results were compared and correlated with previous DPF test data and theoretical models, providing additional insight to optimize diesel particulate filter performance. The results are useful in optimizing the design of the engine, aftertreatment, and lubricant systems for future diesel engines, balancing the requirements of additives for adequate engine protection with the requirements for robust after treatment systems.by Ryan Morrow.S.B

Post-COVID-19 illness trajectory: a multisystem investigation [Pre-print]

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis. Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (p<0.001), illness perception (p<0.001), anxiety and depression (p<0.001), physical activity (p<0.001) and predicted maximal oxygen utilization (ml/kg/min) (p<0.001). These measures were associated with adjudicated myocarditis. Conclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2)

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.</p

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd

Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy1,2,3. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations2. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes1,3. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1)1,3,4. Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.This work was supported by an Alex's Lemonade Stand Young Investigator Award (S.C.M.), The CIHR Banting Fellowship (S.C.M.), The Cancer Prevention Research Institute of Texas (S.C.M., RR170023), Sibylle Assmus Award for Neurooncology (K.W.P.), the DKFZ-MOST (Ministry of Science, Technology & Space, Israel) program in cancer research (H.W.), James S. McDonnell Foundation (J.N.R.) and NIH grants: CA154130 (J.N.R.), R01 CA169117 (J.N.R.), R01 CA171652 (J.N.R.), R01 NS087913 (J.N.R.) and R01 NS089272 (J.N.R.). R.C.G. is supported by NIH grants T32GM00725 and F30CA217065. M.D.T. is supported by The Garron Family Chair in Childhood Cancer Research, and grants from the Pediatric Brain Tumour Foundation, Grand Challenge Award from CureSearch for Children’s Cancer, the National Institutes of Health (R01CA148699, R01CA159859), The Terry Fox Research Institute and Brainchild. M.D.T. is also supported by a Stand Up To Cancer St. Baldrick’s Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113)

Young people’s perspectives of e-cigarette use in the home

There is concern that the emergence of e-cigarettes could result in an increase in young people's intake of, and exposure to, nicotine. This UK study used friendship group interviews to elicit the perspectives of young people from socioeconomically contrasting backgrounds regarding e-cigarettes. Young people from both advantaged and disadvantaged backgrounds described similar e-cigarette practices in the home environment, and, for both health and sensory reasons, viewed these as preferable to tobacco smoking. Space-related practices of adult e-cigarette use in the home were revealed to be more malleable than those of tobacco use. Results also highlighted that e-cigarettes offered young people new opportunities for nicotine consumption in the home. Methods of storing e-cigarettes in domestic spaces posed safety risks to younger children and easy access to e-cigarettes for others

Fusion transmutation of waste: design and analysis of the in-zinerator concept.

Due to increasing concerns over the buildup of long-lived transuranic isotopes in spent nuclear fuel waste, attention has been given in recent years to technologies that can burn up these species. The separation and transmutation of transuranics is part of a solution to decreasing the volume and heat load of nuclear waste significantly to increase the repository capacity. A fusion neutron source can be used for transmutation as an alternative to fast reactor systems. Sandia National Laboratories is investigating the use of a Z-Pinch fusion driver for this application. This report summarizes the initial design and engineering issues of this ''In-Zinerator'' concept. Relatively modest fusion requirements on the order of 20 MW can be used to drive a sub-critical, actinide-bearing, fluid blanket. The fluid fuel eliminates the need for expensive fuel fabrication and allows for continuous refueling and removal of fission products. This reactor has the capability of burning up 1,280 kg of actinides per year while at the same time producing 3,000 MWth. The report discusses the baseline design, engineering issues, modeling results, safety issues, and fuel cycle impact

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)