Accelerator Production of Tritium project process waste assessment

DOE has made a commitment to compliance with all applicable environmental regulatory requirements. In this respect, it is important to consider and design all tritium supply alternatives so that they can comply with these requirements. The management of waste is an integral part of this activity and it is therefore necessary to estimate the quantities and specific wastes that will be generated by all tritium supply alternatives. A thorough assessment of waste streams includes waste characterization, quantification, and the identification of treatment and disposal options. The waste assessment for APT has been covered in two reports. The first report was a process waste assessment (PWA) that identified and quantified waste streams associated with both target designs and fulfilled the requirements of APT Work Breakdown Structure (WBS) Item 5.5.2.1. This second report is an expanded version of the first that includes all of the data of the first report, plus an assessment of treatment and disposal options for each waste stream identified in the initial report. The latter information was initially planned to be issued as a separate Waste Treatment and Disposal Options Assessment Report (WBS Item 5.5.2.2)

Why does fertilization reduce plant species diversity? Testing three competition-based hypotheses

1 Plant species diversity drops when fertilizer is added or productivity increases. To explain this, the total competition hypothesis predicts that competition above ground and below ground both become more important, leading to more competitive exclusion, whereas the light competition hypothesis predicts that a shift from below-ground to above-ground competition has a similar effect. The density hypothesis predicts that more above-ground competition leads to mortality of small individuals of all species, and thus a random loss of species from plots. 2 Fertilizer was added to old field plots to manipulate both below-ground and above-ground resources, while shadecloth was used to manipulate above-ground resources alone in tests of these hypotheses. 3 Fertilizer decreased both ramet density and species diversity, and the effect remained significant when density was added as a covariate. Density effects explained only a small part of the drop in diversity with fertilizer. 4 Shadecloth and fertilizer reduced light by the same amount, but only fertilizer reduced diversity. Light alone did not control diversity, as the light competition hypothesis would have predicted, but the combination of above-ground and below-ground competition caused competitive exclusion, consistent with the total competition hypothesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75695/1/j.1365-2745.2001.00662.x.pd

Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype

Rationale: The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. Objectives: To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. Methods: A total of 118 participants younger than 19 years old with PCD were evaluated prospectively at six centers in North America using standardized procedures for diagnostic testing, spirometry, chest computed tomography, respiratory cultures, and clinical phenotyping. Measurements and Main Results: Clinical features included neonatal respiratory distress (82%), chronic cough (99%), and chronic nasal congestion (97%). There were no differences in clinical features or respiratory pathogens in subjects with outer dynein arm (ODA) defects (ODA alone; n = 54) and ODA plus inner dynein arm (IDA) defects (ODA 1 IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/ CA/MTD; n = 40). Median FEV 1 was worse in the IDA/CA/MTD group (72% predicted) versus the combined ODA groups (92% predicted; P = 0.003). Median body mass index was lower in the IDA/ CA/MTD group (46th percentile) versus the ODA groups (70th percentile; P = 0.003). For all 118 subjects, median number of lobes with bronchiectasis was three and alveolar consolidation was two. However, the 5- to 11-year-old IDA/CA/MTD group had more lobes of bronchiectasis (median, 5; P = 0.0008) and consolidation (median, 3; P = 0.0001) compared with the ODA groups (median, 3 and 2, respectively). Similar findings were observed when limited to participants with biallelic mutations. Conclusions: Lung disease was heterogeneous across all ultrastructural and genotype groups, but worse in those with IDA/ CA/MTD ultrastructural defects, most of whom had biallelic mutations in CCDC39 or CCDC40

Improving Research Enrollment of Severe Burn Patients

Enrolling severely burn injured patients into prospective research studies poses specific challenges to investigators. The authors describe their experience of recruiting adults with ≥20% TBSA burns or inhalation injury admitted to a single academic burn unit into observational research with minimally invasive specimen collection. The authors outline iterative changes that they made to their recruitment processes in response to perceived weaknesses leading to delays in enrollment. The primary outcome was the change in days to consent for enrolled patients or cessation of recruitment for nonenrolled patients before and after the interventional modifications. The authors assessed change in overall enrollment as a secondary outcome. Study enrollment was approximately 70% in both 4-month study periods before and after the intervention. Following the intervention, time to consent by surrogate decision maker decreased from a median of 26.5 days (interquartile range [IQR] 14-41) to 3 days (IQR 3-6) (P =.004). Time to initial consent by patient changed from a median of 15 days (IQR 2-30) to 3 days (IQR 2-6) (P =.27). Time to decline for nonenrolled patients decreased from a median of 12 days (IQR 6.5-27) to 1.5 days (IQR 1-3.5) (P =.026). Both the findings of the study and a brief literature review suggest that careful design of the recruitment protocol, increased experience of the study team, and broad time windows for both approach and enrollment improve the efficiency of recruiting critically injured burn patients into research

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia

Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. Objectives: Touse a standard protocol formeasuringnNOtoestablishadiseasespecific cutoff value at one site, and then validate at six other sites. Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results: At the lead site, nNO values in PCD (mean6standard deviation, 20.7624.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, therewas overlapwith cystic fibrosis (134.0673.5; 15.6-386.1 nl/min). The disease-specific nNOcutoff valuewas defined at 77 nl/minute (sensitivity, 0.98; specificity, .0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD

Community-based organization perspectives on participating in state-wide community canvassing program aimed to reduce COVID-19 vaccine disparities in California

Background: Inequities in COVID-19 vaccine accessibility and reliable COVID-related information disproportionately affected marginalized racial and ethnic communities in the U.S. The Get Out the Vaccine (GOTVax) program, an innovative statewide government-funded COVID-19 vaccine canvassing program in California, aimed to reduce structural barriers to COVID-19 vaccination in high-risk communities with low vaccination rates. GOTVax consisted of a community-academic-government partnership with 34 local trusted community-based organizations’ (CBOs) to conduct COVID-19 vaccine outreach, education, and vaccine registration. The purpose of this qualitative evaluation study was to explore the barriers and facilitators of using local CBOs to deploy a geographically, racially, and ethnically diverse state-wide COVID-19 vaccine outreach program. Methods: Semi-structured online interviews were conducted with participating GOTVax CBO leaders from November 2021 to January 2022. Transcripts were analyzed using reflexive thematic analysis. Results: Thirty-one of 34 CBOs participated (91% response rate). Identified themes encompassed both facilitators and barriers to program participation. Key facilitators included leveraging trust through recognized entities; promoting empathetic, tailored outreach; and flexibility of milestone-based CBO funding contracts for rapid program implementation. Barriers included navigating community sociopolitical, geographic, and cultural factors; managing canvassers’ safety; desiring metrics for self-evaluation of outreach success; mitigating canvassing technology challenges; and concerns of program infrastructure initially limiting outreach. CBOs problem-solved barriers with academic and government partners. Conclusions: Between May and December 2021, the GOTVax program reached over 2 million California residents and registered over 60,000 residents for COVID-19 vaccination. Public health campaigns may improve benefits from leveraging the expertise of community-trusted CBOs and universities by providing flexible infrastructure and funding, allowing CBOs to seamlessly tailor outreach most applicable to local minoritized communities

A Seat at the Table: Strategic Engagement in Service Activities for Early-Career Faculty From Underrepresented Groups in the Academy

Many academic institutions strive to promote more diverse and inclusive campuses for faculty, staff, and students. As part of this effort, these institutions seek to include individuals from historically underrepresented groups (URGs)-such as women, people from racial/ethnic minority populations, persons with disabilities-on committees and in other service activities. However, given the low number of faculty members from URGs at many institutions, these faculty members tend to receive more requests to provide service to the institution or department (e.g., serving on committees, mentoring) than their counterparts from majority groups. Faculty members from URGs, especially early-career faculty, thus risk becoming overburdened with providing service at the expense of working on other scholarly activities required for promotion and tenure (i.e., conducting research, publishing). Although many scholars and others have written about this "minority tax" and its implications for early-career faculty from underrepresented racial/ethnic minority groups, fewer have published about how this tax extends beyond racial/ethnic minorities to women and persons with disabilities. Further, the literature provides scant practical advice on how to avoid overburdening early-career faculty from URGs. Here, a group of multidisciplinary early- and mid-career faculty members from URGs seek to provide their peers from URGs with practical strategies for both evaluating the appropriateness of service requests and declining those that are not a good fit. The authors also provide institutional leaders with actionable recommendations to prevent early-career faculty from URGs from becoming overburdened with service

High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity

Planet formation studies are often focused on solar-type stars, implicitly considering our Sun as reference point. This approach overlooks, however, that Herbig Ae/Be stars are in some sense much better targets to study planet formation processes empirically, with their disks generally being larger, brighter and simply easier to observe across a large wavelength range. In addition, massive gas giant planets have been found on wide orbits around early type stars, triggering the question if these objects did indeed form there and, if so, by what process. In the following I briefly review what we currently know about the occurrence rate of planets around intermediate mass stars, before discussing recent results from Herbig Ae/Be stars in the context of planet formation. The main emphasis is put on spatially resolved polarized light images of potentially planet forming disks and how these images - in combination with other data - can be used to empirically constrain (parts of) the planet formation process. Of particular interest are two objects, HD100546 and HD169142, where, in addition to intriguing morphological structures in the disks, direct observational evidence for (very) young planets has been reported. I conclude with an outlook, what further progress we can expect in the very near future with the next generation of high-contrast imagers at 8-m class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables and reference

Separate and combined effects of advanced age and obesity on mammary adipose inflammation, immunosuppression and tumor progression in mouse models of triple negative breast cancer

Introduction: Advanced age and obesity are independent risk and progression factors for triple negative breast cancer (TNBC), which presents significant public health concerns for the aging population and its increasing burden of obesity. Due to parallels between advanced age- and obesityrelated biology, particularly adipose inflammation, we hypothesized that advanced age and obesity each accelerate mammary tumor growth through convergent, and likely interactive, mechanisms. Methods: To test this hypothesis, we orthotopically transplanted murine syngeneic TNBC cells into the mammary glands of young normoweight control (7 months), young diet-induced obese (DIO), aged normoweight control (17 months), and aged DIO female C57BL/6J mice. Results: Here we report accelerated tumor growth in aged control and young DIO mice, compared with young controls. Transcriptional analyses revealed, with a few exceptions, overlapping patterns of mammary tumor inflammation and tumor immunosuppression in aged control mice and young DIO mice, relative to young controls. Moreover, aged control and young DIO tumors, compared with young controls, had reduced abundance ofcytotoxic CD8 T cells. Finally, DIO in advanced age exacerbated mammary tumor growth, inflammation and tumor immunosuppression. Discussion: These findings demonstrate commonalities in the mechanisms driving TNBC in aged and obese mice, relative to young normoweight controls. Moreover, we found that advanced age and DIO interact to accelerate mammary tumor progression. Given the US population is getting older and more obese, age- and obesity-related biological differences will need to be considered when developing mechanism-based strategies for preventing or controlling breast cancer

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD. Objectives: To identify disease-causingmutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD. Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis. Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P , 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEV1), compared with 75 age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.16Hz at 258C), but an abnormal, circular beat pattern. Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function