Low vitamin D associated with high parathyroid hormone (PTH) is commonly reported in the context of HIV infection. We determined the association between total 25-hydroxyvitamin-D [25(OH)D] and PTH in adolescents living with HIV, in Zambia and Zimbabwe. Adolescents (11-19 years) perinatally-infected with HIV and established on antiretroviral therapy (ART) for ≥6 months were recruited into a cross-sectional study. Socio-demographic and clinical characteristics were recorded, anthropometry measured, and fasted serum concentrations of 1,25-dihydroxyvitamin-D (1,25(OH)2D), total 25(OH)D and intact PTH measured. The association between total 25(OH)D and PTH was examined using natural cubic spline regression modelling. 842 participants (female: 53.2%) with median age 15.5 (IQR:13.2-17.9) years were enrolled. Median ART duration was 9.8 [IQR:6.3-12.3] years and 165/841 (19.6%) had an HIV viral load >60copies/ml. Stunting (HAZ score<-2) and underweight (WAZ score<-2) were observed in 29.9% and 30.0% respectively. Three quarters (n=639) reported daily calcium intakes <150mg/day. The mean (SD) concentrations of total 25(OH)D and 1,25(OH)2D were 66.1(16.5) nmol/L and 210.6(70.4) pmol/L respectively, and median PTH level was 4.3 (IQR:3.3-5.5) pmol/L. There was an inverse non-linear relationship between total 25(OH)D and PTH, 25(OH)D levelling-off at 74.6nmol/L (95%CI: 74.5-75.2). Results were consistent in those taking tenofovir disoproxil fumarate (81.7%) and in those who were virally unsuppressed. In this population with extremely low habitual calcium intakes, the lack of association between 25(OH)D and PTH when 25(OH)D exceeded 75nmol/L, potentially suggests levels of 25(OH)D >75nmol/l may need to be achieved to improve bone health; investigation is needed in future research studies.

Gypsy, Roma and Traveller (GRT) communities have considerably worse mental health outcomes than the general population and many other ethnic minority groups. We argue that there is a dynamic, interplaying ‘accessibility mismatch’, resulting in a failure of healthcare services to adequately understand and work with GRT communities in a meaningful way. The consequences are limited engagement and poor health outcomes. Contact with services is often at crisis points, such as in forensic services, which reinforces existing prejudice. Research is limited, and therefore so is the evidence base. It is critical that the UK's National Health Service takes a culturally informed approach to co-produce services that are accessible and responsive to GRT communities. Here we offer practical actions that healthcare organisations can undertake to help redress imbalances and increase equity of healthcare outcomes for these overlooked populations.

OBJECTIVES/GOALS: Determine how a history of unpredictable foot shock in mice affects brain wide patterns of neural activation to future stressors. Additionally, we aimed to characterize how the paraventricular nucleus of the thalamus (PVT) is involved in the fear sensitization process. METHODS/STUDY POPULATION: We used a mouse model of stress enhanced fear learning, where stressed mice are first subjected to a series of unpredictable foot shocks in a novel context while control mice undergo exposure to the novel context without experiencing foot shock. Mice are then left undisturbed for 28 days, following which they are exposed to a single foot shock in a novel context. Mice are tested in the second context 24 hours after single shock, and the amount of time spent frozen in the context provides a measure of fear sensitization. Whole brain patterns of activation during the second context test will be assessed via whole brain optical clearing with antibody staining of immediate early genes. The role of the PVT in fear sensitization will be characterized using chemogenetic approaches. RESULTS/ANTICIPATED RESULTS: Our preliminary results demonstrate that mice display enhanced fear acquisition long after the initial experience of unpredictable shocks. We anticipate to identify regions previously implicated in fear learning and novel regions not previously described through our brain clearing approach. In addition, we anticipate chemogenetic inhibition of the PVT will reduce freezing to an auditory cue associated with the shock in the second context but not to the context itself. DISCUSSION/SIGNIFICANCE: Our findings will provide a comprehensive view of how a history of unpredictable stress affects whole brain processing of subsequent stressful experiences, and describe the role of the PVT in cued fear sensitization.

Marine megafauna occurrence was recorded in the deep-sea region bordering the abyssal plain ~400 km north-west of Luanda, Angola. The survey took place during an Environmental Baseline Study (EBS), prior to drilling exploration activities, with the goal of characterizing the habitat and biodiversity of the region. Offshore shipboard surveys were conducted during September 2018 in water depths ranging from 2350–3850 m. We recorded daytime sightings of marine mammals and sea turtles and at night made audio recordings using passive acoustic monitoring (PAM) methods focused on capturing the sounds of vocalizing marine mammals. A variety of species were visually detected, including the humpback whale (Megaptera novaeangliae), sperm whale (Physeter macrocephalus), common dolphin (Delphinus spp.), striped dolphin (Stenella coeruleoalba), Atlantic spotted dolphin (S. frontalis), and olive ridley turtle (Lepidochelys olivacea). Acoustic click bouts similar to those made by several odontocete species, possibly including beaked whales, were recorded within the 25–48 kHz range. The humpback whale was the most frequently sighted species, accounting for 56% of mammal sightings, indicating a potential far offshore migratory habitat in this region. Most notably, right whales (probable Eubalaena australis) were visually observed. This is the first confirmed record of right whales in Angolan waters since the early 1900s. As development expands in this offshore region, these data can usefully inform future monitoring and mitigation strategies focused on minimizing impacts to wildlife.

Riboflavin (vitamin B2), as the coenzymes flavin mononucleotide (FMN) and flavin dinucleotide (FAD), is essential for oxidation-reduction reactions and energy metabolism. Riboflavin also interacts with vitamin B12, B6 and folate in one-carbon metabolism, and is required for the conversion of dietary vitamin B6 forms to the coenzyme pyridoxal 5’-phosphate (PLP). Biochemical riboflavin status is rarely measured given the lack of convenient and accessible biomarkers. The current gold-standard marker is erythrocyte glutathione reductase activation coefficient (EGRac) that involves laborious sample processing. High prevalence of riboflavin deficiency (EGRac ≥ 1.4) and suboptimal status (EGRac of 1.3–1.39) have been reported in the UK and Ireland; yet the functional significance is unclear. Plasma riboflavin concentration may serve as an alternative indicator; its association with related metabolites has not yet been investigated. Secondary analysis was conducted to determine the change-point of plasma riboflavin with EGRac, to derive a reference interval for plasma riboflavin, and to determine the association of riboflavin status with plasma PLP, using data of 223 older adult women from a cross-sectional study. Fasting blood samples and sociodemographic, anthropometric and dietary data were available for a convenience sample of 223 older adult women. Plasma PLP and related metabolites were quantified using isotope-dilution liquid chromatography-tandem mass spectrometry. The change-point (95% CI) between EGRac and plasma riboflavin occurred at plasma riboflavin concentration of 26.5 (20.5; 32.5) nmol/L (with EGRac of 1.25). The median (IQR) plasma riboflavin concentration was 15.7 (11.2, 23.8); and the upper and lower limits (90%CI) of the central 95% reference interval were 6.70 (6.33, 7.79) and 64.2 (55.0, 74.6) nmol/L, respectively. Plasma PLP (geometric mean (95%CI)) was significantly lower in women with riboflavin deficiency, 54.0 (46.8, 62.2) nmol/L (n = 64), and suboptimal riboflavin status, 56.1 (48.9, 64.3) nmol/L (n = 48), compared to those with riboflavin adequacy, 135 (112, 161) nmol/L (n = 110). Plasma PLP was positively associated with plasma riboflavin concentration after adjustment for total B6 intake, age, ethnicity, BMI, education, household income and C-reactive protein concentration [β (95% CI) = 1.92 (.670, 3.17) nmol/L; p = 0.003]; a significant interaction between plasma riboflavin and total dietary B6 intake was observed (p = 0.024). In conclusion, we are presenting for the first time a reference range for plasma riboflavin concentration and its change-point with EGRac in healthy women. Vitamin B6 status is strongly associated with riboflavin status; more research is needed to elucidate this relationship in a larger sample and ideally intervention study.

Two broad aims drive weed science research: improved management and improved understanding of weed biology and ecology. In recent years, agricultural weed research addressing these two aims has effectively split into separate subdisciplines despite repeated calls for greater integration. Although some excellent work is being done, agricultural weed research has developed a very high level of repetitiveness, a preponderance of purely descriptive studies, and has failed to clearly articulate novel hypotheses linked to established bodies of ecological and evolutionary theory. In contrast, invasive plant research attracts a diverse cadre of nonweed scientists using invasions to explore broader and more integrated biological questions grounded in theory. We propose that although studies focused on weed management remain vitally important, agricultural weed research would benefit from deeper theoretical justification, a broader vision, and increased collaboration across diverse disciplines. To initiate change in this direction, we call for more emphasis on interdisciplinary training for weed scientists, and for focused workshops and working groups to develop specific areas of research and promote interactions among weed scientists and with the wider scientific community.

Since W. E. B. Du Bois documented the physical and social environments of Philadelphia’s predominantly African American Seventh Ward over a century ago, there has been continued interest in understanding the distribution of social and physical environments by racial make-up of communities. Characterization of these environments allows for documentation of inequities, identifies communities which encounter heightened risk, and can inform action to promote health equity. In this paper, we apply and extend Du Bois’s approach to examine the contemporary distribution of physical environmental exposures, health risks, and social vulnerabilities in the Detroit metropolitan area, one of the most racially-segregated areas in the United States. We begin by mapping the proximity of sensitive populations to hazardous land uses, their exposure to air pollutants and associated health risks, and social vulnerabilities, as well as cumulative risk (combined proximity, exposure, and vulnerability), across Census tracts. Next, we assess, quantitatively, the extent to which communities of color experience excess burdens of environmental exposures and associated health risks, economic and age-related vulnerabilities, and cumulative risk. The results, depicted in maps presented in the paper, suggest that Census tracts with greater proportions of people of color disproportionately encounter physical environmental exposures, socioeconomic vulnerabilities, and combined risk. Quantitative tests of inequality confirm these distributions, with statistically greater exposures, vulnerabilities, and cumulative risk in Census tracts with larger proportions of people of color. Together, these findings identify communities that experience disproportionate cumulative risk in the Detroit metropolitan area and quantify the inequitable distribution of risk by Census tract relative to the proportion of people of color. They identify clear opportunities for prioritizing communities for legislative, regulatory, policy, and local actions to promote environmental justice and health equity.

We show how to write the solution to the generalized drift Skorokhod problem in one-dimension in terms of the supremum of the solution of a tractable unrestricted integral equation (that is, an integral equation with no boundaries). As an application of our result, we equate the transient distribution of a reflected Ornstein–Uhlenbeck (OU) process to the first hitting time distribution of an OU process (that is not reflected). Then, we use this relationship to approximate the transient distribution of the GI/GI/1 + GI queue in conventional heavy traffic and the M/M/N/N queue in a many-server heavy traffic regime.

Increasing racial and ethnic group representation in justice-related occupations is considered a potential remedy to racial inequality in justice administration, including sentencing disparity. Studies to date yield little evidence of such an effect; however, research limitations may account for the mixed and limited evidence of the significance of justice workforce racial diversity. Specifically, few studies consider group-level dynamics of race and representation, thus failing to contextualize racial group power relations in justice administration. To consider these contextual dynamics we combine court organizational and case-level data from 89 federal districts and use hierarchical models to assess whether variably “representative” work groups relate to district-level differences in sentencing. Using district-specific indexes of population and work group dissimilarity to define representation, we find no relationships between black judge representation and sentencing in general across districts, but that districts with more black representation among prosecutors are significantly less likely to sentence defendants to terms of imprisonment. We also find in districts with increased black representation among prosecutors, and to a lesser degree among judges, that black defendants are less likely to be imprisoned and white defendants are more likely to be imprisoned, with the effect of narrowing black-white disparities in sentencing. Consistent with the “power-threat” perspective, and perhaps “implicit racial bias” research, findings encourage modeling diversity to account for relative racial group power in processes of social control and suggest that racial justice may be moderately advanced by equal representation among authorities.

In this paper, we consider a single-server queue with stationary input, where each job joining the queue has an associated deadline. The deadline is a time constraint on job sojourn time and may be finite or infinite. If the job does not complete service before its deadline expires, it abandons the queue and the partial service it may have received up to that point is wasted. When the queue operates under a first-come-first served discipline, we establish conditions under which the actual workload process—that is, the work the server eventually processes—is unstable, weakly stable, and strongly stable. An interesting phenomenon observed is that in a nontrivial portion of the parameter space, the queue is weakly stable, but not strongly stable. We also indicate how our results apply to other nonidling service disciplines. We finally extend the results for a single node to acyclic (feed-forward) networks of queues with either per-queue or network-wide deadlines.

Cholestyramine, the first bile acid sequestrant to be marketed, has been in use for over 20 years. Despite its low potency, requiring 16-24 g of polymer to achieve 20% LDL cholesterol reduction in hypercholesterolemic individuals, only one other sequestrant, colestipol, has come to market in the ensuing period. GelTex Pharmaceuticals has been involved for over six years in the discovery and development of new, more potent polymeric sequestrants. Two binding mechanisms are presented — one that operates via an aggregate binding structure and one that is effective via a defined site binding structure. These two binding mechanisms are compared and contrasted through bile acid binding isotherms. The best of these new sequestrants bind bile acids through a combination of hydrophobicity and ion exchange. Optimization and balancing of each of these interactions led us to more potent materials. The first of these, colesevelam hydrochloride is expected to be three to four times more potent than cholestyramine. A third generation product is still in research at GelTex. With another twofold increase in potency possible, single tablet therapy may become a reality.