Abstract

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.

The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.

Food pantries provide free food to individuals at nutritional risk given lack of available foods. Frequent use of food pantries is associated with higher dietary quality; however, neither the nutrient contributions of food pantries to participant diets nor their relationship with household food security are known. This cross-sectional analysis used secondary data from rural food pantry participants, including sociodemographic characteristics, household food security and 24-h recalls. Mean intakes of selected food groups and nutrients from food pantries, supermarkets, other stores and restaurants, and other were compared by one-way ANCOVA. Interaction effects of household food security with food sources were evaluated by two-way ANCOVA. About 40 % of participants’ dietary intake came from food pantries. Mean intakes of fibre (P < 0·0001), Na (P < 0·0001), fruit (P < 0·0001), grains (P < 0·0001) and oils (P < 0·0001) were higher from food pantries compared with all other sources, as were Ca (P = 0·004), vitamin D (P < 0·0001) and K (P < 0·0001) from food pantries compared with two other sources. Percentage total energy intake (%TEI) from added sugars (P < 0·0001) and saturated fat (P < 0·0001) was higher from supermarkets than most other sources. Significant interaction effects were observed between food sources and household food security for vegetables (P = 0·01), Na (P = 0·01) and %TEI from saturated fat (P = 0·004), with food-insecure participants having significantly higher intakes from food pantries and/or supermarkets compared with all other sources. Future interventions may incorporate these findings by providing education on purchasing and preparing healthy meals on limited budgets, to complement foods received from pantries, and by reducing Na in pantry environments.

OBJECTIVES/GOALS: The goal of this project was to assess the scientific impact of Miami CTSI’s Mentored Career Development (KL2) Program using bibliometric tools and network visualization in addition to the traditional metrics used to provide a comprehensive evaluation. METHODS/STUDY POPULATION: Scholarly productivity of KL2 scholars were tracked using REDCap. For bibliometric data analysis and visualization, publications were queried using iCite (NIH Office of Portfolio Analysis) and Web of Science database. A total of 173 publications produced by eight KL2 scholars from 2013-2018 were analyzed and categorized into pre-award, during award, and post-award periods. iCite was used to assess scientific influence and translation. Scientific networks and collaboration were visualized using VOSviewer (Centre for Science and Technology Studies, Leiden University). CTSA Common Metrics were tracked using the Results Based Accountability framework. RESULTS/ANTICIPATED RESULTS: Albeit of modest size, the Miami CTSI’s KL2 Program had significant scientific productivity and impact in its first five years. Our KL2 scholars’ publications were cited twice as frequently as other papers in their fields. Further, 48% of publications post KL2 award were above the NIH 50th percentile and had higher citation impact compared to the average NIH-funded paper; 11% were in the top 10% NIH citation ranking. In contrast, only 20% of the publications pre-KL2 award were above the NIH 50th percentile. The program also promoted research collaboration; network visualizations indicate larger co-authorship and organization networks of KL2 scholars post-award. DISCUSSION/SIGNIFICANCE OF IMPACT: Bibliometric and data visualization approaches helped us better identify trends and gauge effectiveness of the KL2 program. These findings provided useful insight into the scientific influence and impact of our scholars’ work.

Many factors such as environment, herbicide rate, growth stage at application, and days between sequential applications can influence the response of a crop to herbicides. Florpyrauxifen-benzyl is a new broad-spectrum, POST herbicide that was commercialized for use in U.S. rice production in 2018. Field experiments were conducted in 2018 at the Pine Tree Research Station (PTRS) near Colt, AR, and the Rice Research and Extension Center (RREC), near Stuttgart, AR, to evaluate crop injury and yield response of three rice cultivars to sequential applications of florpyrauxifen-benzyl. Greenhouse and growth chamber experiments were conducted at the Altheimer Laboratory in Fayetteville, AR, to evaluate cultivar responses when florpyrauxifen-benzyl was applied at 30 or 60 g ae ha−1 to rice exposed to different temperature regimes or at various growth stages. Three rice cultivars were used in all experiments: long-grain variety ‘CL111’, medium-grain variety ‘CL272’, and long-grain hybrid cultivar ‘CLXL745’. CL111 exhibited sufficient tolerance to florpyrauxifen-benzyl with only 10% visible injury and no effect on yield. CL272 showed 15% injury 3 wk after the second application in the field experiment when applications were made 14 d apart. Additionally, 12% injury was observed in greenhouse studies when florpyrauxifen-benzyl was applied at 30 g ae ha−1, averaged over various growth stages at application. Florpyrauxifen-benzyl did not reduce the yield of CL272 in field experiments, indicating that CL272 can recover from florpyrauxifen-benzyl injury. As much as 64% injury was observed for CLXL745 at 3 wk after application (WAA) when sequential herbicide applications were made 4 d apart. High levels of injury occurred in the growth chamber and greenhouse studies for this cultivar as well. Sequential applications of florpyrauxifen-benzyl reduced yields of CLXL745 in nearly all treatments. Data from these experiments suggest that CL272 and CLXL745 are sensitive to sequential applications of florpyrauxifen-benzyl. Growers must follow the prescribed guidelines for using florpyrauxifen-benzyl in these cultivars and others like it.

Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.

A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.

Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.

Medicine-related research includes numerous studies on the hazards of mortality and what risk factors are associated with these hazards, such as diseases and treatments. These hazards are estimated in a sample of people and summarised over the observed period. From these observations, inferences can be made about the underlying population and consequently inform medical guidelines for intervention. New health interventions are usually based on these estimated hazards obtained from clinical trials. A lengthy lead time would be needed to observe their effect on population longevity. This paper shows how estimated mortality hazards can be translated to hypothetical changes in life expectancies at the individual and population levels. For an individual, the relative hazards are translated into the number of years gained or lost in “effective age”, which is the average chronological age with the same risk profile. This translation from hazard ratio to effective age could be used to explain to individuals the consequences of various diseases and lifestyle choices and as a result persuade clients in life and health insurance to pursue a healthier lifestyle. At the population level, a period life expectancy is a weighted average of component life expectancies associated with the particular risk profiles, with the weights defined by the prevalences of the risk factor of interest and the uptake of the relevant intervention. Splitting the overall life expectancy into these components allows us to estimate hypothetical changes in life expectancy at the population level at different morbidity and uptake scenarios. These calculations are illustrated by two examples of medical interventions and their impact on life expectancy, which are beta blockers in heart attack survivors and blood pressure treatment in hypertensive patients. The second example also illustrates the dangers of applying the results from clinical trials to much wider populations.

BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.

A great deal of energy in recent months has been expended in worrying about energy. The procurement, allocation, utilization, and conservation of energy sources have been probed countless times and viewed from almost every possible vantage point. The word “energy” now shares the stage with the word “environment.”

Invasive pneumococcal disease (IPD), caused by infection with Streptococcus pneumoniae, has a substantial global burden. There are over 90 known serotypes of S. pneumoniae with a considerable body of evidence supporting serotype-specific mortality rates immediately following IPD. This is the first study to consider the association between serotype and longer-term mortality following IPD. Using enhanced surveillance data from the North East of England we assessed both the short-term (30-day) and longer-term (⩽7 years) independent adjusted associations between individual serotypes and mortality following IPD diagnosis using logistic regression and extended Cox proportional hazards models. Of the 1316 cases included in the analysis, 243 [18·5%, 95% confidence interval (CI) 16·4–20·7] died within 30 days of diagnosis. Four serotypes (3, 6A, 9N, 19 F) were significantly associated with overall increased 30-day mortality. Effects were observable only for older adults (⩾60 years). After extension of the window to 12 months and 36 months, one serotype was associated with significantly increased mortality at 12 months (19 F), but no individual serotypes were associated with increased mortality at 36 months. Two serotypes had statistically significant hazard ratios (HR) for longer-term mortality: serotype 1 for reduced mortality (HR 0·51, 95% CI 0·30–0·86) and serotype 9N for increased mortality (HR 2·30, 95% CI 1·29–4·37). The association with serotype 9N was no longer observed after limiting survival analysis to an observation period starting 30 days after diagnosis. This study supports the evidence for associations between serotype and short-term (30-day) mortality following IPD and provides the first evidence for the existence of statistically significant associations between individual serotypes and longer-term variation in mortality following IPD.

We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.

The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.