Objectives/Goals: We have shown that parathyroid hormone-related protein (PTHrP) is enriched at the LIFR promoter in breast cancer cells and inhibits the expression of dormancy-associated genes including LIFR. The objective of this study is to define where all PTHrP binds DNA and identify pathways that are regulated by PTHrP that promote breast cancer colonization of the bone. Methods/Study Population: In this study, we use human estrogen receptor-positive MCF7 breast cancer cells which we and others have reported lie dormant in the bone. MCF7 cells were engineered to express either PTHrP with an HA-tag (MCF7P), or a vector control (MCF7V). We use Cleavage Under Targets and Release Using Nuclease (CUT&RUN), a method of mapping protein-DNA interactions, to define where PTHrP binds DNA. Here, an HA-specific antibody identifies regions of DNA that are bound to PTHrP in MCF7P cells compared to MCFV cells. Next, we perform DNA sequencing and gene set enrichment analysis (GSEA) on genes identified by CUT&RUN to identify pathways that are regulated by PTHrP. These experiments will determine how PTHrP regulates dormancy and breast cancer colonization in the bone. Results/Anticipated Results: We completed IgG (-control), H3K4me3 (+ control), and HA (PTHrP) CUT&RUN on MCF7V and MCF7P cells, and submitted DNA for sequencing. This study will define where PTHrP binds the genome and identify pathways regulated by PTHrP. Previously, through ChIP-qPCR we showed that PTHrP binds the LIFR promoter to repress LIFR expression. Given this result, we expect that PTHrP binds to the promoters of dormancy-associated genes including LIFR in MCF7P cells compared to MCF7V cells. PTHrP may be involved in regulating other processes besides dormancy to induce expansion of breast cancer cells in the bone, so we will use GSEA to identify pathways that are altered in MCF7P cells when PTHrP is over-expressed compared to MCF7V cells. Together, this will define how PTHrP regulates gene expression of bone metastatic breast cancer cells. Discussion/Significance of Impact: This study will unveil mechanisms of metastatic breast cancer expansion in the bone by defining where PTHrP binds the genome to regulate gene expression. These findings will reveal therapeutic vulnerabilities that will be used to target bone-disseminated tumor cells to prevent lethal recurrence.

Metabolite supplementation during in vitro embryo development improves blastocyst quality, however, our understanding of the incorporation of metabolites during in vitro maturation (IVM) is limited. Two important metabolites, follistatin and choline, have beneficial impacts during in vitro culture; however, effects of supplementation during IVM are unknown. The objective of this study was to investigate combining choline and follistatin during IVM on bovine oocytes and subsequent early embryonic development. We hypothesized that supplementation of choline with follistatin would synergistically improve oocyte quality and subsequent early embryonic development. Small follicles were aspirated from slaughterhouse ovaries to obtain cumulus oocyte complexes for IVM with choline (0, 1.3 or 1.8 mM) and follistatin (0 or 10 ng/mL) supplementation in a 3 × 2 design. A subset of oocytes underwent transcriptomic analysis, the remaining oocytes were used for IVF and in vitro culture (IVC). Transcript abundance of CEPT1 tended to be reduced in oocytes supplemented with 1.8 mM choline and follistatin compared to control oocytes (P = 0.07). Combination of follistatin with 1.8 mM choline supplementation during maturation, tended (P = 0.08) to reduce CPEB4 in oocytes. In the blastocysts, HDCA8, NANOG, SAV1 and SOX2 were increased with choline 1.8 mM supplementation without follistatin (P < 0.05), while HDCA8 and SOX2 were increased when follistatin was incorporated (P < 0.05). The combination of choline and follistatin during oocyte maturation may provide a beneficial impact on early embryonic development. Further research is warranted to investigate the interaction between these two metabolites during early embryonic development and long-term influence on fetal development.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Long-term sequelae of severe acute respiratory coronavirus-2 (SARS-CoV-2) infection may include increased incidence of diabetes. Here we describe the temporal relationship between new type 2 diabetes and SARS-CoV-2 infection in a nationwide database. We found that while the proportion of newly diagnosed type 2 diabetes increased during the acute period of SARS-CoV-2 infection, the mean proportion of new diabetes cases in the 6 months post-infection was about 83% lower than the 6 months preinfection. These results underscore the need for further investigation to understand the timing of new diabetes after COVID-19, etiology, screening, and treatment strategies.

Background: Over the past decade, the CLSI has updated susceptibility break points for several antimicrobial agents. The purpose of this study was to evaluate the impact of these changes against gram-negative bacteria at our academic medical center. Methods: In this retrospective, IRB-approved study, we collected consecutive, nonduplicate clinical isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, and Pseudomonas aeruginosa for the past decade (2010–2019) at our academic medical center and 3 adult ICUs. Susceptibility testing was performed using the BD Phoenix automated system. For these isolates, susceptibilities for 7 β-lactams (aztreonam, ceftriaxone, ceftazidime, cefepime, piperacillin/tazobactam, ertapenem, and meropenem) and 2 fluoroquinolones (levofloxacin, ciprofloxacin) were calculated based upon CLSI break points in 2010 and current CLSI break points in 2020. Any change >5% in susceptibility was deemed significant for this analysis. Results: In 17.5% of Enterobacteriales isolates tested, at least 1 antimicrobial demonstrated significant decline. Ertapenem was the most commonly affected antimicrobial (45% of the isolates) followed by ceftriaxone (35%) and cefepime (25%). Susceptibilities of aztreonam, ceftazidime, and meropenem were not affected for any of the Enterobacteriales. The most common organism demonstrating a significant impact on change in susceptibility among the Enterobacteriales was E. cloacae (41.7% of the time) followed by E. aerogenes (20.8%), K. oxytoca (12.5%), K. pneumoniae (8.3%) and E. coli (4.2%). Most of the impact was observed hospital-wide (33.3%), followed closely by the MICU (28.6%), the NSICU (23.8%) and the CVICU (14.3%). For P. aeruginosa, the impact of the antimicrobial break-point changes on susceptibility was more pronounced than the Enterobacteriales. Overall, 93.8% of the time there was a significant decline in antimicrobial susceptibility. Each antimicrobial (ciprofloxacin, levofloxacin, meropenem, and piperacillin/tazobactam) demonstrated a significant decline in susceptibility hospital-wide and in each ICU except for the susceptibility of meropenem in the NSICU. Conclusions: Changes in break points had a significant impact on the susceptibility of all antimicrobials for P. aeruginosa at our institution, both hospital-wide and in the adult ICUs. Although the impact was less for the Enterobacteriales, ertapenem, ceftriaxone, and cefepime demonstrated significant susceptibility changes, especially with E. cloacae. Understanding and evaluating the impact of the break-point changes may lead to changes in empiric therapy in other institutions.

Funding: No

Disclosures: None

Wholegrain consumption is linked to a lower risk of cardiovascular disease. Evidence from randomized controlled trials have established that the consumption of wholegrain oats lowers blood cholesterol, via a mechanism partly mediated by β-glucan soluble fiber. However, oats contain an array of phenolic acids, including ferulic acid and also structurally related avenanthramides, which may also contribute to the cardiovascular health benefits of oat intake. We investigated whether 4 weeks, daily consumption of oat phenolics leads to improvement in markers of CVD risk men and women.In a 3 arm crossover single-blind, placebo-controlled trial, 28 volunteers consumed either: 1) oatmeal/oatcake intervention (-containing 48.9 mg of phenolic acids and 19.2 mg of avenanthramides); 2) oatbran concentrate + rice porridge/wheat cracker intervention (-containing 38.4 mg of phenolic acids and 0.5 mg of avenanthramides) or 3) rice porridge/wheat cracker intervention (containing 13.8 mg of phenolic acids). All treatments were matched in soluble fiber (4.8g) and energy (500kcal). The primary endpoint was FMD and other cardiovascular endpoints were blood pressure, LDI, LDL/HDL cholesterol, platelets and endothelial cell-derived extracellular vesicles (EVs). All measures were taken at baseline and after three, 4 week long intervention periods and two washout periods.Our data indicates an increase by 1.09 % ± 0.41 %(Mean ± SEM) in FMD response following high phenolic oat intake with a significant difference (P = 0.007) between baseline and post-intervention. Consumption of high phenolic oats also led to a significant improvement in 24-hour SBP, day time SBP and night time SBP (P < 0.01, P < 0.01 and P < 0.05) and day time and night time DBP (p < 0.05). There was also a significant decrease with total and LDL cholesterol after the consumption of moderate and high phenolic oat interventions (P < 0.05) and a small improvement in LDI (both Ach and SNP) but not significant. The number of resting endothelial EVs were also found to be increasing after the consumption of high phenolic oats.The findings of this study may provide evidence about the role of oat phenolic acids and avenanthramides in cardiovascular health and contribute to more effective public health advice about the consumption of oats and healthy cardiovascular aging.

Extra-care housing (ECH) has been hailed as a potential solution to some of the problems associated with traditional forms of social care, since it allows older people to live independently, while also having access to care and support if required. However, little longitudinal research has focused on the experiences of residents living in ECH, particularly in recent years. This paper reports on a longitudinal study of four ECH schemes in the United Kingdom. Older residents living in ECH were interviewed four times over a two-year period to examine how changes in their care needs were encountered and negotiated by care workers, managers and residents themselves. This paper focuses on how residents managed their own changing care needs within the context of ECH. Drawing upon theories of the third and fourth age, the paper makes two arguments. First, that transitions across the boundary between the third and fourth age are not always straightforward or irreversible and, moreover, can sometimes be resisted, planned-for and managed by older people. Second, that operational practices within ECH schemes can function to facilitate or impede residents’ attempts to manage this boundary.

The excellent fossil record of the past few million years, combined with the overwhelming similarity of the biota to extant species, provides an outstanding opportunity for understanding paleoecological and macroevolutionary patterns and processes within a rigorous biological framework. Unfortunately, this potential has not been fully exploited because of lack of well-sampled time series and adequate statistical analysis. Nevertheless, four basic patterns appear to be of general significance. First, a major pulse of extinction occurred 1–2 m.y. ago in many ocean basins, more or less coincident with the intensification of glaciation in the Northern Hemisphere. Rates of origination also increased greatly but were more variable in magnitude and timing. The fine-scale correlation of these evolutionary events with changes in climate is poorly understood. Similar events probably occurred on land but have not been tested adequately. Second, rates of origination and extinction in the oceans waned after the pulse of extinction, especially during the past 1 m.y. Thus, most marine species originated long before the Pleistocene under very different environmental circumstances, suggesting that they are “exapted” rather than adapted to their present ecological circumstances. The same may be true for many terrestrial groups, but not for the mammals or fresh-water fishes that have continued to undergo speciation throughout the Pleistocene. Third, community membership of late Pleistocene coral reef communities was more stable than expected by chance. These are the only paleoecological data adequate to test hypotheses of community stability, so that we do not know whether community structure involving other taxa or environments typically reflects more than the collective behavior of individual species distributions. Regardless, the strong evidence for nearly universal exaptation of ecological characteristics argues strongly against ideas of coevolution of species in communities. Finally, ecological communities were profoundly altered by human activities long before modern ecological studies began. Holocene paleontological, archeological, and historical data constitute the only ecological baseline for “pristine” ecological communities before significant human disturbance. Holocene records should be much more extensively used as a baseline for Recent ecological studies and for conservation and management.

Objectives: Apathy is a debilitating symptom of Huntington’s disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington’s disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462–469)

Starbursts are finite periods of intense star formation (SF) that can dramatically impact the evolutionary state of a galaxy. Recent results suggest that starbursts in dwarf galaxies last longer and are distributed over more of the galaxy than previously thought, with star formation efficiencies (SFEs) comparable to spiral galaxies, much higher than those typical of non-bursting dwarfs. This difference might be explainable if the starburst mode is externally triggered by gravitational interactions with other nearby systems. We present new, sensitive neutral hydrogen observations of 18 starburst dwarf galaxies, which are part of the STARburst IRregular Dwarf Survey (STARBIRDS) and each were mapped with the Green Bank Telescope (GBT) and/or Parkes Telescope in order to study the low surface brightness gas distributions, a common tracer for tidal interactions.

The objective of the present study was to evaluate intakes and serum levels of vitamin A, vitamin E, and related compounds in a cohort of maternal–infant pairs in the Midwestern USA in relation to measures of health disparities. Concentrations of carotenoids and tocopherols in maternal serum were measured using HPLC and measures of socio-economic status, including food security and food desert residence, were obtained in 180 mothers upon admission to a Midwestern Academic Medical Center labour and delivery unit. The Kruskal–Wallis and independent-samples t tests were used to compare measures between groups; logistic regression models were used to adjust for relevant confounders. P < 0·05 was considered statistically significant. The odds of vitamin A insufficiency/deficiency were 2·17 times higher for non-whites when compared with whites (95 % CI 1·16, 4·05; P = 0·01) after adjustment for relevant confounders. Similarly, the odds of being vitamin E deficient were 3·52 times higher for non-whites (95 % CI 1·51, 8·10; P = 0·003). Those with public health insurance had lower serum lutein concentrations compared with those with private health insurance (P = 0·05), and living in a food desert was associated with lower serum concentrations of β-carotene (P = 0·02), after adjustment for confounders. Subjects with low/marginal food security had higher serum levels of lutein and β-cryptoxanthin compared with those with high food security (P = 0·004 and 0·02 for lutein and β-cryptoxanthin). Diet quality may be a public health concern in economically disadvantaged populations of industrialised societies leading to nutritional disadvantages as well.

In October 2014, flyers appeared in mailboxes of Montana voters that positioned nominees for the state Supreme Court according to an ideological scale. The study, authored by researchers from Stanford and Dartmouth, was met with public outrage. The Commissioner of Political Practices in Montana asked me to vet the ethics of the study. The investigation led me to conclude that current Institutional Review Board (IRB) practices are inadequate for evaluating research involving field experiments in political science because there is no explicit attention in the process to protect a community. I believe the IRB should mandate that researchers explicitly address implications about how their research could affect the communities they study.

Objectives: Huntington’s disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis. Methods: The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements. Results: Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning. Conclusions: Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159–170)

Recent changes along the margins of the Antarctic Peninsula, such as the collapse of the Wilkins Ice Shelf, have highlighted the effects of climatic warming on the Antarctic Peninsula Ice Sheet (APIS). However, such changes must be viewed in a long-term (millennial-scale) context if we are to understand their significance for future stability of the Antarctic ice sheets. To address this, we present nine new cosmogenic 10Be exposure ages from sites on NW Alexander Island and Rothschild Island (adjacent to the Wilkins Ice Shelf) that provide constraints on the timing of thinning of the Alexander Island ice cap since the last glacial maximum. All but one of the 10Be ages are in the range 10.2–21.7 ka, showing a general trend of progressive ice-sheet thinning since at least 22 ka until 10 ka. The data also provide a minimum estimate (490 m) for ice-cap thickness on NW Alexander Island at the last glacial maximum. Cosmogenic 3He ages from a rare occurrence of mantle xenoliths on Rothschild Island yield variable ages up to 46 ka, probably reflecting exhumation by periglacial processes.

Field studies were conducted in 1998 and 1999 to evaluate crop response, weed control, Glycine max yield, and economic returns with sulfentrazone alone and tank-mixed with glyphosate, cloransulam, or chlorimuron at two preplant application timings in no-till, narrow-row, glyphosate-resistant G. max. No significant crop injury was observed. Setaria faberi and Polygonum pensylvanicum control 5 wk after planting (WAP) was generally greater with sulfentrazone applied early preplant (EPP) than with sulfentrazone applied at planting (AP). When applied AP, glyphosate plus sulfentrazone provided greater S. faberi control than sulfentrazone alone. Control of Amaranthus rudis, Ambrosia artemisiifolia, and Ipomoea hederacea was greater in 1998 than in 1999 because of more timely early-season precipitation. Sulfentrazone-based programs provided 80 to 100% control of A. rudis in 1998, but control in 1999 ranged from 72 to 95% at Columbia and 46 to 83% at Novelty. Cloransulam alone, at either application timing, was the only treatment that provided greater than 80% control of A. artemisiifolia at each site in each year. All sulfentrazone-based treatments provided greater than 80% control of I. hederacea in 1998, but control was less in 1999 and ranged from 54 to 91%. Xanthium strumarium control ranged from 5 to 94% with sulfentrazone alone; however, the addition of cloransulam or chlorimuron provided 75 to 99% control regardless of application timing. A blanket application of glyphosate was made 6 WAP over all preplant herbicide treatments, and weed control 5 wk after this treatment was greater than 79% with all sulfentrazone-based treatments. Sulfentrazone plus cloransulam or chlorimuron plus glyphosate EPP or AP followed by (fb) glyphosate postemergence (POST) generally provided the greatest weed control. Overall weed control was generally greater with the use of residual herbicides vs. glyphosate alone, although yield and net returns were not always greater. A greenhouse study was conducted to determine if altering the preplant application timing reduced sulfentrazone injury to G. max. Treatment variables included herbicide rate, temperature during a preplant incubation period, and application timing. Glycine max, Zea mays, and Sorghum bicolor were used as indicator species. Sulfentrazone caused less injury to G. max, Z. mays, and S. bicolor in soils incubated at 30 C when applied 20 d before planting compared to 0 d before planting. Equivalent amounts of crop injury were noted with sulfentrazone applied 20 or 0 d before planting in soils incubated at 5 C with all indicator species.

Field studies were conducted in 1998 and 1999 to evaluate crop response, weed control, Glycine max yield, and economic returns of labeled (1×) and one-half labeled (½×) rates of early preplant (EPP) sulfentrazone plus chlorimuron and postemergence glyphosate, compared to glyphosate-alone systems in no-till, narrow-row, glyphosate-resistant G. max. Treatments containing a 1× or ½× rate of EPP sulfentrazone plus chlorimuron with glyphosate followed by (fb) a postemergence treatment of glyphosate provided 80 to 100% control of Xanthium strumarium, Ambrosia artemisiifolia, and Polygonum pensylvanicum and 82 to 100% control of Setaria faberi and Amaranthus rudis if glyphosate was applied mid-postemergence (MPOST) or late postemergence (LPOST). Glyphosate alone EPP fb glyphosate postemergence or sequential postemergence treatments of glyphosate provided 77 to 100% control of S. faberi, A. artemisiifolia, and P. pensylvanicum. Glycine max yield did not significantly differ between treatments that contained 1× or ½× rates of sulfentrazone plus chlorimuron EPP with postemergence glyphosate or sequential glyphosate. Residual herbicides fb glyphosate reduced overall weed control variability but did not reduce the overall yield variability compared to glyphosate alone. Greater weed control, G. max yield, net incomes, and lower coefficient of variation (CV) of net incomes were generally associated with treatments that included both EPP and postemergence treatments vs. single herbicide applications. A greenhouse study was conducted to determine the optimal spray additive to maximize the foliar activity of sulfentrazone on three annual weeds. Sulfentrazone alone and in combination with a nonionic surfactant (NIS), methylated seed oil (MSO), crop oil concentrate (COC), and a silicone-based surfactant (SBS), with and without ammonium sulfate (AMS), were applied on two sizes of Abutilon theophrasti, P. pensylvanicum, and S. faberi. AMS provided little additional efficacy of sulfentrazone on S. faberi, but improved efficacy on A. theophrasti and P. pensylvanicum. SBS or MSO plus AMS with sulfentrazone generally provided the greatest efficacy on all species.

The late Neogene was a time of major environmental change in Tropical America. Global cooling and associated oceanographic reorganization and the onset and intensification of glaciation in the Northern Hemisphere during the past ten million years coincided with the uplift of the Central American isthmus and resulting changes in regional oceanographic conditions. Previous analyses of patterns of taxonomic turnover and the shifting abundances of major ecological guilds indicated that the regional shallow-water marine biota responded to these environmental changes through extinction and via a restructuring of local benthic food webs, but it is not clear whether this ecological response had an effect on the diversity of molluscan assemblages in the region. Changes in regional and local diversity are often used as proxies for similar ecological response to environmental change in large-scale paleontological studies, but a clear relationship between diversity and ecological function has rarely been demonstrated in marine systems dominated by mollusks. To explore this relationship, we have compiled a data set of the stratigraphic and environmental distribution of genera of mollusks in large new collections of fossil specimens from the late Neogene and Recent of the southwestern Caribbean. Analysis of a selection of ecological diversity measures indicates that within shelf depths, assemblages from deeper water (51–200 m) were more diverse than shallow-water (<50 m) assemblages in the Pliocene. Lower diversity for shallow-water assemblages is caused by increased dominance of a few superabundant taxa in each assemblage. This implies that studies of diversity of shelf benthos need to control for relatively fine scaled environmental conditions if they are to avoid interpreting artifacts of uneven sampling as true change of diversity. For shallow-water assemblages only, there was significant increase in local and regional diversity of bivalve assemblages after the late Pliocene. No parallel increase in gastropods could be detected, but this likely is because sample size was inadequate for documenting the diversity of gastropod assemblages following a steep post-Pliocene decline of average gastropod abundance. Both the increasing bivalve diversity and the decrease in average abundance of gastropod taxa correspond to an interval of increasing carbonate deposition and reef building in the region, and are likely a result of increased fine-scale habitat heterogeneity controlled by the local distribution of carbonate buildups. Each of these results demonstrates that documenting the ecological response of tropical marine ecosystems to regional environmental change requires a large volume of fine-scaled samples with detailed paleoenvironmental control. Such data sets are rarely available from the fossil record.

Federal housing policy reveals an unexpected political cycle of Republican innovation and Democratic appropriation. The political trajectory of rental housing vouchers since their inception reveals a partisan policy cycle. Vouchers were originally proposed as a Republican alternative to Democratic public housing construction and slowly emerged as a viable component of housing policy in the United States. In the mid-1990s, a shift occurred in which Democrats embraced vouchers and Republicans retreated from their innovation. This article suggests a partisanship model of policy making that both challenges and supplements conventional models of the policy process.