Geotechnical drilling for a tunnel between Port Moody and Burnaby, BC, Canada, uncovered a buried fjord. Its sedimentary fill has a thickness of at least 130 m and extends more than 37 m below present mean sea level. Recovered sediments record cyclical growth and decay of successive Cordilleran ice sheets. The oldest sediments comprise 58 m of almost stoneless silt conformably overlying ice-proximal sediments and till, which in turn overlie bedrock. These sediments may predate Marine Isotope Stage (MIS) 4. Glacial sediments assigned to MIS 4 overlie this basal succession and, in turn, are overlain by MIS 3 interstadial sediments and sediments from two MIS 2 glacial advances. Indicators of relative sea-level elevations that bracket glacial deposits of MIS 4 and 2 indicate the cyclic existence of moat-like isostatic depressions in the front of expanding ice sheets. Compared with present sea level, these depressions were at least 160 m during the onsets of MIS 4 and MIS 2. Assuming a maximum eustatic drawdown of 120 m during MIS 2, isostatic depression may have exceeded 200 m during retreat of glacial ice from the Evergreen tunnel area. This is consistent with region-specific low mantle viscosity and rapid Cordilleran Ice Sheet buildup and wasting.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

In psychoanalytic theory, the notion of the person inevitably evokes the notion of subjectivity. Not that the former can be reduced to the latter; but if psychoanalytic theory is anything more a certain type of therapeutic practice, it is indeed a theory of the subject or a theory of the subjective relation. We should perhaps begin by specifying that the subjective relation must be understood as a complex whole: an intrapsychic relation, that is, a relation between the various instances that make up the subject, and at the same time an inter subjective relation, that is, a relation between (at least) two subjects. These two aspects are both inseparable and conflictual. They are inseparable because the self cannot exist, cannot construct itself without the other (whether this be a parental other or a peer). They are conflictual for at least two reasons. On the one hand, because the intrapsychic relation is by definition an arena of conflict: the conflict that opposes the Ego to the contradictory but equally tyrannical demands of the Id - which translates its attachment to the body and testifies to its inherent drives - and of the Superego, which represents its rootedness in the social and cultural sphere. And on the other hand, because this subject, which is thus divided within itself, must undergo the trial of bringing its desire face to face with the desire of the others with whom it is destined to live. The psychoanalytic theory of the subject is therefore the theory of a doubly heterogeneous relation: there is the heterogeneity of the components of the self, which go, once again, from their anchorage in somatic drives to the most ethereal expressions of the ideal; and there is the heterogeneity of the relation between this self and the self of the other. Moreover, this double heterogeneity is not limited to the matter of components: after all, these, one might think, would ideally be open to reabsorption into the homogeneity of the individual. On the contrary, this heterogeneity gives rise to a double rationality or double logic. Psychic causality - to borrow André Green's expression - is also driven by the conflict that opposes what in psychoanalysis are known as the primary processes, which Freud has described in chapter 7 of the Traumdeutung and which govern the formation and organization of the dream images, to the secondary processes, which are those processes that govern our daytime thoughts. Psychic causality is formed by the struggle for hegemony between these two logics, each of which is itself acted upon by an antagonism between what Freud, at the end of his life, called Eros and Thanatos, the urge for Life and the drive toward death or destruction.

OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.

The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with $\sim$ 15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination $+41^\circ$ made over a 288-MHz band centred at 887.5 MHz.

The use of cluster robust standard errors (CRSE) is common as data are often collected from units, such as cities, states or countries, with multiple observations per unit. There is considerable discussion of how best to estimate standard errors and confidence intervals when using CRSE (Harden 2011; Imbens and Kolesár 2016; MacKinnon and Webb 2017; Esarey and Menger 2019). Extensive simulations in this literature and here show that CRSE seriously underestimate coefficient standard errors and their associated confidence intervals, particularly with a small number of clusters and when there is little within cluster variation in the explanatory variables. These same simulations show that a method developed here provides more reliable estimates of coefficient standard errors. They underestimate confidence intervals for tests of individual and sets of coefficients in extreme conditions, but by far less than do CRSE. Simulations also show that this method produces more accurate standard error and confidence interval estimates than bootstrapping, which is often recommended as an alternative to CRSE.

The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.

In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.

The symposium develops statistical models and methods for the study of path dependence. In this introductory essay, the connections between key areas in the path dependence and statistical literatures are illuminated. And some ways in which familiar time series and regression models embody these ideas are explained. The arguments in the articles in the symposium then are summarized and compared. Finally, directions for additional, statistically grounded research on path dependence are discussed.

This article presents a statistical model of the survey response that includes both a measure of the respondent's likely true attitude and a measure of the probability that the respondent is uncertain about her or his attitude and is “guessing” at a response. This latter possibility introduces systematic measurement error that may bias efforts to get unbiased estimates of attitudes. The model and the likely consequences of guessing are illustrated with questions about Vietnam policy taken from the 1968, 1970, and 1972 National Election Studies (NES) surveys. The article ends with a discussion of the limitations and fragility of the model.

Path dependence is commonly used to describe processes where “history matters,” which encompasses many different kinds of temporal dynamics. This essay distinguishes path-, or equilibrium-, dependent processes where early conditions continue to matter, from outcome-dependent processes where recent history matters and from outcome-independent processes where history does not matter. Others have argued for a precise and restrictive definition of path dependence. We build on this and distinguish among different types of outcome-dependent processes when these conditions for path dependence are not fully satisfied.

The ordinary least squares (OLS) estimator gives biased coefficient estimates if coefficients are not constant for all cases but vary systematically with the explanatory variables. This article discusses several different ways to estimate models with systematically and randomly varying coefficients using estimated generalized least squares and maximum likelihood procedures. A Monte Carlo simulation of the different methods is presented to illustrate their use and to contrast their results to the biased results obtained with ordinary least squares. Several applications of the methods are discussed and one is presented in detail. The conclusion is that, in situations with variables coefficients, these methods offer relatively easy means for overcoming the problems.

Many important social science models are estimated with subnational units, such as states, congressional districts, or counties as the units of observation. These analyses may require estimates of population characteristics for these units that are not readily available from published sources. Frequently the size and number of these units make direct data collection, such as household surveys, prohibitively expensive or completely infeasible. The need is to develop methods for using more readily available data to estimate these subgroup attributes. This article presents such a method based on national-level survey data.

This paper extends models of micro- and macropartisanship in two ways. It first develops a model of individual partisanship that accommodates changes in partisan utilities. Achen's Bayesian partisan updating is a special case of our model. This more general micromodel is then aggregated to create a model of macropartisanship. This macromodel is a more general version of the models of macropartisanship estimated by various authors. The less restricted version incorporates possible individual and temporal heterogeneity. We present an example using real data that offers a possible way to estimate the parameters in the full aggregate model.

This paper develops an estimator for models of election returns in multiparty elections. It shares the same functional formas the Katz—King estimator but is computationally simpler, can be used with any number of parties, and is based on more conventional distributional assumptions. Small sample properties of the estimator are derived, which makes it particularly useful in many of the applications where there are a relatively small number of voting districts. The distributional assumptions are contained in two elements. The first treats the observed votes as the outcomes resulting from sampling the voters in each district. The second stochastic element arises from the usual treatment of the stochastic term in a regression model, namely, the inability of the included variables and the linear form to match the underlying process perfectly. The model is then used to analyze the 1993 Polish parliamentary elections. The results from this analysis are used to develop Monte Carlo experiments comparing several different yet feasible estimators. The conclusion is that a number of accessible estimators, including the standard seemingly unrelated regression model and the Beck-Katz model with panel-corrected standard errors, are all good choices.

The fossil record displays remarkable stasis in many species over long time periods, yet studies of extant populations often reveal rapid phenotypic evolution and genetic differentiation among populations. Recent advances in our understanding of the fossil record and in population genetics and evolutionary ecology point to the complex geographic structure of species being fundamental to resolution of how taxa can commonly exhibit both short-term evolutionary dynamics and long-term stasis.