Carl Snyder was one of the most prominent US monetary economists of the 1920s and 1930s. His pioneering work on constructing the empirical counterparts of the terms in the equation of exchange led him to formulate a 4% monetary growth rule. Snyder is especially apposite because he was on the staff of the New York Federal Reserve Bank. Why, despite his pioneering empirical work and his position as an insider, did Snyder fail to effectively challenge the dominant real bills views of the Federal Reserve (Fed)? A short answer is that he did not possess a convincing version of the quantity theory that attributed the Great Depression to a contraction in the money stock produced by the Fed, as opposed to the dominant real bills view attributing it to the collapse of speculative excess.

Campylobacter spp. are leading bacterial gastroenteritis pathogens. Infections are largely underreported, and the burden of outbreaks may be underestimated. Current strategies of testing as few as one isolate per sample can affect attribution of cases to epidemiologically important sources with high Campylobacter diversity, such as chicken meat. Multiple culture method combinations were utilized to recover and sequence Campylobacter from 45 retail chicken samples purchased across Norwich, UK, selecting up to 48 isolates per sample. Simulations based on resampling were used to assess the impact of Campylobacter sequence type (ST) diversity on outbreak detection. Campylobacter was recovered from 39 samples (87%), although only one sample was positive through all broth, temperature, and plate combinations. Three species were identified (Campylobacter jejuni, Campylobacter coli, and Campylobacter lari), and 33% of samples contained two species. Positive samples contained 1–8 STs. Simulation revealed that up to 87 isolates per sample would be required to detect 95% of the observed ST diversity, and 26 isolates would be required for the average probability of detecting a random theoretical outbreak ST to reach 95%. An optimized culture approach and selecting multiple isolates per sample are essential for more complete Campylobacter recovery to support outbreak investigation and source attribution.

Inhibitory control plays an important role in children’s cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents’ psychopathology are associated with children’s inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children’s behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; Mage = 7.13 years; Rangeage = 4–11 years). Results showed that theta power, which was positively predicted by prenatal SES and was negatively related to children’s externalizing problems, mediated the longitudinal and negative relation between them. ERP amplitudes and latencies did not mediate the longitudinal association between prenatal risk factors (i.e., prenatal SES and maternal psychopathology) and children’s internalizing and externalizing problems. Our findings increase our understanding of the neural pathways linking early risk factors to children’s psychopathology.

OBJECTIVES/GOALS: 48,000,000 people in the U.S. have hearing loss, negatively impacting quality of life and work. Unveiling axon guidance for auditory type II spiral ganglia neurons (SGNs) will aid development of new therapies. I study the role of Eph/Ephrin and planar cell polarity (PCP) signaling during type II SGN turning and outer hair cell (OHC) innervation. METHODS/STUDY POPULATION: This quantitative study was conducted on Efna3 and Vangl2 null mice possessing Neurog1CreERT2 and R26RtdTomato mutations. Spontaneous Cre activity within the Neurogenin1CreERT2 line causes recombination and expression of fluorescent Rosa26 Reporter (R26R)tdTomatoin a restricted number of SGNs, including type IIs. Together, these lines permit SGN sparse labeling. Immunostaining and confocal imaging were used to analyze dsRed in Efna3 and Vangl2 mice and quantify type II SGN turning. In combination, Imaris 3D renderings were used to quantify type II SGN turning, branching, navigation features and temporal effects of EPHRIN-A3-Fc on type IIs via cochlear cultures (a gain-of-function manipulation). For both sexes, 5-6 cochleae per genotype were analyzed and compared by t-test to wildtype (WT) controls. RESULTS/ANTICIPATED RESULTS: Efna3 nulls showed a small rise in type II SGNs incorrectly turning toward the apex at an error rate of 16.0% compared to WTs (n=6; p=0.05). P0 Efna3 nulls had reduced branch number compared to WTs, 4.1 and 7.2, respectively (n=129; p=<0.0001), suggesting EPHRIN-A3 acts as a positive growth cue. In cochlear cultures, EPHRIN-A3-Fc led to type II SGN collapse at E15.5, indicating a repulsive function. However, at P0, EPHRIN-A3-Fc treatment led to type II SGNs with elevated branch numbers compared to Control-Fc treatment: 18.1 and 11.4, respectively (n=116; p=<0.0001). This indicates a positive growth function. At E16.5, EPHRIN-A3 protein immunoreactivity on Deiters’ and pillar cells appears reduced in Vangl2 nulls compared to WT cochleae, suggesting that EPHRIN-A3 acts downstream of PCP signaling. DISCUSSION/SIGNIFICANCE: Results suggest that Eph/Ephrin signaling acts downstream of PCP signaling to mediate type II SGN guidance and EPHRIN-A3 switches its mode of activation. The clinical implications of these findings are that therapeutics targeting EPHRIN-A3 and/or VANGL2 in their given pathways could stimulate new OHC innervation following auditory damage.

OBJECTIVES/GOALS: to investigate the potential impact of grandparental factors and multigenerational epigenetic inheritance on the development of ASD METHODS/STUDY POPULATION: Our study recruited participants from the CHARGE (Child Autism Risks from Genetics and the Environment) study, including grandparents, parents, and children. A questionnaire was used to gather information about the participants’ exposure to environmental factors. Saliva samples werecollected from 349 participants. Newborn dried blood spotsfrom probands and parents are still being collected from the California New born Registry. DNA was extracted from 349 saliva samples from 85 families and subjected to whole genome bisulfite sequencing (WGBS) to analyze DNA methylation. Sequence alignments and bioinformatic analyses will be performed using R packages called DMRichR and Comethyl. RESULTS/ANTICIPATED RESULTS: Sequence alignments and bioinformatic analyses are ongoing, utilizing DMRichR to identify individual genomic loci associated with ASD in each of the three generations and Comethyl to compare correlation patterns between methylation marks and selected variables, including grand parental exposures. New born blood spot collections of parents and probands are ongoing and will be used to identify potential ASD epigenomic signatures that are tissue and life-stage independent. DISCUSSION/SIGNIFICANCE: This research will provide new insights into the increased prevalence and underlying etiology of ASD that should pave the way for future research in the field. DNA Methylation signatures can help create molecular biomarkers which can be used together with behavioral clinical tests for diagnosis of ASD.

OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

To make informed decisions, assessment theorists, researchers, and practitioners can evaluate the overlap among (1) relevant theories, (2) empirical contributions, and (3) best practices. Unfortunately, such a task may seem daunting due to the so-called science-practice gap, which can thwart collaboration among these parties. This paper presents an epistemology for delineating the importance of integrating these three sources of knowledge. We then apply this epistemology to show that our current knowledge of assessment and development topics are well integrated in some places, but still quite lacking in others.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Illite polytype quantification allows the differentiation of diagenetic and detrital illite components. In Paleozoic shales from the Illinois Basin, we observe 3 polytypes: 1Md, 1M and 2M1. 1Md and 1M are of diagenetic origin and 2M1 is of detrital origin. In this paper, we compare experimental X-ray diffraction (XRD) traces with traces calculated using WILDFIRE© and quantify mixtures of all 3 polytypes, adjusting the effects of preferred orientation and overlapping peaks. The broad intensity (“illite hump”) around the illite 003, which is very common in illite from shales, is caused by the presence of 1Md illite and mixing of illite polytypes and is not an artifact of sample preparation or other impurities in the sample. Illite polytype quantification provides a tool to extrapolate the K/Ar age and chemistry of the detrital and diagenetic end-members by analysis of different size fractions containing different proportions of diagenetic and detrital illite polytypes.

End members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas and the interlayer-cation-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names (“Commission”) of the International Mineralogical Association (IMA). The definitions and recommendations presented were approved by the Commission.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence. A random selection of 285 from the 481 participants was selected to measure seroconversion. These sera were tested using an IgG enzyme-linked immunosorbent assay against 10 TORCH pathogens. We found that the seroprevalence of all but three of the 10 TORCH pathogens at enrollment was >30%, except for Bordetella pertussis (3.8%), Treponema pallidum (11.4%), and varicella zoster virus (0.5%). Conversely, very few participants seroconverted during their pregnancy and were herpes simplex virus type 2 (n = 24, 11.2%), parvovirus B19 (n = 14, 6.2%), and rubella (n = 12, 5.1%). For birth outcomes, 88% of the participant had live births and 12% had stillbirths or miscarriage. Cytomegalovirus positivity at enrolment had a statistically significant positive association with a live birth outcome (p = 0.0394). Of the 10 TORCH pathogens tested, none had an association with adverse pregnancy outcome.

This study evaluated the feasibility and safety of a telehealth delivered exercise plus plant-based protein diet in adults with non-alcoholic fatty liver disease (NAFLD). This was a 12-week, randomised controlled feasibility trial including twenty-eight adults aged > 45 years with NAFLD randomised to a home muscle strengthening program (3 d/week) with increased protein intake (target ∼1·2–1·5 g/kg/d) from predominately plant-based sources and behavioural change support (3–4 text messages/week) (Pro-Ex n 14) or usual care (UC, n 14). Feasibility was assessed via retention (≤ 10 % attrition), adherence (exercise ≥ 66 %; recommended daily protein serves ≥ 80 %) and safety (adverse events). Secondary outcomes included macronutrient intake (3 × 24-h records), weight, moderate-to-vigorous physical activity (MVPA) and 30 s sit-to-stand (STS) performance. Study retention was 89 %. Mean exercise adherence (Pro-Ex) was 52 % with one adverse event from 241 sessions. In Pro-Ex, mean daily plant protein serves increased (0·9 to 1·4/d) and animal protein decreased (1·5 to 1·2/d) after 12-weeks, but overall adherence (serves/day) was 32[RD1] % (plant) and 42 % (animal). Relative to UC, Pro-Ex experienced a mean 2·7 (95 % CI: 0·9, 4·4) increase in 30 s STS number, 46-minute (95 % CI: −153, 245) increase in MVPA, 1·7 kg (95 % CI: −3·5, 0·2) decrease in weight, 35·2 g (95 % CI: 11·0, 59·3) increase in protein. In adults with NAFLD a telehealth home exercise and dietary intervention was safe and improved habitual plant and animal protein intake, but overall adherence was modest suggesting more intensive healthcare support may be required.

The coefficient of friction of clay minerals at the micro-scale has generally not been studied due to difficulties in obtaining measurements in a bulk-soil volume undergoing shear at such small scales. Information on friction at the micro-scale may provide insight into grain-scale processes that operate in bulk samples or in natural faults. The objective of this study was to develop a method to measure the microscale friction coefficient of smectites. The experiments described show that the axial atomic force microscopy method can be adapted to easily obtain accurate coefficient of friction (μ) measurements for smectites from force curves involving colloidal probes. The method allows for the measurements to be performed over spatial scales of a few μm, can be carried out under dry conditions or a wide range of aqueous solutions, and requires no calibration beyond making a few microscopic measurements of the probe. This method provides measurements of micro-scale normal and shear forces between minerals, which can be used for a variety of applications such as the study of shear deformation, consolidation, and fault dynamics. Control tests of silica on mica (μ = 0.29±0.02) agree with literature values where limits indicate one standard deviation. Coefficient of friction values for wet and dry Na-montmorillonite were determined to be 0.20±0.03 and 0.72±0.03, respectively.

A new model is proposed for analysis of the source clays used to create ceramics, based on geographic, petrographic, mineralogical, mineral-chemistry, and geochemical criteria. The development of this model became feasible after the discovery of a Pliocene volcanic clay horizon on NWAegina Island, Greece. The volcanic clay contains smectite, mixed-layer chlorite-smectite, biotite, and palygorskite and has greater feldspar content than the underlying Pliocene marls, which contain R0 mixed-layer illitesmectite, mica, dolomite, serpentine, talc and gypsum, and, in some places, palygorskite. The two units have distinct geochemical characteristics. In general the Pliocene volcanic clay is richer in SiO2, Al3O3, and Fe2O3 and poorer in Na2O, MgO, and P2O2 than the Pliocene marls. The Nb, Zr, Hf, Th, and rare earth element (REE) contents are also significantly greater in the Pliocene volcanic clay and comparable to those of the dacitic rocks of the island, reflecting the volcanic origin of the clay.

The proposed model was used to identify the source-clay materials that were used for the production of ceramics on the island of Aegina (Aeginetan Ware). All five criteria should be considered in any provenance study. The use of individual criteria on their own can lead to ambiguous conclusions. In the present study the geochemical criterion was particularly helpful. It provided robust evidence for the nature of the source clay. The Pliocene volcanic clay horizon and the underlying Pliocene marls are the candidate raw materials for Aeginetan Ware. Although the Pliocene marls have been invoked as raw materials for Greek Bronze Age (~3000–1100 BC) Aeginetan ceramics and are used as raw materials by modern Aeginetan ceramists, the geochemical characteristics of a large set of Bronze Age Greek Aeginetan sherds with fine and coarse fabrics coincide with those of the Pliocene volcanic clay. This comparative and cumulative evidence suggests that the Pliocene volcanic clay was the main source clay for ancient Aeginetan ceramics, regardless of the fabric (coarse or fine) and that admixture of different sources might not be necessary for fine-grained ceramics.