It doesn't get much more Japanese than this. The large, white-feathered crested ibis — a wader with a downward- curving bill, a face bare of feathers and bright- red skin and legs — is a worldwide symbol of Japan (though the national bird is the pheasant). The birds grow up to 78 cm long, have a plume of feathers on the back of the head, and the flight feathers are tinged with red, a celebrated feature that was also the cause of their downfall.

Objectives/Goals: We hypothesized that the bulk transcriptomic profiling of blood collected from within the ischemic vasculature during an acute ischemic stroke with large vessel occlusion (LVO) will contain unique biomarkers that are different from the peripheral circulation and may provide much-needed insight into the underlying pathogenesis of LVO in humans. Methods/Study Population: The transcriptomic biomarkers of Inflammation in Large Vessel Ischemic Stroke pilot study prospectively enrolled patients ≥ 18 years of age with an anterior circulation LVO, treated with endovascular thrombectomy (EVT). Two periprocedural arterial blood samples were obtained (DNA/RNA Shield™ tubes, Zymo Research); 1) proximal to the thrombus, from the internal carotid artery and 2) immediately downstream from the thrombus, by puncturing through the thrombus with the microcatheter. Bulk RNA sequencing was performed and differential gene expression was identified using the Wilcoxon signed rank test for paired data, adjusting for age, sex, use of thrombolytics, last known well to EVT, and thrombolysis in cerebral infarction score. Bioinformatic pathway analyses were computed using MCODE and reactome. Results/Anticipated Results: From May to October 2022, 20 patients were screened and 13 were enrolled (median age 68 [SD 10.1], 47% male, 100% white). A total of 608 differentially expressed genes were found to be significant (p-value) Discussion/Significance of Impact: These results provide evidence of significant gene expression changes occurring within the ischemic vasculature of the brain during LVO, which may correlate with larger ischemic infarct volumes and worse functional outcomes at 90 days. Future studies with larger sample sizes are supported by this work.

Autism spectrum disorder is defined by the presence of sustained problems in areas of social cognition and social understanding alongside repetitive and/or restricted patterns of behaviour. Behavioural presentations and developmental trajectories in autism are highly heterogeneous. For most, characteristics variably continue across the lifespan, and, for many, they overlap with numerous overrepresented comorbid combinations spanning behavioural, psychiatric and somatic domains. The current autism diagnostic systems (DSM-5, ICD-11) reflect this heterogeneity, focusing on discerning different assistance needs and symptom severity combinations. An emerging view on the pluralisation of autism – ‘the autisms’ – based on different severity levels and different developmental trajectories is gaining popularity, bolstered by the introduction of the grouping ‘profound autism’ and observations of non-persistence of autism for some. We advance the case for expanding the definition of the plural autisms based also on the numerous different aetiological routes that can lead to autism. Various genetic conditions, susceptibility to infectious agents, non-infectious environmental exposures and immune-mediated occurrences have all been observed to culminate in a diagnosis of autism. As a triad, aetiology, presentation intensity and developmental trajectory offer new ways to classify the autisms, with potentially important implications for research and practice.

In 2015, a continuous 15.4 m snow/firn core was recovered from central South Georgia Island at ∼850 m a.s.l. All firn core samples were analyzed for major (Al, Ca, Mg, Na, K, Ti and Fe) and trace element concentrations (Sr, Cd, Cs, Ba, La, Ce, Pr, Pb, Bi, U, As, Li, S, V, Cr, Mn, Co, Cu and Zn) and stable water isotopes. The chemical and isotopic signal is well preserved in the top 6.2 m of the core. Below this depth, down to the bottom of the core, signal dampening is observed in the majority of the elemental species making it difficult to distinguish a seasonal signal. Thirteen elements (As, Bi, Ca, Cd, Cu, K, Li, Mg, Na, Pb, S, Sr and Zn) have crustal enrichment factor values higher than 10 suggesting sources in addition to those found naturally in the crust. While this study shows that 850 m a.s.l. is not high enough to preserve a record including recent years, higher-elevation (>1250 m a.s.l.) glaciers may be likely candidates for ice core drilling to recover better-preserved, continuous, recent to past glaciochemical records.

Over the last three decades, Australian administrative law decisions about who will be allowed to stay in Australia have led to more interaction and tension between the elected government (Parliament and Ministry) and the judiciary than any other subject matter. This interaction has been intensified by Parliament’s attempts to amend the Migration Act 1958 (Cth) to codify judicial review and the procedures to be followed when making decisions under the Act. These amendments were made with the specific aim of minimising, if not practically eliminating, the judiciary’s influence over executive decision-making. However, this outcome has not been achieved. Rather, through a thousand cuts, or more literally cases, the codification efforts of Parliament have been weakened. Instead, the judiciary has put in place an overarching judicial review framework centred on the inherently flexible concept of jurisdictional error. This framework places equal emphasis on both express and implied statutory obligations and procedures. Express procedures have often being interpreted to include judicially created natural justice-like obligations and implied procedures often including other natural justice-like obligations or at least a base level of fairness premised on the constitutionally entrenched premise that the executive cannot decide arbitrarily.

Synthesising knowledge on the health of marine ecosystems and the human activities is crucial to informing holistic marine management. In many coastal states, however, research is conducted in an ad hoc manner and rarely compiled into accessible repositories making it challenging for marine managers to identify knowledge gaps when allocating resources. Here we conduct a structured review of existing literature to identify the current state of marine and coastal knowledge in the Isles of Scilly, an oceanic archipelago in the UK. The archipelago's marine flora and fauna are biogeographically unique in the Northeast Atlantic, with a distinct mosaic of warm and cold temperate habitats and species and are also considered a rare example of a near pristine marine environment in the otherwise highly degraded Northeast Atlantic Ocean. We found 150 sources relating to the marine biodiversity and relevant human activities in the Isles of Scilly with increasing diversification of research topics in recent years. Sources however remain dominated by specific taxa and habitats, suggesting the Isles of Scilly would particularly benefit from future research into: (1) anthropogenic impacts associated with warming waters and intense seasonal vessel activity; (2) development of repeatable survey protocols that can underpin long-term, ecosystem-based monitoring and management (notably for reef and sediment habitats and the European spiny lobster); and (3) data gaps associated with marine teleost fish and elasmobranch communities including identifying core habitat. This review can therefore act as a baseline biological synthesis for the region and importantly, can inform future research priorities.

OBJECTIVES/GOALS: Estimating kidney function for drug dosing poses safety and efficacy concerns with critical medications. This study aims to develop a pragmatic method for measuring kidney function, ensuring that critical clinical decision points based on kidney function are universally applicable to all patients, leading to improved health outcomes. METHODS/STUDY POPULATION: This is a single-dose pharmacokinetic (PK) study to evaluate the concordance between iopamidol- and iohexol-measured glomerular filtration rate (mGFR), as determined by their respective serum clearances, in a cohort of 24 adults with varying kidney function. Participants with estimated glomerular filtration rates (CKD-EPI eGFRcr) ranging from >30 to 120 mL/min will be recruited from the Michigan Medicine health system. Enrolled participants will be stratified into 3 kidney function groups based on conventual kidney dosing considerations. IV micro doses of iohexol and iopamidol will be administered, followed by blood sampling. PK analysis will be used to compare the clearance of these substances. The agreement between iohexol and iopamidol in measuring GFR will be assessed via bioequivalence analysis. RESULTS/ANTICIPATED RESULTS: We expect no statistically significant difference between iopamidol and iohexol CL due to the high similarity of iopamidol and iohexol molecular and PK properties. We also expect that the ordinary least square regression analysis of iopamidol mGFRand iohexol mGFR will show limited variability across GFR measurements. These expected results will support the use of iopamidol as a marker of mGFR and its interchangeability with the gold standard iohexol. DISCUSSION/SIGNIFICANCE: Addressing eGFR errors is crucial for accurately dosing critical medications. This study aims to develop a novel mGFR methodology that accommodates various kidney function levels. This will enable precision dosing and streamline clinical trials. It also eliminates biological variability, enhancing generalizability and health outcomes.

OBJECTIVES/GOALS: The time between lower extremity amputations and prosthetic acquisition profoundly influences patient rehabilitation and mortality outcomes. Our primary outcome was time to prosthetic acquisition following major limb amputation. We hypothesize that women face an increased time lag between amputation and prosthetic acquisition compared to men. METHODS/STUDY POPULATION: We used the 2015-2021 Truven Marketscan Medicare and Commercial Claims Administrative dataset to identify individuals with lower extremity amputations based on CPT codes. We excluded patients < 18 years old, those with prior/concurrent major extremity amputations, and those with <= 31 days discontinuity in enrollment. To estimate time to prosthetic acquisition after initial amputation, Weibull Accelerated Failure Time multivariable regression models were used to estimate unadjusted and adjusted time ratios and 95% confidence intervals comparing men to women. We adjusted models for age, Medicare supplement/commercial payer, Metropolitan Statistical Area (MSA), amputation type, social deprivation index, and Elixhauser comorbidities. RESULTS/ANTICIPATED RESULTS: We identified 4,054 patients with major lower extremity amputations (75% below knee and 25% at or above knee). Patients were predominantly male (72%). For patients who received prosthetics, 39.06% of men and 31.28% of women received prosthetics within the first three months of amputation (p<0.001). Time ratios > 1 indicated longer time to prosthetic acquisition between comparison groups. The adjusted time ratio for women compared to men for the time to acquisition of prosthetics was increased; this was statistically significant (TR 1.3281, 95% CI 1.1667, 1.5118). This time ratio suggests that if a man received a prosthetic in 100 days, a women would receive her prosthetic in 133 days. DISCUSSION/SIGNIFICANCE: We found a significant difference in the time to prosthetic acquisition following major limb amputation and acquisition rate in the first three months of amputation among men and women. Successful rehabilitation, quality of life, and healthcare costs are influenced by the timeliness of prosthetic acquisition.

The safe disposal of 60Co, 63Ni, and 59Ni has required considerable information on the interactions of Co2+ and Ni2+ with clay minerals in the geosphere. X-ray photoelectron spectroscopy (XPS) has been used to probe the sorption sites for Co2+ and Ni2+ on hectorite and montmorillonite. The spectra were measured for Co-hectorite, Ni-hectorite, and Ni-montmorillonite immediately following ion exchange and after washing the clay two and five times with distilled water. The spectra, recorded following etching of the surface with an argon ion beam, differentiate two sorption sites; a labile (to washing) fraction sorbed as ion pairs, and a non-labile fraction sorbed by ion exchange at broken bond and interlamellar sites. The data were consistent with the sorption of metal ions (Co2+, Ni2+) in a common “MO6” ligand environment.

Co2+ had a greater affinity for exchange on hectorite than did Ni2+; but Ni2+ had a greater affinity for the surface of montmorillonite than for hectorite. The argon ion etching of Ni-montmorillonite gave rise to a new photopeak of 853 eV, which was probably due to elemental Ni formed consequent to the chemical violation of the surface by ion etching.

Although still prevalent in many human societies, the practice of cousin marriage has precipitously declined in populations undergoing rapid demographic and socioeconomic change. However, it is still unclear whether changes in the structure of the marriage pool or changes in the fitness-relevant consequences of cousin marriage more strongly influence the frequency of cousin marriage. Here, we use genealogical data collected by the Tsimane Health and Life History Project to show that there is a small but measurable decline in the frequency of first cross-cousin marriage since the mid-twentieth century. Such changes are linked to concomitant changes in the pool of potential spouses in recent decades. We find only very modest differences in fitness-relevant demographic measures between first cousin and non-cousin marriages. These differences have been diminishing as the Tsimane have become more market integrated. The factors that influence preferences for cousin marriage appear to be less prevalent now than in the past, but cultural inertia might slow the pace of change in marriage norms. Overall, our findings suggest that cultural changes in marriage practices reflect underlying societal changes that shape the pool of potential spouses.

In order to remove impurities, natural illite is often subjected to chemical pretreatments before analysis, the assumption being that such pretreatments have little or no effect on the composition of illite. Bulk analyses are sometimes reported before and after pretreatment (Aja et al. 1991) but, because the contribution of the impurities to the bulk composition is unknown, the possible effects of chemical pretreatments on the composition of illite cannot be assessed. Recently, Rosenberg and Hooper (1996) have shown that analytical transmission electron microscopy (ATEM) techniques, which exclude impurities, can be used to determine the bulk compositions of relatively pure illite by averaging the analyses of at least 50 crystals per sample. This approach can be applied to impure illite in order to determine the effect of chemical pretreatments on the composition of natural illite.

Health systems are integrating medical-legal partnerships (MLPs) into clinical care and increasingly center “complex care” patients. These patients have intersecting medical and social needs and often face systemic inequities that exacerbate their chronic health conditions. This paper describes a role for MLPs in hospital quality initiatives; examines the ethics of MLPs assisting with guardianship and institutionalization of hospital patients including marginalized groups; and advocates for MLP interventions designed to address intersectional and ethical concerns.

This article proposes an interpretive framework of paradox and wonder as a new approach to understanding the affective properties and social consequences of miniature objects in the archaeological record. Building upon current scholarly theories of miniatures as inherently intimate, this approach accounts for how small-scale artworks were also designed and deliberately manufactured to elude user attempts at full sensory access and immersive escapism. This desire-provoking tension between intimacy and distance—which lures viewers into small-scale encounters only to insist upon the object's life-size existence—is wonder, and it is what gives miniature objects their social relevance and ability not only to reflect, but also to influence, the real world. The benefits and applicability of this approach to miniaturization are illustrated through analysis of case studies of miniature objects (figurines, coins, seals and seal impressions, and jewellery) from Hellenistic Babylonia (Seleucid and Parthian periods in southern Mesopotamia, modern Iraq, 323 bce–ce 224).

The coronavirus disease 2019 (COVID-19) pandemic highlighted the lack of agreement regarding the definition of aerosol-generating procedures and potential risk to healthcare personnel. We convened a group of Massachusetts healthcare epidemiologists to develop consensus through expert opinion in an area where broader guidance was lacking at the time.