The single largest contributor to human mortality is cardiovascular disease, the top risk factor for which is hypertension (HTN). The last two decades have placed much emphasis on the identification of genetic factors contributing to HTN. As a result, over 1,500 genetic alleles have been associated with human HTN. Mapping studies using genetic models of HTN have yielded hundreds of blood pressure (BP) loci but their individual effects on BP are minor, which limits opportunities to target them in the clinic. The value of collecting genome-wide association data is evident in ongoing research, which is beginning to utilize these data at individual-level genetic disparities combined with artificial intelligence (AI) strategies to develop a polygenic risk score (PRS) for the prediction of HTN. However, PRS alone may or may not be sufficient to account for the incidence and progression of HTN because genetics is responsible for <30% of the risk factors influencing the etiology of HTN pathogenesis. Therefore, integrating data from other nongenetic factors influencing BP regulation will be important to enhance the power of PRS. One such factor is the composition of gut microbiota, which constitute a more recently discovered important contributor to HTN. Studies to-date have clearly demonstrated that the transition from normal BP homeostasis to a state of elevated BP is linked to compositional changes in gut microbiota and its interaction with the host. Here, we first document evidence from studies on gut dysbiosis in animal models and patients with HTN followed by a discussion on the prospects of using microbiota data to develop a metagenomic risk score (MRS) for HTN to be combined with PRS and a clinical risk score (CRS). Finally, we propose that integrating AI to learn from the combined PRS, MRS and CRS may further enhance predictive power for the susceptibility and progression of HTN.

While conservation practices promote soil health and reduce the negative environmental effects from agricultural production, their adoption rates are generally low. To facilitate farmer adoption, we carried out a survey to identify potential challenges faced by farmers regarding conservation tillage and cover crop adoption in the western margin of the US Corn Belt. We found farmers' top two concerns regarding conservation tillage were delayed planting, caused by slow soil warming in spring, and increased dependence on herbicide and fungicides. Narrow planting window and lack of time/labor were perceived by farmers as the two primary challenges for cover crop adoption. Some sense of place factors, including the commonly included dimensions of attachment, identity and dependence, played a role in farmers' perceived challenges. For example, respondents more economically dependent on farming perceived greater challenges. We found that farmers' challenge perceptions regarding reduced yield and lack of time/labor significantly decreased as years of usage increased, implying that time and experience could dilute some challenges faced by farmers. Our findings indicate that social network use, technical guidance and economic subsidies are likely to address the concerns of farmers and facilitate their adoption of conservation practices.

The Singhbhum Shear Zone in eastern India hosts several Fe oxide–Cu–Au (IOCG)-type polymetallic deposits, mined primarily for U, Cu and apatite, with elevated concentrations of rare earth elements, Ni, Co, Mo, Te and Au in association with low-Ti magnetite. Although the main stages of hydrothermal U, Cu and rare earth element mineralization are known to be Palaeoproterozoic in age, the age of shear deformation in the host shear zone has hitherto not been constrained. Here, we report Re–Os ages of syn-shearing massive molybdenite occurring along shear surfaces transecting the uranium ores in the Jaduguda uranium deposit. Integrating the obtained Re–Os age of c. 1.64–1.59 Ga of molybdenite, the known ages of mineralization and the known tectonothermal events in the adjoining Proterozoic Mobile Belt, we propose that the main stages of polymetallic hydrothermal mineralization pre-dated the pervasive shear deformation event in the Singhbhum Shear Zone. We further suggest that the shear zone was not the principal foci of the hydrothermal mineralization of the main stages. Instead, the shear zone was localized during the Palaeoproterozoic to Mesoproterozoic transition (c. 1.64–1.59 Ga) along pre-existing crustal-scale extensional faults which had earlier been the foci of hydrothermal alteration and mineralization in Palaeoproterozoic time (c. 1.9–1.8 Ga). Shear deformation and metamorphism have reconstituted/redistributed existing mineral/metal inventories with/without neo-mineralization.

We present the case of a 4-month-old, former 23-week premature baby who underwent patent ductus arteriosus device closure in the cardiac catheterisation lab with an Amplatzer Piccolo™ device at 12 weeks of life. This was complicated by late migration of the device into the aorta resulting in severe obstruction and requiring surgical intervention.

ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load <50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p<0.001 and cluster threshold of p<0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p<0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p<0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.

This paper describes a computational investigation of multimode instability growth and multimaterial mixing induced by multiple shock waves in a high-energy-density (HED) environment, where pressures exceed 1 Mbar. The simulations are based on a series of experiments performed at the National Ignition Facility (NIF) and designed as an HED analogue of non-HED shock-tube studies of the Richtmyer–Meshkov instability and turbulent mixing. A three-dimensional computational modelling framework is presented. It treats many complications absent from canonical non-HED shock-tube flows, including distinct ion and free-electron internal energies, non-ideal equations of state, radiation transport and plasma-state mass diffusivities, viscosities and thermal conductivities. The simulations are tuned to the available NIF data, and traditional statistical quantities of turbulence are analysed. Integrated measures of turbulent kinetic energy and enstrophy both increase by over an order of magnitude due to reshock. Large contributions to enstrophy production during reshock are seen from both the baroclinic source and enstrophy–dilatation terms, highlighting the significance of fluid compressibility in the HED regime. Dimensional analysis reveals that Reynolds numbers and diffusive Péclet numbers in the HED flow are similar to those in a canonical non-HED analogue, but conductive Péclet numbers are much smaller in the HED flow due to efficient thermal conduction by free electrons. It is shown that the mechanism of electron thermal conduction significantly softens local spanwise gradients of both temperature and density, which causes a minor but non-negligible decrease in enstrophy production and small-scale mixing relative to a flow without this mechanism.

OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.

Advocating for good physical healthcare for their patients is of the utmost importance to psychiatrists. This narrative review focuses on one part of this large goal, the topic of hyperprolactinaemia from the perspective of mental healthcare. For psychiatrists this often includes managing raised prolactin levels in the context of medication. However, they must consider the wider differentials of a raised prolactin level and the possible impact of treatments. For that reason, in this review we start with an overview of prolactin physiology before considering hyperprolactinaemia both in the context of antipsychotic therapy and its wider differentials, including prolactinoma. Investigation and management are considered and key practice points developed.

Although halide perovskites (HaPs) are synthesized in ways that appear antithetical to those required for yielding high-quality semiconductors, the properties of the resulting materials imply, particularly for single crystals, ultralow densities of optoelectronically active defects. This article provides different views of this unusual behavior. We pose the question: Can present models of point defects in solids be used to interpret the experimental data and provide predictive power? The question arises because the measured ultralow densities refer to static defects using our present methods and models, while dynamic defect densities are ultrahigh, a result of the material being relatively soft, with a shallow electrostatic energy landscape, and with anharmonic lattice dynamics. All of these factors make the effects of dynamic defects on the materials’ optoelectronic properties minimal. We hope this article will stimulate discussions on the nontrivial question: Are HaPs, and especially the defects within them, business as usual?

OBJECTIVES/SPECIFIC AIMS: Screening the general population for prostate cancer with prostate specific antigen (PSA) continues to be controversial. Patients with advanced heart failure undergoing evaluation for suitability for cardiac transplantation are often requested to undergo prostate cancer screening, with guiding evidence generated from the general population. The objective of this study is to determine the clinical implications of a positive prostate cancer screen result in this patient population. METHODS/STUDY POPULATION: A retrospective cohort study was performed on all men that were referred to a tertiary care cardiac transplant center between January 2000 and December 2015. Patients were classified as having either a “positive screen” (PSA≥4 ng/mL) or a “negative screen” (PSA<4 ng/mL) at the point of evaluation. The primary outcome of time to listing for cardiac transplant (days) was calculated from the date of referral to the date of listing. A multivariable Cox proportional hazards model was developed to assess the association between a positive prostate cancer test result and listing for cardiac transplantation. RESULTS/ANTICIPATED RESULTS: Among the 704 patients included in this study, 66 men (9.4%) had a positive prostate cancer screen result. Men with a positive prostate cancer screen were approximately 4 year older (mean 58.5 vs. 54.1 years), more likely to have a diagnosis of Ischemic Cardiomyopathy (74% vs. 53%) and require continuous mechanical support (61% vs. 16%) at the point of transplant evaluation. The median time for listing for cardiac transplant was greater in patients with a positive PSA (119 vs. 48 days, p<0.05). After adjusting for age, renal function, clinical status at evaluation, history of COPD, and year of referral, patients with a positive prostate cancer screen had a reduced hazards ratio (HR) for progressing to cardiac transplant listing compared with those with a negative screen (HR 0.58, 95%CI: 0.38–0.91). DISCUSSION/SIGNIFICANCE OF IMPACT: Screening patients undergoing cardiac transplant evaluation for prostate cancer with PSA has a low diagnostic yield. An individual’s PSA value is influenced by their age and clinical status at the time of screening, with a positive screen being associated with a reduced likelihood for progressing to listing for cardiac transplant.

The grain boundary network of nanocrystalline Cu foils was modified by the application of cyclic loadings and elevated temperatures. Broadly, the changes to the boundary network were directly correlated with the applied temperature and accumulated strain, including a 300% increase in the twin length fraction. By independently varying each treatment variable, a matrix of grain boundary statistics was built to check the plausibility of hypothesized mechanisms against their expected temperature and stress/strain dependences. These comparisons allow the field of candidate mechanisms to be significantly narrowed. Most importantly, the effects of temperature and strain on twin length fraction were found to be strongly synergistic, with the combined effect being ∼150% that of the summed individual contributions. Looking beyond scalar metrics, an analysis of the grain boundary network showed that twin related domain formation favored larger sizes and repeated twin variant selection over the creation of many small domains with diverse variants.