Increasing interest in three-dimensional nanostructures adds impetus to electron microscopy techniques capable of imaging at or below the nanoscale in three dimensions. We present a reconstruction algorithm that takes as input a focal series of four-dimensional scanning transmission electron microscopy (4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, and yttrium-stabilized zirconia, Y$_{0.095}$Zr$_{0.905}$O$_2$, heterostructure from data acquired with the specimen in a single plan-view orientation, with the epitaxial layers stacked along the beam direction. We demonstrate that Pb–Ir atomic columns are visible in the uppermost layers of the reconstructed volume. We compare this approach to the alternative techniques of depth sectioning using differential phase contrast scanning transmission electron microscopy (DPC-STEM) and multislice ptychographic reconstruction.

Several recent studies devote themselves to Mary Astell's feminist theory of virtue—her ‘serious proposal to the ladies’ to help women obtain wisdom, equality, and happiness, despite the prejudices of seventeenth-century custom. But there has been little scholarship on Astell's conception of heroic virtues, those exceptional character traits that raise their bearers above the ordinary course of nature. Astell's appropriation of heroic virtue poses a number of philosophical difficulties for her feminist ethics—heroic virtues are characteristically masculine, exceptional, and individualistic, ill-suited to a community-oriented feminism aimed at ordinary women. In this paper, we seek to investigate—and then dispel—these key difficulties. Our intention is to generate a new understanding of Astell's theory of virtue as a unique and sophisticated theory that equalizes and naturalizes heroic virtue for women.

Social isolation and loneliness in long-term care settings are a growing concern. Drawing on concepts of social citizenship, we developed a peer mentoring program in which resident mentors and volunteers formed a team, met weekly for training, and paired up to visit isolated residents. In this article, we explore the experiences of the resident mentors. As part of a larger mixed-methods study conducted in 10 sites in Canada, we interviewed mentors (n = 48) and analysed data using inductive thematic analysis. We identified three inter-related themes: Helping others, helping ourselves described the personal benefits experienced through adopting a helping role; Building a bigger social world encapsulated new connections with those visited, and; Facing challenges, learning together described how mentors dealt with challenges as a team. Our findings suggest that a structured approach to mentoring benefits residents and helps them feel confident taking on a role supporting their isolated peers.

A method for three-dimensional reconstruction of objects from defocused images collected at multiple illumination directions in high-resolution transmission electron microscopy is presented. The method effectively corrects for the Ewald sphere curvature by taking into account the in-particle propagation of the electron beam. Numerical simulations demonstrate that the proposed method is capable of accurately reconstructing biological molecules or nanoparticles from high-resolution defocused images under conditions achievable in single-particle electron cryo-microscopy or electron tomography with realistic radiation doses, non-trivial aberrations, multiple scattering, and other experimentally relevant factors. The physics of the method is based on the well-known Diffraction Tomography formalism, but with the phase-retrieval step modified to include a conjugation of the phase (i.e., multiplication of the phase by a negative constant). At each illumination direction, numerically backpropagating the beam with the conjugated phase produces maximum contrast at the location of individual atoms in the molecule or nanoparticle. The resultant algorithm, Conjugated Holographic Reconstruction, can potentially be incorporated into established software tools for single-particle analysis, such as, for example, RELION or FREALIGN, in place of the conventional contrast transfer function correction procedure, in order to account for the Ewald sphere curvature and improve the spatial resolution of the three-dimensional reconstruction.

This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.

PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.

After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.

Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.

OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.

Aphidophagous hoverflies (Diptera, Syrphidae, Syrphinae) are common flower visitors and aphid predators in a range of flowering plants, including fruit crops. Here, we investigate whether aphid prey DNA can be detected in the gut contents of hoverfly larvae from a commercial strawberry field as a proof of concept that a molecular approach can be used to measure agricultural biocontrol. We used high-throughput sequencing (HTS) to target insect DNA and compared the resulting data to reference databases containing aphid and hoverfly DNA sequences. We explored what impact incorporating wildflowers within polythene-clad tunnels may have on aphid DNA detection rates in hoverfly larvae. In a randomized block experiment, coriander (Coriandrum sativum), field forget-me-not (Myosotis arvensis) and corn mint (Mentha arvensis) plants were inserted in rows of strawberries. Their effect on aphid DNA detection rates was assessed. Aphid DNA was found in 55 of 149 specimens (37%) validating the method in principle for measuring agricultural services provided by hoverflies. Interestingly, detection rates were higher near plots with forget-me-not than plots with coriander, though detection rates in control plots did not differ significantly from either wildflower species. These findings confirm that hoverflies predate aphids in UK strawberry fields, and that HTS is a viable method of identifying aphid DNA in predatory hoverflies. We comment on the need for further method development to narrow down identifications of both predator and prey. We furthermore provide some evidence that there is an effect of intercropping strawberry crops with wildflowers which may affect aphid consumption in hoverfly larvae.

Children with CHD are at risk for psychosocial and neurodevelopmental difficulties, as well as lapses in care during their transition from paediatric to adult CHD providers. The American Heart Association and American Academy of Pediatrics released guidelines for best practices in the neurodevelopmental and transitional care for children with CHD in 2012 and 2011, respectively. CHD providers from 48 (42.1% response rate) geographically diverse cardiac clinics completed a 31-item electronic survey designed to assess the cardiac teams’ consistency with neurodevelopmental evaluation and management recommendations, consultation/liaison patterns for psychosocial services, and procedures regarding transitional services for emerging adults. Responses suggest most cardiac teams refer patients to psychosocial services as needed, and 39.6% of teams screen for psychosocial distress. CHD providers at 66.7% of cardiac clinics reported a formal neurodevelopmental programme/clinic. Nearly half of cardiac teams conduct routine neurodevelopmental evaluations, most frequently occurring at 9 months of age. Less than 10% of cardiac clinics have resources to meet the American Heart Association and American Academy of Pediatrics 2012 neurodevelopmental evaluation and management guidelines. Formal paediatric to adult CHD transition programmes were reported at 70.8% of cardiac clinics and were associated with younger ages of transition to adult CHD care. Care practices varied across the 48 represented cardiac clinics, indicating inconsistent practices for patients with CHD. Barriers and facilitators to the provision of care for children in these areas were reported and are presented. More support is needed for cardiac clinics to continue improvements in psychosocial, neurodevelopmental, and transitional care services.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

The transition from the Late Archaic to the Late Early Formative period witnessed profound changes in the Maya lowlands. In addition to the establishment of the first settlements and agrarian communities, this critical phase of cultural development heralded the introduction of ceramics, saw changes in lithic technology, gave rise to inter-regional trade and exchange, and witnessed the introduction of a complex symbolic system expressed on portable objects. In this article, we synthesize data collected over the past several decades by various archaeological projects in western Belize to provide an overview of the cultural changes that unfolded during the Late Archaic to Late Early Formative period in the Upper Belize River Valley. We also provide evidence indicating that it was during this critical transitional period that we begin to see the establishment of several cultural traditions that became uniquely lowland Maya.