This editorial considers the value and nature of academic psychiatry by asking what defines the specialty and psychiatrists as academics. We frame academic psychiatry as a way of thinking that benefits clinical services and discuss how to inspire the next generation of academics.

OBJECTIVES/GOALS: Single nucleotide polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with Type 2 Diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The metabolic function of TCF7L2 in the liver remains to be fully elucidated, but we hypothesized that TCF7L2 contributes to NAFLD through regulation of zonal metabolic pathways. METHODS/STUDY POPULATION: Using single nuclei RNA sequencing, we examined Tcf7l2 expression in periportal (PP) hepatocytes around the portal triad and pericentral (PC) hepatocytes surrounding the central vein of the liver. To visualize TCF7L2 transcriptional activity we used a TCF reporter mice, which expresses an H2B-eGFP fusion protein downstream of the conserved TCF DNA binding site. We disrupted Tcf7l2 transcriptional activity in mouse liver by breeding mice with a floxed Tcf7l2 exon 11, which encodes part of the DNA binding domain (DBD), to albumin-Cre mice (Hep-TCF7L2ΔDBD). Eight-week-old mice were fed a choline-deficient amino acid-defined high fat (CDAHFD) diet for 8 weeks. In liver samples harvested from these mice, we examined disruption to several key zonated metabolic pathways, and quantified the development of fibrosis. RESULTS/ANTICIPATED RESULTS: Single nuclei analysis revealed that Tcf7l2 mRNA was expressed primarily in parenchymal cells of the liver but was ubiquitous across the liver lobule. However, in immunofluorescence analysis of TCF reporter mice, the transcriptional activity of TCF7L2 was highly restricted to PC hepatocytes. Classic PC hepatocyte markers, including glutamine synthetase (Glul), were absent in Hep-TCF7L2ΔDBD mice. Following the CDAHFD, Hep-TCF7L2ΔDBD mice developed more severe fibrosis in histological analysis, and expressed elevated levels of genes involved in fibrogenesis, collagen synthesis and TGFβ signaling. Hep-TCF7L2ΔDBD mice also displayed hepatic cholesterol accumulation following the CDAHFD, which was likely the result of impaired pericentral bile acid synthesis. DISCUSSION/SIGNIFICANCE: Our results suggest that TCF7L2 plays an important role in the regulation of zonated metabolic pathways, which may contribute to the development of fibrosis. Ongoing analyses are exploring the mechanisms regulating the zonal transcriptional activity of TCF7L2.

OBJECTIVES/GOALS: Single nucleotide polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with Type 2 Diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). The metabolic function of TCF7L2 in the liver remains to be fully elucidated, but we hypothesized that TCF7L2 contributes to NAFLD through regulation of zonal metabolic pathways. METHODS/STUDY POPULATION: Using single nuclei RNA sequencing, we examined Tcf7l2 expression in periportal (PP) hepatocytes around the portal triad and pericentral (PC) hepatocytes surrounding the central vein of the liver. To visualize TCF7L2 transcriptional activity we used a TCF reporter mice, which expresses an H2B-eGFP fusion protein downstream of the conserved TCF DNA binding site. We disrupted Tcf7l2 transcriptional activity in mouse liver by breeding mice with a floxed Tcf7l2 exon 11, which encodes part of the DNA binding domain (DBD), to albumin-Cre mice (Hep-TCF7L2ΔDBD). Eight-week-old mice were fed a choline-deficient amino acid-defined high fat (CDAHFD) diet for 8 weeks. In liver samples harvested from these mice, we examined disruption to several key zonated metabolic pathways, and quantified the development of fibrosis. RESULTS/ANTICIPATED RESULTS: Single nuclei analysis revealed that Tcf7l2 mRNA was expressed primarily in parenchymal cells of the liver but was ubiquitous across the liver lobule. However, in immunofluorescence analysis of TCF reporter mice, the transcriptional activity of TCF7L2 was highly restricted to PC hepatocytes. Classic PC hepatocyte markers, including glutamine synthetase (Glul), were absent in Hep-TCF7L2ΔDBD mice. Following the CDAHFD, Hep-TCF7L2ΔDBD mice developed more severe fibrosis in histological analysis, and expressed elevated levels of genes involved in fibrogenesis, collagen synthesis and TGFβsignaling. Hep-TCF7L2ΔDBD mice also displayed hepatic cholesterol accumulation following the CDAHFD, which was likely the result of impaired pericentral bile acid synthesis. DISCUSSION/SIGNIFICANCE: Our results suggest that TCF7L2 plays an important role in the regulation of zonated metabolic pathways, which may contribute to the development of fibrosis. Ongoing analyses are exploring the mechanisms regulating the zonal transcriptional activity of TCF7L2.

Malposition of the branch pulmonary arteries (MBPA) is an unusual malformation characterised by anomalous origin of both pulmonary arteries from the main pulmonary trunk. To date, only few cases have been reported. Herein, we present the first case report of a 3-day-old, full-term male neonate with the lesser form of crossed pulmonary arteries in Saudi Arabia detected by echocardiography and confirmed by cardiac CT. Crossed pulmonary arteries is not a rare anomaly, but it is a somewhat underreported anomaly, and their recognition is important because it is usually associated with other CHDs, airway obstruction, extra-cardiac anomalies, and certain genetic syndromes.

Globally, countries have used diverse methods to report data during the COVID-19 pandemic. Using international guidelines and principles of emergency management, we compare national data reporting systems in African countries in order to determine lessons for future pandemics. We analyse COVID-19 reporting practices across 54 African countries through 2020. Reporting systems were diverse and included summaries, press releases, situation reports and online dashboards. These systems were communicated via social media accounts and websites belonging to ministries of health and public health. Data variables from the reports included event detection (cases/deaths/recoveries), risk assessment (demographics/co-morbidities) and response (total tests/hospitalisations). Of countries with reporting systems, 36/53 (67.9%) had recurrent situation reports and/or online dashboards which provided more extensive data. All of these systems reported cases, deaths and recoveries. However, few systems contained risk assessment and response data, with only 5/36 (13.9%) reporting patient co-morbidities and 9/36 (25%) including total hospitalisations. Further evaluation of reporting practices in Cameroon, Egypt, Kenya, Senegal and South Africa as examples from different sub-regions revealed differences in reporting healthcare capacity and preparedness data. Improving the standardisation and accessibility of national data reporting systems could augment research and decision-making, as well as increase public awareness and transparency for national governments.

Streamwise velocity and wall-shear stress are acquired simultaneously with a hot-wire and an array of azimuthal/spanwise-spaced skin friction sensors in large-scale pipe and boundary layer flow facilities at high Reynolds numbers. These allow for a correlation analysis on a per-scale basis between the velocity and reference skin friction signals to reveal which velocity-based turbulent motions are stochastically coherent with turbulent skin friction. In the logarithmic region, the wall-attached structures in both the pipe and boundary layers show evidence of self-similarity, and the range of scales over which the self-similarity is observed decreases with an increasing azimuthal/spanwise offset between the velocity and the reference skin friction signals. The present empirical observations support the existence of a self-similar range of wall-attached turbulence, which in turn are used to extend the model of Baars et al. (J. Fluid Mech., vol. 823, p. R2) to include the azimuthal/spanwise trends. Furthermore, the region where the self-similarity is observed correspond with the wall height where the mean momentum equation formally admits a self-similar invariant form, and simultaneously where the mean and variance profiles of the streamwise velocity exhibit logarithmic dependence. The experimental observations suggest that the self-similar wall-attached structures follow an aspect ratio of $7:1:1$ in the streamwise, spanwise and wall-normal directions, respectively.

This study presents findings from a first-of-its-kind measurement campaign that includes simultaneous measurements of the full velocity and vorticity vectors in both pipe and boundary layer flows under matched spatial resolution and Reynolds number conditions. Comparison of canonical turbulent flows offers insight into the role(s) played by features that are unique to one or the other. Pipe and zero pressure gradient boundary layer flows are often compared with the goal of elucidating the roles of geometry and a free boundary condition on turbulent wall flows. Prior experimental efforts towards this end have focused primarily on the streamwise component of velocity, while direct numerical simulations are at relatively low Reynolds numbers. In contrast, this study presents experimental measurements of all three components of both velocity and vorticity for friction Reynolds numbers $Re_{\unicode[STIX]{x1D70F}}$ ranging from 5000 to 10 000. Differences in the two transverse Reynolds normal stresses are shown to exist throughout the log layer and wake layer at Reynolds numbers that exceed those of existing numerical data sets. The turbulence enstrophy profiles are also shown to exhibit differences spanning from the outer edge of the log layer to the outer flow boundary. Skewness and kurtosis profiles of the velocity and vorticity components imply the existence of a ‘quiescent core’ in pipe flow, as described by Kwon et al. (J. Fluid Mech., vol. 751, 2014, pp. 228–254) for channel flow at lower $Re_{\unicode[STIX]{x1D70F}}$, and characterize the extent of its influence in the pipe. Observed differences between statistical profiles of velocity and vorticity are then discussed in the context of a structural difference between free-stream intermittency in the boundary layer and ‘quiescent core’ intermittency in the pipe that is detectable to wall distances as small as 5 % of the layer thickness.

Fully resolved measurements of turbulent boundary layers are reported for the Reynolds number range $Re_{\unicode[STIX]{x1D70F}}=6000{-}20\,000$. Despite several decades of research in wall-bounded turbulence there is still controversy over the behaviour of streamwise turbulence intensities near the wall, especially at high Reynolds numbers. Much of it stems from the uncertainty in measurement due to finite spatial resolution. Conventional hot-wire anemometry is limited for high Reynolds number measurements due to limited spatial resolution issues that cause attenuation in the streamwise turbulence intensity profile near the wall. To address this issue we use the nano-scale thermal anemometry probe (NSTAP), developed at Princeton University to conduct velocity measurements in the high Reynolds number boundary layer facility at the University of Melbourne. The NSTAP has a sensing length almost one order of magnitude smaller than conventional hot-wires. This enables us to acquire fully resolved velocity measurements of turbulent boundary layers up to $Re_{\unicode[STIX]{x1D70F}}=20\,000$. Results show that in the near-wall region, the viscous-scaled streamwise turbulence intensity grows with $Re_{\unicode[STIX]{x1D70F}}$ in the Reynolds number range of the experiments. A second outer peak in the streamwise turbulence intensity is also shown to emerge at the highest Reynolds numbers. Moreover, the energy spectra in the near-wall region show excellent inner scaling over the small to moderate wavelength range, followed by a large-scale influence that increases with Reynolds number. Outer scaling in the outer region is found to collapse the energy spectra over high wavelengths across various Reynolds numbers.

The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host–parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae, e.g. Syphacia minuta), show elements of temporal-site stability, with a rank order of measures among sites remaining similar over successive surveys. Hence, there are some elements of predictability in these systems.

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.

In order to potentially realize the advantages of planar parallel manipulators to be used for hybrid machine tools, the inherently abundant singularities which diminish the usable workspace must be eliminated. Proper structure synthesis and dimensional synthesis can provide a good solution. So, a non-conventional architecture of a three-PPR planar parallel manipulator is proposed in this paper for a hybrid machine tool. The proposed architecture permits a large dexterous workspace with unlimited orientation capability and no singularities. It also provides partially decoupled motion which permits independent actuators control. The kinematic, singularity, orientation capability and workspace analyses of the proposed manipulator are studied to verify those advantages. Based on a non-dimensional design parameter space, the highly important indices for this application namely the workspace index (WI), the motion/force transmission index, the kinematic and dynamic dexterity indices and the stiffness index are selected to be maximized yielding proper dimensions of the design parameters. Those performance indices are proven to be uniform over all the workspace achieving highly important characteristics of uniform accuracy, acceleration characteristics, rigidity and force transmissibility. Performance evaluation is finally presented to verify the high performance of the proposed non-singular planar parallel manipulator with high orientation capability.