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Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

This paper presents fluid dynamics simulation data associated with two test cases in the related research article [1]. In this article, an efficient bimaterial Riemann problem solver is proposed to accelerate multi-material flow simulations that involve complex thermodynamic equations of state and strong discontinuities across material interfaces. The first test case is a one-dimensional benchmark problem, featuring large density jump (4 orders of magnitude) and drastically different thermodynamics relations across a material interface. The second test case simulates the nucleation of a pear-shaped vapor bubble induced by long-pulsed laser in water. This multiphysics simulation combines laser radiation, phase transition (vaporization), non-spherical bubble expansion, and the emission of acoustic and shock waves. Both test cases are performed using the M2C solver, which solves the three-dimensional Eulerian Navier-Stokes equations, utilizing the accelerated bimaterial Riemann solver. Source codes provided in this paper include the M2C solver and a standalone version of the accelerated Riemann problem solver. These source codes serve as references for researchers seeking to implement the acceleration algorithms introduced in the related research article. Simulation data provided include fluid pressure, velocity, density, laser radiance and bubble dynamics. The input files and the workflow to perform the simulations are also provided. These files, together with the source codes, allow researchers to replicate the simulation results presented in the research article, which can be a starting point for new research in laser-induced cavitation, bubble dynamics, and multiphase flow in general.

Background & Aims: Pancreatic ductal adenocarcinoma can develop from precursor lesions, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN). Previous studies indicated that loss of Acvr1b accelerates the Kras-mediated development of papillary IPMN in the mouse pancreas; however, the cell type predominantly affected by these genetic changes remains unclear. Methods: We investigated the contribution of cellular origin by inducing IPMN associated mutations (KRASG12D expression and Acvr1b loss) specifically in acinar (Ptf1aCreER;KrasLSL-G12D;Acvr1bfl/fl mice) or ductal (Sox9CreER;KrasLSL-G12D;Acvr1bfl/fl mice) cells in mice. We then performed magnetic resonance imaging and a thorough histopathologic analysis of their pancreatic tissues. Results: The loss of Acvr1b increased the development of pancreatic intraepithelial neoplasia and IPMN-like lesions when either acinar or ductal cells expressed a Kras mutation. Magnetic resonance imaging, immunohistochemistry, and histology revealed large IPMN-like lesions in these mice that exhibited features of flat, gastric epithelium. In addition, cyst formation in both mouse models was accompanied by chronic pancreatitis. Experimental acute pancreatitis accelerated the development of large mucinous cysts and pancreatic intraepithelial neoplasia when acinar, but not ductal, cells expressed mutant Kras and lost Acvr1b. Conclusions: These findings indicate that loss of Acvr1b in the presence of the Kras oncogene promotes the development of large and small precancerous lesions from both ductal and acinar cells. However, the IPMN-like phenotype was not equivalent to that observed when these mutations were made in all pancreatic cells during development. Our study underscores the significance of the cellular context in the initiation and progression of precursor lesions from exocrine cells.

Holmium:yttrium–aluminum-garnet (Ho:YAG) laser lithotripsy (LL) has been the treatment of choice for kidney stone disease for more than two decades, yet the mechanisms of action are not completely clear. Besides photothermal ablation, recent evidence suggests that cavitation bubble collapse is pivotal in kidney stone dusting when the Ho:YAG laser operates at low pulse energy (Ep) and high frequency (F). In this work, we perform a comprehensive series of experiments and model-based simulations to dissect the complex physical processes in LL. Under clinically relevant dusting settings (Ep = 0.2 J, F = 20 Hz), our results suggest that majority of the irradiated laser energy (>90 %) is dissipated by heat generation in the fluid surrounding the fiber tip and the irradiated stone surface, while only about 1 % may be consumed for photothermal ablation, and less than 0.7 % is converted into the potential energy at the maximum bubble expansion. We reveal that photothermal ablation is confined locally to the laser irradiation spot, whereas cavitation erosion is most pronounced at a fiber tip-stone surface distance about 0.5 mm where multi foci ring-like damage outside the thermal ablation zone is observed. The cavitation erosion is caused by the progressively intensified collapse of jet-induced toroidal bubble near the stone surface (

Objective: The current total cavopulmonary connection Fontan has competing inflows and outflows, creating hemodynamic inefficiencies that contribute to Fontan failure and complicate placement and efficiency of mechanical circulatory support. We propose a novel convergent cavopulmonary connection (CCPC) Fontan design to create a single, converged venous outflow to the pulmonary arteries, thus increasing efficiency and mechanical circulatory support access. We then evaluate the feasibility and hemodynamic performance of the CCPC in various patient sizes using computational fluid dynamic assessments of computer-aided designs. Methods: Cardiac magnetic resonance imaging data from 12 patients with single ventricle (10 total cavopulmonary connection, 2 Glenn) physiology (body surface area, 0.5-2.0 m2) were segmented to create 3-dimensional replicas of all thoracic structures. Surgically feasible CCPC shapes within constraints of anatomy were created using iterative computational fluid dynamic and clinician input. Designs varied based on superior and inferior vena cava conduit sizes, coronal attachment height, coronal entry angle, and axial entry angle of the superior vena cava to the inferior vena cava. CCPC designs were optimized based on efficiency (indexed power loss), risk of arteriovenous malformations (hepatic flow distribution), and risk of flow stasis (% nonphysiologic wall shear stress). Results: All CCPC designs met hemodynamic performance thresholds for indexed power loss and hepatic flow distribution. CCPC designs showed improvements in reducing % nonphysiologic wall shear stress and balancing HFD. Conclusions: CCPC is physiologically and surgically feasible in various patient sizes using validated computational fluid dynamic models. CCPC configuration has analogous indexed power loss, hepatic flow distribution, and % nonphysiologic wall shear stress compared with total cavopulmonary connection, and the single inflow and outflow may ease mechanical circulatory support therapies. Further studies are required for design optimization and mechanical circulatory support institution.

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

The simulation data presented in this paper describes the formation and growth of an elongated bubble induced by a long-pulsed laser. The simulation is performed using the M2C solver, which is a recently developed three-dimensional finite volume Navier-Stokes CFD solver. The solver is used to simulate the fluid dynamics of the liquid water, the laser radiation, the laser-induced vaporization, and the fluid dynamics of the bubble after its formation. The data presented in this paper corresponds to a representative case of the cavitation induced by a narrow Gaussian beam (cf. [1]). Simulation data include laser radiance, fluid velocity, pressure, temperature, and bubble dynamics. The input files and the workflow to perform this simulation are also provided. With the information provided in this paper, researchers can repeat this simulation, and use it as a starting point to study related problems involving laser-induced cavitation, continuous vaporization, and bubble dynamics in general.

The simulation data presented in this paper describes the interaction between a thin-walled aluminum cylinder and a gas bubble in a near-field underwater explosion. The simulation is performed using the AERO-F/S solvers. The finite element AERO-S solver is used to simulate the structural dynamics of the cylinder, including its yielding and collapse. The AERO-F solver is used to simulate the fluid dynamics of the explosion bubble, the surrounding liquid water, and the air inside the cylinder. The two solvers are coupled using an embedded boundary method and the FInite Volume method with Exact two-material Riemann problems (FIVER). The data presented in this paper corresponds to a representative case with initial pressure p0=12.5MPa inside the bubble (cf. [1]). Simulation data include structural stress and deformation, fluid velocity, pressure and bubble dynamics. The input files and the workflow to perform this simulation are also provided. With the information provided in this paper, researchers can repeat this simulation, and use it as a starting point to study related problems involving cavitation bubbles, underwater explosion, and fluid-structure interaction in general.

Purpose: To describe a case of bilateral infectious scleritis secondary to Histoplasma capsulatum in the setting of a locally and systemically immunosuppressed patient. Observations: A 45-year-old man with HLA-B27 associated ankylosing spondylitis and anterior uveitis on systemic secokinumab, underwent bilateral cataract extraction which required extensive peri-operative steroids, including intravitreal triamcinolone, topical prednisolone, and oral prednisone. Six weeks after cataract surgery, the patient presented with mild eye irritation and was found to have bilateral subconjunctival purulence and necrosis. Histoplasma capsulatum was identified on fungal cultures and confirmed by DNA probe. The patient was treated with fortified amphotericin drops and oral itraconazole with complete resolution of scleritis. Conclusion and importance: H. capsulatum is a rare cause of infectious scleritis that must be considered in our immunosuppressed and post-surgical patients.

Summary: Given its role as the source of definitive hematopoietic cells, we sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here, we find that endothelium-specific transposon mutagenesis in mice promotes hematopoietic pathologies that are both myeloid and lymphoid in nature. Frequently mutated genes included previously recognized cancer drivers and additional candidates, such as Pi4ka, a lipid kinase whose mutation was found to promote myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism involving deregulation of AKT, MAPK, SRC, and JAK-STAT signaling. Finally, we provide evidence linking PI4KAP2, previously considered a pseudogene, to human myeloid and erythroid leukemia. : Using transposon mutagenesis that targets the endothelium, Ziyad et al. identify Pi4ka as an important regulator of hematopoiesis. Loss of Pi4ka inhibits myeloid and erythroid cell differentiation. Previously considered a pseudogene in humans, PI4KAP2 is shown to be protein-coding and a negative regulator of PI4KA signaling. Keywords: erythropoiesis, myelopoiesis, hematopoiesis, leukemia, hemogenic endothelium, lipid kinase, Pi4ka, PI4KAP2, Akt, Erk

Our data suggest that, after a myocardial infarction, integrin-associated protein CD47 on cardiac myocytes is elevated. In culture, increased CD47 on the surface of dying cardiomyocytes impairs phagocytic removal by immune cell macrophages. After myocardial ischemia and reperfusion, acute CD47 inhibition with blocking antibodies enhanced dead myocyte clearance by cardiac phagocytes and also improved the resolution of cardiac inflammation, reduced infarct size, and preserved cardiac contractile function. Early targeting of CD47 in the myocardium after reperfusion may be a new strategy to enhance wound repair in the ischemic heart.

Research into stalking victimization has proliferated over the last three decades, but little research has been done with Canadian data and several theoretical questions related to stalking victimization risk remain largely unanswered. To address the gaps in the literature, this study advances an integrated approach of neighborhood social support from criminology and comorbidity model from health science to examine the correlates of stalking victimization. Relying on data from Canadian General Social Survey, results confirm that the correlation model is better justifiable than the causal model in exploring the relationships between risk factors and being stalked and that variables broadly derived from social support theory, such as community order and trust, are statistically significant correlates of stalking victimization. In addition, most variables in the comorbidity model are significant correlates of stalking victimization. We conclude that social contexts and individual life habits are both important for the risk of stalking victimization., (© 2020 Published by Elsevier Ltd.)