Congenital anomalies of the iliac arterial system are rare and can be associated with ischemia. With an increase in vascular imaging and interventions, such anomalies are likely to be encountered with greater frequency. We present the case of a 25-year-old female who was incidentally found to have absence of the common iliac arteries bilaterally and the left internal iliac artery, a constellation not previously reported in the literature. We present relevant imaging findings, review embryonic vascular development, and discuss potential clinical implications.

Upscaling groundwater flow is a fundamental challenge in hydrogeology. This study proposed time-fractional flow equations (t-FFEs) for upscaling long-term, transient groundwater flow and propagation of pressure heads in heterogeneous media. Monte Carlo simulations showed that, with increasing variance and correlation of the hydraulic conductivity (K), flow dynamics gradually deviated from Darcian flow and exhibit sub-diffusive, time-dependent evolution which can be separated into three major stages. At the early stage, the interconnected high-K zones dominated flow, while at intermediate times, the transverse flow due to mixed high- and low-K zones caused delayed rise of the piezometric head. At late times when flow in the relatively high-K domains reached stability, cells with very low-K continued to block the entry of water and generate “islands” with low piezometric head, significantly extending the temporal evolution of the piezometric head. The elongated water breakthrough curve cannot be quantified by the flow equation with an effective K, the space-fractional flow equation, or the multi-rate mass transfer (MRMT) flow model with a few rates, motivating the development of t-FFEs assuming temporally non-Darcian flow. Model applications showed that both the early and intermediate stages of flow dynamics can be captured by a single-index t-FFE (whose index is the exponent of the power-law probability density function of the random operational time for water parcels), but the overall evolution of flow dynamics, especially the enhanced retention of flow at later times, required a distributed-order t-FFE with variable indexes for different flow phases that can dominate flow dynamics at different stages. Therefore, transient groundwater flow in aquifers with spatially stationary heterogeneity can be temporally non-Darcian and non-stationary, due to the time-sensitive, combined effects of interconnected high-K channels and isolated low-K deposits on flow dynamics (which is the hydrogeological mechanism for the temporally non-Darcian flow and sub-diffusive pressure propagation), whose long-term behavior can be quantified by multi-index stochastic models.

Performance errors drive motor learning for many tasks. Some researchers have suggested that reducing performance errors with haptic guidance can benefit learning by demonstrating correct movements, while others have suggested that artificially increasing errors will force faster and more complete learning. This study compared the effect of these two techniques--haptic guidance and error amplification--as healthy subjects learned to play a computerized pinball-like game. The game required learning to press a button using wrist movement at the correct time to make a flipper hit a falling ball to a randomly positioned target. Errors were decreased or increased using a robotic device that retarded or accelerated wrist movement, based on sensed movement initiation timing errors. After training with either error amplification or haptic guidance, subjects significantly reduced their timing errors and generalized learning to untrained targets. However, for a subset of more skilled subjects, training with amplified errors produced significantly greater learning than training with the reduced errors associated with haptic guidance, while for a subset of less skilled subjects, training with haptic guidance seemed to benefit learning more. These results suggest that both techniques help enhanced performance of a timing task, but learning is optimized if training subjects with the appropriate technique based on their baseline skill level.

Unlabelled

Awareness of cancer therapy-induced toxicities is important for all clinicians treating patients with cancer. Cancer therapy has evolved to include classic cytotoxic agents in addition to newer options such as targeted agents and catheter-directed chemoembolisation. Several adverse affects can result from the wide array of treatments including effects on the liver, pancreas, and biliary system that can be visualised on imaging. These complications include sinusoidal obstruction syndrome, fatty liver, pseudocirrhosis, acute hepatitis, pancreatitis, pancreatic atrophy, cholecystitis, biliary sclerosis, and biliary stasis. Many of these toxicities are manageable and reversible with supportive therapies and/or cessation of cancer therapy. The objective of this review is to discuss the imaging findings associated with cancer therapy-induced toxicity of the liver, biliary system, and pancreas.

Teaching points

• Cancer therapy can have adverse effects on the hepatobiliary system and pancreas. • Cancer therapy-induced toxicities can be visualised on imaging. • Knowledge of imaging changes associated with cancer therapy complications can improve treatment.

Purpose

Use of magnetic resonance imaging (MRI)/transrectal ultrasound fusion biopsies to determine the accuracy of multiparametric MRI (mpMRI), using Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2), for detecting clinically significant prostate cancer in the overall gland and specifically the peripheral zone (PZ) and transitional zone (TZ).

Methods

A retrospective analysis of patients who underwent fusion biopsy identified 137 men with 231 prostate lesions was approved by the Institutional Review Board. Subjects initially classified under PI-RADSv1 criteria were regraded using PI-RADSv2 by a radiologist blinded to PI-RADSv1 score and biopsy results. Spearman correlation, chi-squared, and logistic regression analysis were performed.

Results

There was positive correlation between PI-RADSv2 and Gleason scores (P < 0.001). In the PZ, mpMRI demonstrated 100% sensitivity, 100% negative predictive value, and 35.9% positive predictive value, compared to 100%, 100%, and 27.1%, respectively, for TZ lesions. When predicting clinically significant prostate cancer, the PI-RADSv2 area under the curve for TZ lesions was 0.844 (95% CI: 0.753-0.935, P < 0.001) and 0.769 (95% CI: 0.684-0.854, P < 0.001) for PZ lesions. Combining PI-RADSv2 with additional risk factors (body mass index, prostate-specific antigen density, digital rectal examination) improved the area under curve.

Conclusions

PI-RADSv2 achieves excellent sensitivity and negative predictive value for both PZ and TZ lesions.

Membrane contact sites (MCS), close membrane apposition between organelles, are platforms for interorganellar transfer of lipids including cholesterol, regulation of lipid homeostasis, and co-ordination of endocytic trafficking. Sphingosine kinases (SphKs), two isoenzymes that phosphorylate sphingosine to the bioactive sphingosine-1-phosphate (S1P), have been implicated in endocytic trafficking. However, the physiological functions of SphKs in regulation of membrane dynamics, lipid trafficking and MCS are not known. Here, we report that deletion of SphKs decreased S1P with concomitant increases in its precursors sphingosine and ceramide, and markedly reduced endoplasmic reticulum (ER) contacts with late endocytic organelles. Expression of enzymatically active SphK1, but not catalytically inactive, rescued the deficit of these MCS. Although free cholesterol accumulated in late endocytic organelles in SphK null cells, surprisingly however, cholesterol transport to the ER was not reduced. Importantly, deletion of SphKs promoted recruitment of the ER-resident cholesterol transfer protein Aster-B (also called GRAMD1B) to the plasma membrane (PM), consistent with higher accessible cholesterol and ceramide at the PM, to facilitate cholesterol transfer from the PM to the ER. In addition, ceramide enhanced in vitro binding of the Aster-B GRAM domain to phosphatidylserine and cholesterol liposomes. Our study revealed a previously unknown role for SphKs and sphingolipid metabolites in governing diverse MCS between the ER network and late endocytic organelles versus the PM to control the movement of cholesterol between distinct cell membranes.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY_207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF_9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK_361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.