Clinical and Deep-Learned Evaluation of MR-Guided Self-Supervised PET Reconstruction.

Reduced dose Positron Emission Tomography (PET) lowers the radiation dose to patients and reduces costs. Lower count data, however, degrades reconstructed image quality. Advanced reconstruction methods help mitigate image quality losses, but it is important to assess the resulting images from a clinical perspective.

Deep Learning for Breast Cancer Risk Prediction: Application to a Large Representative UK Screening Cohort.

Purpose To develop an artificial intelligence (AI) deep learning tool capable of predicting future breast cancer risk from a current negative screening mammographic examination and to evaluate the model on data from the UK National Health Service Breast Screening Program. Materials and Methods The OPTIMAM Mammography Imaging Database contains screening data, including mammograms and information on interval cancers, for more than 300 000 female patients who attended screening at three different sites in the United Kingdom from 2012 onward. Cancer-free screening examinations from women aged 50-70 years were performed and classified as risk-positive or risk-negative based on the occurrence of cancer within 3 years of the original examination.

Non-rigid motion-compensated 3D whole-heart T mapping in a hybrid 3T PET-MR system.

Purpose: Simultaneous PET-MRI improves inflammatory cardiac disease diagnosis. However, challenges persist in respiratory motion and mis-registration between free-breathing 3D PET and 2D breath-held MR images. We propose a free-breathing non-rigid motion-compensated 3D T -mapping sequence enabling whole-heart myocardial tissue characterization in a hybrid 3T PET-MR system and provides non-rigid respiratory motion fields to correct also simultaneously acquired PET data.

JNTX-101, a novel albumin-encapsulated gemcitabine prodrug, is efficacious and operates via caveolin-1-mediated endocytosis.

Albumin is an attractive candidate carrier for the development of novel therapeutic drugs. Gemcitabine has been FDA approved for the treatment of solid tumors; however, new drugs that optimize gemcitabine delivery are not available for clinical use. The aim of this study was to test the efficacy of a novel albumin-encapsulated gemcitabine prodrug, JNTX-101, and investigate whether Cav-1 expression predicts the therapeutic efficacy of JNTX-101.

Enantioselective Total Synthesis of (-)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones.

Herein, we describe the convergent enantioselective total synthesis of himalensine A in 18 steps, enabled by a highly enantio- and diastereoselective construction of the morphan core via a palladium/hydroxy proline co-catalyzed desymmetrization of vinyl-bromide-tethered cyclohexanones. The reaction pathway was illuminated by density functional theory calculations, which support an intramolecular Heck reaction of an -generated enamine intermediate, where exquisite enantioselectivity arises from intramolecular carboxylate coordination to the vinyl palladium species in the rate- and enantio-determining carbopalladation steps. The reaction tolerates diverse -derivatives, all-carbon quaternary centers, and trisubstituted olefins, providing access to molecular scaffolds found in a range of complex natural products.

Synoptic CT scan reporting of pancreatic adenocarcinoma to align with international consensus guidelines on surgical resectability: a Victorian pilot.

Background: Non-metastatic pancreatic ductal adenocarcinoma (PDAC) is classified as resectable (R), borderline resectable (BR) or locally advanced (LA). International Consensus Guidelines on these definitions exist, but have not been integrated into everyday Australian practice. The anatomical features on CT imaging lend themselves to synoptic reporting which should enhance completeness, comparability and consistency.

MR-guided motion-corrected PET image reconstruction for cardiac PET-MR.

Simultaneous PET-MR imaging has shown potential for the comprehensive assessment of myocardial health from a single examination. Furthermore, MR-derived respiratory motion information has been shown to improve PET image quality by incorporating this information into the PET image reconstruction. Separately, MR-based anatomically guided PET image reconstruction has been shown to perform effective denoising, but this has been so far demonstrated mainly in brain imaging.

Effects of acetate on cerebral blood flow, systemic inflammation, and behavior in alcohol use disorder.

Background: Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD.

The decline of butterflies in Europe: Problems, significance, and possible solutions.

We review changes in the status of butterflies in Europe, focusing on long-running population data available for the United Kingdom, the Netherlands, and Belgium, based on standardized monitoring transects. In the United Kingdom, 8% of resident species have become extinct, and since 1976 overall numbers declined by around 50%. In the Netherlands, 20% of species have become extinct, and since 1990 overall numbers in the country declined by 50%.

Bootstrap-Optimised Regularised Image Reconstruction for Emission Tomography.

In emission tomography, iterative image reconstruction from noisy measured data usually results in noisy images, and so regularisation is often used to compensate for noise. However, in practice, an appropriate, automatic and precise specification of the strength of regularisation for image reconstruction from a given noisy measured dataset remains unresolved. Existing approaches are either empirical approximations with no guarantee of generalisation, or else are computationally intensive cross-validation methods requiring full reconstructions for a limited set of preselected regularisation strengths.

Intercomparison of MR-informed PET image reconstruction methods.

Purpose: Numerous image reconstruction methodologies for positron emission tomography (PET) have been developed that incorporate magnetic resonance (MR) imaging structural information, producing reconstructed images with improved suppression of noise and reduced partial volume effects. However, the influence of MR structural information also increases the possibility of suppression or bias of structures present only in the PET data (PET-unique regions). To address this, further developments for MR-informed methods have been proposed, for example, through inclusion of the current reconstructed PET image, alongside the MR image, in the iterative reconstruction process.

Spatially-Compact MR-Guided Kernel EM for PET Image Reconstruction.

Positron emission tomography (PET) is a highly sensitive functional and molecular imaging modality which can measure picomolar concentrations of an injected radionuclide. However, the physical sensitivity of PET is limited, and reducing the injected dose leads to low count data and noisy reconstructed images. A highly effective way of reducing noise is to reparameterise the reconstruction in terms of MR-derived spatial basis functions.

Enantioselective Silver-Catalyzed Cascade Synthesis of Fused Lactone and Lactam Oxazolines.

A new and highly stereoselective cascade reaction between isocyanoacetate esters and α-hydroxy and α-amino ketones has been developed. A cinchona alkaloid derived aminophosphine/silver(I) catalyst complex promoted the reaction and enabled the ready synthesis of fused bicyclic γ-lactone and γ-lactam oxazolines with high enantiocontrol (up to 99% ee).

Multi-Tracer Guided PET Image Reconstruction.

Multi-tracer positron emission tomography (PET) has the potential to enhance PET imaging by providing complementary information from different physiological processes. However, one or more of the images may present high levels of noise. Guided image reconstruction methods transfer information from a guide image into the PET image reconstruction to encourage edge-preserving noise reduction.

MR-Guided Kernel EM Reconstruction for Reduced Dose PET Imaging.

PET image reconstruction is highly susceptible to the impact of Poisson noise, and if shorter acquisition times or reduced injected doses are used, the noisy PET data become even more limiting. The recent development of kernel expectation maximisation (KEM) is a simple way to reduce noise in PET images, and we show in this work that impressive dose reduction can be achieved when the kernel method is used with MR-derived kernels. The kernel method is shown to surpass maximum likelihood expectation maximisation (MLEM) for the reconstruction of low-count datasets (corresponding to those obtained at reduced injected doses) producing visibly clearer reconstructions for unsmoothed and smoothed images, at all count levels.

Penalized maximum likelihood simultaneous longitudinal PET image reconstruction with difference-image priors.

Purpose: Many clinical contexts require the acquisition of multiple positron emission tomography (PET) scans of a single subject, for example, to observe and quantitate changes in functional behaviour in tumors after treatment in oncology. Typically, the datasets from each of these scans are reconstructed individually, without exploiting the similarities between them. We have recently shown that sharing information between longitudinal PET datasets by penalizing voxel-wise differences during image reconstruction can improve reconstructed images by reducing background noise and increasing the contrast-to-noise ratio of high-activity lesions.

Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes.

Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes (T1D), the DQ8 molecule is common, confers significant disease risk, and is involved in disease pathogenesis. We hypothesized that blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells.

Simultaneous maximum a posteriori longitudinal PET image reconstruction.

Positron emission tomography (PET) is frequently used to monitor functional changes that occur over extended time scales, for example in longitudinal oncology PET protocols that include routine clinical follow-up scans to assess the efficacy of a course of treatment. In these contexts PET datasets are currently reconstructed into images using single-dataset reconstruction methods. Inspired by recently proposed joint PET-MR reconstruction methods, we propose to reconstruct longitudinal datasets simultaneously by using a joint penalty term in order to exploit the high degree of similarity between longitudinal images.

Access to a Guanacastepene and Cortistatin-Related Skeleton via Ethynyl Lactone Ireland-Claisen Rearrangement and Transannular (4 + 3)-Cycloaddition of an Azatrimethylenemethane Diyl.

Heating a 2,5-furanocyclic (2-azidoethyl)allene initiates a cascade reaction comprising azide-allene cycloaddition, loss of nitrogen, and azatrimethylenemethane (ATMM) diyl-furan transannular (4 + 3)-cycloaddition. The major product of this reaction contains the pentacyclic core common to guanacastepenes D and H and radianspenes J-L; in addition, the central oxa-bridged cycloheptene ring, flanked by two carbocyclic rings, is structurally related to the ABC-ring system found in the cortistatins. This is the first reported synthetic application of a "free" (nonconjugated) ATMM.

Decline of a Rare Moth at Its Last Known English Site: Causes and Lessons for Conservation.

The conditions required by rare species are often only approximately known. Monitoring such species over time can help refine management of their protected areas. We report population trends of a rare moth, the Dark Bordered Beauty Epione vespertaria (Linnaeus, 1767) (Lepidoptera: Geometridae) at its last known English site on a protected lowland heath, and those of its host-plant, Salix repens (L.

Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes.

Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12-21 years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.

Profiling of membrane protein variants in a baculovirus system by coupling cell-surface detection with small-scale parallel expression.

Production of structure-grade mammalian membrane proteins in substantial quantities has been hindered by a lack of methods for effectively profiling multiple constructs expression in higher eukaryotic systems such as insect or mammalian cells. To address this problem, a specialized small-scale eukaryotic expression platform by Thomson Instrument Company (Vertiga-IM) was developed and used in tandem with a Guava EasyCyte microcapillary 96-well cytometer to monitor cell density and health and evaluate membrane protein expression. Two proof of concept experiments were conducted using the human beta(2)-adrenergic receptor (beta(2)AR) and the gap junction protein connexin26 (Cx26) in a baculovirus expression system.

A strategy to develop advanced pharmacy practice experiences.

Objective: To establish statewide medication, disease management, and other clinical programs to serve as advanced pharmacy practice experience (APPE) training sites for the University of Colorado at Denver and Health Sciences Center School of Pharmacy, and to guarantee year-round support for the programs by providing pharmacy students with the necessary competencies to carry a significant proportion of each program's workload.

Methods: Partnerships with pharmacies willing to use students to expand their scope of clinical practice or support existing programs were established. Partners were asked to choose the clinical program(s) they wished implemented or supported and were guaranteed that APPE students would contribute to carrying each program's clinical service workload for 48 week/year under the supervision of the partners' pharmacists.

An introductory pharmacy practice experience emphasizing student-administered vaccinations.

Objective: To introduce a requirement for second-professional year (P2) and third-professional year (P3) students to administer vaccinations to adults in community pharmacy-based immunization clinics.

Design: Second-professional year students were trained to administer influenza, pneumococcal, and other vaccinations to adults following the American Pharmacists Association's standards. All P2 students in fall 2004 and all P2 and P3 students in fall 2005 were assigned to 2 community pharmacy-based immunization clinics in the metropolitan Denver area under the supervision of immunization-certified staff pharmacists.

Antihypertensive Drug Utilization in Hypertensive Veterans With Complex Medication Profiles.

A pharmacy prescription database was used to identify patients at high risk for drug-related problems. Of the 1054 patients in the study, 687 had a diagnosis of hypertension. The utilization of antihypertensive medications was captured at three periods over 24 months (12 months before enrollment, at enrollment, and 12 months after enrollment).