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Multi-societal expert consensus statement on the safe administration of ultrasound contrast agents
(2025-02-21) Strom, Jordan B.; Appis, Andrew; Barr, Richard G.; Chammas, Maria C.; Clevert, Dirk-André; Darge, Kassa; Feinstein, Linda; Feinstein, Steven B.; Fowlkes, J. B.; Gorman, Beverly; Huang, Pintong; Kono, Yuko; Lopez-Mattei, Juan; Lyshchik, Andrej; Main, Michael L.; Matthias, Wilson; Merrill, Christina; Mulvagh, Sharon L.; Nihoyannopoulos, Petros; Olson, Joan; Piscaglia, Fabio; Porter, Thomas; Rabischoffsky, Arnaldo; Senior, Roxy; Stout, Jessica L.; Stanczak, Maria; Wilson, Stephanie R.
Abstract Contrast enhanced ultrasound (CEUS) offers a safe, reliable imaging option to establish a clinical diagnosis across a variety of multidisciplinary settings. This Expert Consensus Statement serves to outline expert opinion on what constitutes appropriate supervision and the essential components of safe CEUS practice. The purpose of this document is to empower institutions to allow sonographers, along with other trained medical professionals, to administer UCAs at the point of care, consistent with the updated scope of practice documentation and within the broad parameters of an individual’s training and licensure, while subject to appropriate supervision and meeting or exceeding minimum safety standards. This guidance was developed by the International Contrast Ultrasound Society and endorsed by the following organizations that represent ultrasound professionals: the British Society of Echocardiography, the Canadian Society of Echocardiography, the Society of Diagnostic Medical Sonography, the Society for Pediatric Radiology, the World Federation of Ultrasound in Medicine and Biology, the Brazilian College of Radiology, the Joint Review Committee for Diagnostic Medical Sonography, the Chinese Ultrasound Doctors Association, and the American Society of Neuroimaging. Additionally, this guidance document was affirmed or supported by the American Society of Echocardiography, the Association for Medical Ultrasound, and the Society for Vascular Ultrasound.
Integrated access to cancer screening: expanding access for cervical and colorectal cancer screening in rural and remote Northern Alberta, Canada using a mobile service to bring cancer screening closer to home
(2025-02-17) Wiseman, Jessica; Patterson, Kara; Kliewer, Gordon; Mueller, Mary; Mutti-Packer, Seema; Newsome, James; Lockerbie, Stacy; Hauber, Joan; Schwann, Monica; Yang, Huiming
Abstract Background The goal of the Integrated Access to Cancer Screening (IACS) initiative was to help reduce the disparity in cancer screening participation across Alberta by implementing an integrated mobile service delivery model for breast, cervical, and colorectal cancer screening in rural and remote communities in Northern Alberta, performed by Nurse Practitioners (NPs) that addressed barriers to access. The aim of this study was to evaluate the outcomes and impact the IACS initiative had on the communities and residents of Northern Alberta. This article describes the initiative design, implementation, outcomes, and impact of the initiative. Methods The IACS model was implemented in a total of 36 visited communities in Northern Alberta from December 2020 to December 2021. The impact of the IACS initiative was measured using a mixed methods approach. The participation rate, cancer screening overdue status, and connection to a PCP were assessed using quantitative data collected through the existing clinical information system. Patient and provider feedback were collected from opened-ended surveys, and all data was analyzed by the research team. This study evaluated the impact the IACS initiative had on patient cancer screening participation and cancer screening knowledge, addressing known barriers to service delivery in rural and remote Northern Alberta, and to understand how this service might be sustained for future operation. Results Six hundred fifty-three people participated in screening offered through the IACS initiative. 99% of Pap screenings offered to patients were accepted, and 98% of FIT kits were accepted from the NPs, with a completion rate of 84%. The clinical data and survey responses from patients and providers indicated support for sustaining the IACS initiative. The IACS model of screening was favoured by most female patients. It also increased screening uptake in the communities we visited in the North Zone of Alberta, where screening rates are low. Conclusion These findings highlight that the IACS initiative was well-received and brought value to underserved communities in Northern Alberta. The IACS model effectively facilitated screening for those who were overdue or have never been screened before. The reach of the IACS model was broader than anticipated, with those who are attached to a PCP also finding the integrated mobile screening model beneficial, bringing the services closer to home.
An environmental scan of financial incentives to increase access to healthy foods: How, how much, and how often?
(2025-02-19) Quach, Anita; Yohannes, Sabrina; Olstad, Dana L.; Campbell, David J.; Corrigan, Crystal; Beall, Reed F.
Highlights This environmental scan identified four main incentive structures for promoting healthy food purchases: price discounts, food vouchers, rewards, and hybrid structures. The median weekly incentive value across all programs was $14.38 USD, with significant variation. Incentives were most commonly distributed on a weekly basis (29%). Few programs provided evidence-based justifications for their chosen incentive structures, values, or distribution frequencies. Further research is needed to directly compare the effectiveness of different incentive structures, values, and frequencies in promoting healthier food purchases.
The RAD51C-XRCC3 Homologous Recombination Repair Complex: Structural Basis for its Interactions and Cancer Associated Mutations
(2025-02-19) Pepper, Jordan Tan; Williams, Gareth; Schriemer, David C.; Lees-Miller, Susan
The RAD51 paralogs are crucial proteins involved in the repair of double-stranded DNA breaks (DSBs) via homologous recombination repair (HRR). There are six human RAD51 paralogs, RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1, and mutations in these genes are associated with cancer and other diseases. The RAD51 paralogs operate as discrete multi-protein complexes whose functional roles and structures are not fully understood. A key RAD51 paralog complex is the RAD51C-XRCC3 heterodimer (CX3), which is the focus of this thesis. I used biochemical, structural, and computational approaches to 1) profile disease and cancer-linked missense mutations found in RAD51C in the context of CX3, 2) determine the structural details of human CX3, and 3) identify and characterize potential CX3 protein interaction partners. I used the Alvinella pompejana ortholog of CX3 to investigate the impact of 5 different cancer associated missense mutations of human RAD51C on protein stability and biochemistry using heterologous expression and purification, mass photometry, fluorescence polarization assays, molecular dynamics simulations, and in silico mutation stability calculators. To investigate human CX3, I used a combination of small-angle X-ray scattering, cross-linking mass-spectrometry, structural prediction models and analysis to uncover features of how RAD51 family members interact with one another. Finally, I used affinity-purification and mass-spectrometry proteomics to detect possible CX3 protein-protein interaction partners, which I then attempted to verify using fluorescence-detection size-exclusion chromatography, with post-hoc analysis of candidate interaction partners using AlphaFold 3 and in silico calculation of interprotein energetics and affinity. From this work, I uncover insights in the structure of the CX3 complex, its possible roles in HRR, and a pathway towards characterizing it in association with interaction partners.
Parallels and Divergences in Multisystem Proteinopathy Genes: Stress Granules, Autophagy, and Myogenic Deficits
(2025-01-31) Pontifex, Carly Sabine; Pfeffer, Gerald; Whelan, Patrick; Shutt, Timothy; Corcoran, Jenn; Milone; Margherita; Greenway; Clive, Steven
Multisystem Proteinopathy (MSP) is a disease that causes some combination of inclusion body myopathy with rimmed vacuoles, Paget’s disease of bone, and ALS/FTD. Several different genes give rise to the unique phenotypic expression of MSP. Given the variety of genes that cause MSP and the specificity of the phenotype and tissue involvement, we asked; what are the unifying pathogenic features of MSP? To address this, we examined three areas of interest: stress granules, autophagy, and myogenesis. The currently identified roster of MSP genes have several structural and functional commonalities which fall into two categories: LC3B-intracting domain containing autophagy adaptors (SQSTM1, VCP, OPTN) and prion-like domain containing stress granule proteins (HNRNPA2B1, HNRNPA1, MATR3, TIA1). Previous studies identified that a non-pathogenic variant of the non-classical MSP protein, TIA1 N357S , can act as a phenotype modifier with SQSTM1P392L leading to distal muscle weakness rather than proximal muscle weakness seen with monogenic SQSTM1 mutations. Here we show that the same TIA1 variant is able to act as a modifier with VCP R159H to produce the same distal weakness. We established three major findings: 1) The non-classical MSP gene TIA1 N357S can modify the myopathy phenotype of both VCP and SQSTM1 to produce distal rather than proximal muscle weakness at the onset of disease, and that TIA1b expression drives the increase of TIA1 expression in diseased muscle and also fails to colocalize with SQSTM1—implying that upregulation of TIA1b is important for muscle stress response and also that TIA1b stress granules have reduced clearance by autophagy. 2) VCP and SQSTM1 both exhibit lysosome accumulation, which may be an emergent feature of inclusion body myopathies. 3) Impaired myogenesis via resistance to the master regulator of myogenesis MyoD, is a feature of MSP.