Screening for hepatocellular carcinoma: patient selection and perspectives

Hepatocellular carcinoma (HCC) develops on the background of liver cirrhosis often from multiple, simultaneous factors. The diagnosis of a single small HCC comes with good prognosis and provides a potential for cure. In contrast, the diagnosis of multifocal, large HCC has high mortality and poor prognosis. Unfortunately, the majority of HCC is diagnosed at such late stages. A surveillance program endorsed by regional liver societies involves six-monthly ultrasound surveillance of at-risk patients. This had been in action for the last two decades. It has led to marked increase in the proportion of patients presenting with small unifocal nodules found on surveillance. The development of tools to enhance our ability in optimizing available surveillance is likely to improve the prognosis of patients with HCC. In this review, we discuss the difficulties in utilizing HCC surveillance and possible means of improvement

Marketing Orientation: A Longitudinal Study of Community Banks

Marketing orientation has long been touted as a means of improved business performance and a key to success in marketing management (Kotler, Keller & Chernev, 2021). This is a longitudinal study of community banks examining marketing orientation and business performance using a survey instrument based on the work of Narver and Slater (1990) and Kohli and Jaworski (1990). Four survey datasets cover the period preceding the Great Recession (2003-2005), the Great Recession and its fallout (2008-2010), a Post–Great Recession period (2014-2016), and the COVID-19 period (2020). Survey responses were gathered from a selected set of community bank CEOs in the Southeastern U.S. In addition to survey items about the organization\u27s marketing orientation, bank financial information was collected regarding assets and profits for each year in the study periods. Kohli and Jaworski (1990) make the point that business performance is responsive to changing external conditions. This study includes unemployment, GDP growth, inflation, labor participation rate, and the 10-year U.S. Treasury yield for its direct impact on bank performance. Research questions focus on variations in the bank\u27s approach to market orientation across the selected four economic periods. Do banks change their marketing orientation when economic conditions change? Do banks emphasize different variables in marketing orientation (customer, competitors, market planning) based on economic conditions? Does the relationship between marketing orientation and the bank\u27s financial performance change between the four economic periods

Exposure and susceptibility of inactive and abandoned tailings to flash floods in Chile

The 2020 Global Industry Standard on Tailings Management exemplifies the move to reduce risks posed by tailings worldwide. However, inadequate attention focuses on various non-active tailings, which may ultimately become the responsibility of national or state regulators. This challenge is particularly evident in Chile, which hosts 467 inactive and 173 abandoned tailings according to Chile’s National Geology and Mining Service (SERNAGEOMIN). The two drivers of tailings failures globally are heavy precipitation and seismic activity. In Chile, from 1915 to 2010, earthquakes accounted for about 80 per cent of recorded major tailings failures, with heavy rainfall mainly responsible for the remainder. Since 2015, however, there have been several extreme rainfall and associated flash flood events in northern Chile that have mobilized tailings. Events in 2015 and 2017 have been analyzed remotely to understand the mechanisms and magnitudes of tailings erosion and mobilization. The 24–26 March 2015 intense rainfall event most affected the Salado river basin and led to significant modification of the tailings beach at Chañaral in the Atacama Region. At least several 100 000 m3 of tailings were scoured from the beach and transported into coastal water. Another inundation event on 11–13 May 2017 caused erosion, undercutting and partial collapse of several inactive and abandoned tailings deposits along the Marquesa river channel, which is a tributary of the Elqui river in the Coquimbo Region. The total volume of missing tailings is of the order of 100 000 m3 . These volumes are of magnitudes equivalent to those reported for some of the most significant tailings failures in Chile and highlight the urgency to systematically assess the exposure of Chile’s tailings to floods, particularly in the context of changing climate and weather patterns

Healthcare costs of transarterial chemoembolization in the treatment of hepatocellular carcinoma

Background: A meta-analysis comparing drug-eluting beads transarterial chemoembolization (DEB-TACE) with conventional transarterial chemoembolization (cTACE) has recently been published. On balance, no significant differences were found in terms of objective response and overall survival. The impact on healthcare costs had been studied in small series based on a hypothetical model and was in favor of DEB-TACE. We aimed to evaluate and compare healthcare costs and effectiveness of both modalities in a cohort of patients from Nottingham, UK. Methods: Using a dedicated radiology database, we identified all patients who had undergone cTACE or DEB-TACE between 2006 and 2012 at a single tertiary referral center based in Nottingham. We collected clinical data, including treatment response, postprocedure complications and 30-day mortality. Costing models were constructed to present both our local hospital perspective as well as the national health service position. Results: During our study period, 101 procedures were performed on 43 patients (76 cTACE procedures on 26 patients and 25 DEB-TACE procedures on 17 patients). Overall, 11/26 in cTACE and 5/17 in DEB-TACE group had progressive disease (p=0.52). Adverse events were seen in 6/76 cTACE compared with 7/25 DEB-TACE group (p=0.16). Based on the predetermined standard pathway there was an unadjusted average cost difference of £3770.30 (TACE =£9070.44, DEB-TACE =£5300.14) in favor of the DEB-TACE. Results from our costing models indicated a £2715.33 (95% CI £580.88–4849.77) cost difference in favor of the same procedure. Conclusions: Even when the extra costs of DEB-TACE were considered, the overall treatment costs per patient were lower in relation to cTACE

Accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host

<p>Abstract</p> <p>Background</p> <p>In order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the VRQ allele of the PrP gene were infected by the oral route. Infection occurred in all lambs with a remarkably short and highly consistent incubation period of approximately 6 months. Challenge of lambs at approximately eight months of age resulted in disease in all animals, but with more variable incubation periods averaging significantly longer than those challenged at 14 days.</p> <p>This model provides an excellent system in which to study the disease in the natural host by virtue of the relatively short incubation period and close resemblance to natural infection.</p> <p>Results</p> <p>Multiple sites of prion uptake were identified, of which the most important was the Peyer's patch of the distal ileum.</p> <p>Neuroinvasion was detected initially in the enteric nervous system prior to infection of the central nervous system. At end stage disease prion accumulation was widespread throughout the entire neuraxis, but vacuolar pathology was absent in most animals that developed disease at 6–7 months of age.</p> <p>Conclusion</p> <p>Initial spread of detectable PrP was consistent with drainage in afferent lymph to dependent lymph nodes. Subsequent accumulation of prions in lymphoid tissue not associated with the gut is consistent with haematogenous spread. In addition to macrophages and follicular dendritic cells, prion containing cells consistent with afferent lymph dendritic cells were identified and are suggested as a likely vehicle for carriage of prions from initial site of uptake to the lymphoreticular system, and as potential carriers of prion protein in blood. It is apparent that spongiform change, the characteristic lesion of scrapie and other prion diseases, is not responsible for the clinical signs in sheep, but may develop in an age dependent manner.</p

The Effects of the Russian Invasion of Ukraine on Exports to Italy

Italy imported 122,000 tons of soft wheat from Ukraine and 72,000 from Russia. During the current events international food and feed prices have increased by 8 to 22% causing mass shortages around the world. On top of the ethical and moral dilemmas of continuing business with Russia, insurance premiums have jumped 400% for doing business with the invading country.https://digitalscholarship.unlv.edu/durep_posters/1106/thumbnail.jp

Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.

COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans

The 2010<i>M</i>_w8.8 Maule, Chile earthquake: Nucleation and rupture propagation controlled by a subducted topographic high

Knowledge of seismic properties in an earthquake rupture zone is essential for understanding the factors controlling rupture dynamics. We use data from aftershocks following the Maule earthquake to derive a three-dimensional seismic velocity model of the central Chile forearc. At 36°S, we find a highvp (&gt;7.0 km/s) and high vp/vs(?1.89) anomaly lying along the megathrust at 25 km depth, which coincides with a strong forearc Bouguer gravity signal. We interpret this as a subducted topographic high, possibly a former seamount on the Nazca slab. The Maule earthquake nucleated at the anomaly's updip boundary; yet high co-seismic slip occurred where the megathrust is overlain by lower seismic velocities. Sparse aftershock seismicity occurs within this structure, suggesting that it disrupts normal interface seismogenesis. These findings imply that subducted structures can be conducive to the nucleation of large megathrust earthquakes, even if they subsequently hinder co-seismic slip and aftershock activity

How Do Collegiate Sport Clubs Achieve Organizational Effectiveness?

A greater understanding of the organizational processes of sport clubs can inform strategies to improve clubs’ organizational effectiveness. This study examined whether sport club capacity and activities influence the organizational effectiveness of collegiate sport clubs. Sport club members (n = 201) completed a questionnaire, with secondary data collected from the university. Regression analysis found club operations, club fiscal responsibility, frequency of club practice, and frequency of competitions significantly, positively predict organizational effectiveness. Comparatively, club human capital and facility quality significantly, negatively predict organizational effectiveness. These results have implications relating to club training, mentorship, resource allocation, and club activities