Analgesic management of an eight-year-old Springer Spaniel after amputation of a thoracic limb

Analgesic agents were administered perioperatively to an eight-year-old Springer Spaniel undergoing amputation of its right thoracic limb. The amputation was carried out due to a painful, infiltrative and poorly differentiated sarcoma involving the nerves of the brachial plexus. A combination of pre-emptive and multimodal perioperative analgesic strategies was used; including intravenous (IV) infusions of fentanyl, morphine, lidocaine and ketamine

The Novel Deacetylase Inhibitor AR-42 Demonstrates Pre-Clinical Activity in B-Cell Malignancies In Vitro and In Vivo

While deacetylase (DAC) inhibitors show promise for the treatment of B-cell malignancies, those introduced to date are weak inhibitors of class I and II DACs or potent inhibitors of class I DAC only, and have shown suboptimal activity or unacceptable toxicities. We therefore investigated the novel DAC inhibitor AR-42 to determine its efficacy in B-cell malignancies.In mantle cell lymphoma (JeKo-1), Burkitt's lymphoma (Raji), and acute lymphoblastic leukemia (697) cell lines, the 48-hr IC(50) (50% growth inhibitory concentration) of AR-42 is 0.61 microM or less. In chronic lymphocytic leukemia (CLL) patient cells, the 48-hr LC(50) (concentration lethal to 50%) of AR-42 is 0.76 microM. AR-42 produces dose- and time-dependent acetylation both of histones and tubulin, and induces caspase-dependent apoptosis that is not reduced in the presence of stromal cells. AR-42 also sensitizes CLL cells to TNF-Related Apoptosis Inducing Ligand (TRAIL), potentially through reduction of c-FLIP. AR-42 significantly reduced leukocyte counts and/or prolonged survival in three separate mouse models of B-cell malignancy without evidence of toxicity.Together, these data demonstrate that AR-42 has in vitro and in vivo efficacy at tolerable doses. These results strongly support upcoming phase I testing of AR-42 in B-cell malignancies

Longer and better lives for patients with atrial fibrillation:the 9th AFNET/EHRA consensus conference

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF

Fifty Years of Urban Accessibility: The Impact of Urban Railway Network on the Land Gradient in Industrializing Berlin

As the first to use an archival data set on historical land values of Berlin, Germany, from 1890 to 1936, we exploit exogenous variation in transport technology in order to test the validity of the monocentric city model. Endogenously determining the CBD, we conduct cross-section and time-difference analysis and model the land gradient in terms of straight-line distance and travel times. A counterfactual scenario indicates that a large proportion of urban decentralization is attributable to improvements in transport infrastructure. Controlling for spatial dependency, results suggest that the monocentric model fitted the city structure until the mid 20th century

On the brink of explosion? Identifying the source and potential spread of introduced Zosterops white-eyes in North America

Understanding the source of non-native introduced populations is crucial for forecasting geographic invasion potential and understanding the ecological consequences of potential establishment. Here we use genomics to identify the source populations and invasion dynamics of two non-native introduced populations from the iconic avian lineage of ‘great speciators’ known as white-eyes (genus Zosterops). We established confidently for the first time that introduced Zosterops populations in Hawaii and southern California are completely unrelated and derived from independent introductions of the species Z. japonicus and Z. simplex, respectively. We used descriptive population genetic statistics to identify a reduction in genetic diversity and increase in private alleles in the southern California population supporting a recent, potentially ongoing, genetic bottleneck in this population. In contrast, the introduced population in Hawaii showed no such characteristics, likely due to a larger founding population size and repeated introductions in this intentionally introduced population. Ecological niche modeling indicated that there is little environmentally suitable habitat for Z. simplex across the continent of North America, suggesting limited invasion potential, assuming niche conservatism. Yet, portions of the introduced Z. simplex population have already surpassed areas projected as suitable, likely because the urbanized environment of southern California offers biotic resources and microhabitats not captured by our model. Because Z. simplex appears to have overcome both the ‘invasion paradox’ of low founding genetic diversity and relatively unfamiliar environmental conditions in southern California, we suggest that this population may continue expanding beyond our environmental niche model projections in other temperate, urban regions