Brincidofovir (BCV) is an investigational lipid conjugate of the nucleotide analog cidofovir (CDV), which is being developed as a medical countermeasure for the treatment of smallpox. BCV is active against double-stranded DNA viruses including BK and JC viruses. Here, we validated procedures for quantifying BCV and its pharmacologically active moiety cidofovir diphosphate (CDV-PP) in mouse kidney, brain and spleen tissue homogenates. Following homogenization, BCV and CDV-PP were extracted from the tissues by protein precipitation with their stable, isotopically labeled internal standards, BCV-d6 and 13 C315 N2 -CDV-PP. Then, samples were analyzed for BCV by reverse-phase chromatography on a Waters Xterra MS C18 (50 × 2.1 mm, 3.5 μm particle size) column while CDV-PP was analyzed on a Thermo BioBasic AX (50 × 2.1 mm, 5 μm particle size) column using anion exchange chromatography. Detection was achieved by electrospray ionization in positive ion mode on an AB Sciex API-5000 triple quadrupole mass spectrometer. The calibration curves were linear over a range of 1.00-1,000 ng/ml homogenate and 0.050-50.0 ng/ml homogenate for BCV and CDV-PP, respectively. These methods were validated according to US Food and Drug Administration guidance for industry and may be used to characterize the tissue pharmacology of both analytes to advance its preclinical development.Free-roaming domestic dogs in Indigenous communities of northern Australia have the potential to spread diseases at the wild-domestic dog interface. Hunting activities with domestic dogs, commonly practiced in Indigenous communities, also create opportunities for wild-domestic dog interactions in the bush, providing pathways for potential disease spread. Data from a camera-trap study conducted in remote Indigenous communities of northern Australia were used to explore spatial and seasonal opportunities for interactions between dingoes and unsupervised domestic dogs. For each type of dog, activity indices, based on detection events per camera station with an adjustment for sampling effort, were mapped across the study area and plotted against distance to communities. Unsupervised domestic dogs were mostly active in proximity (10 km) to communities during the wet season. Overall, our findings suggest that interactions between dingoes and unsupervised community dogs are more likely to occur around the communities, particularly during the dry season, whereas in the wet season, there is increased opportunity for interactions in distant areas in the bush between dingoes and, presumably, hunting dogs.A 38-year-old white rhinoceros bull (Ceratotherium simum) was treated with phenylbutazone over a period of four years for chronic osteoarthritic and neuropathic pain of the thoracic limbs. Initially the lameness was sporadic and responded well to phenylbutazone (4 mg/kg PO SID). The lameness increased in severity during the winter months. Four years after treatment was initiated, there was an increase in the severity and incidence of the lameness. Analgesia was augmented by the addition of non-conventional analgesic drugs. Pentosan polysulfate was administered IM at 3 mg/kg once a week for two treatments and thereafter monthly when possible. Gabapentin was used at 8 mg/kg but produced ataxia and anorexia. The dose was reduced to 4-5 mg/kg PO SID. Amantadine (3 mg/kg PO BID) was added to the multimodal analgesia and produced a significant improvement in the clinical lameness. Chronic inflammation was monitored using both automated and manual fibrinogen methods. Eventually the rhinoceros was euthanized on humane grounds when treatment was unable to produce suitable clinical relief.Over the years, industrial safety regulation has shifted from a "hard" command and control regime to a "soft" regime. A "hard" regime includes the use of strict prescriptive requirements which explain how industry should solve particular issues.  https://www.selleckchem.com/erk.html  A "soft" regime, uses more functional requirements, pointing out what goals are to be achieved. In a "soft" regime, prescriptive standards might still exist, but they are considered suggested solutions, with alternative solutions also being considered if they achieve the overall regulatory goals. The purpose of such a shift is to create regulations that are more flexible, meaning that they are more open for the use of novel technology and for the use of risk assessments as a basis for decision making. However, it is not clear that the shift from a hard to a soft regime has made it easier to use risk assessments for such a purpose in practice. In the present article, we discuss the limitations caused by strict adherence to prescriptive requirements presented in standards or regulations and present our perspective on why and how these can limit risk management in practice. The article aims to discuss the strengths and weaknesses, with regard to risk management, when regulations are strictly dependent on prescriptive or specification-based standards and guidelines. Several examples are used to illustrate some of the main challenges related to the use of specification-based technical standards and how the regulatory shift from "hard" to "soft" has not necessarily made it easier to implement technological solutions based on risk assessments.Fathers' involvement in early childhood is important for children's physical, emotional, and cognitive development, particularly in low-income families. However, little is known about the longitudinal relations between early father involvement and children's later physiological responses to chronic stress and behaviors impacted by stress in the context of poverty. These issues are particularly important among Latinx immigrant families who face significant psychosocial and poverty-related risk. In the current study, we examined the relationship between father involvement in infancy and physiological chronic stress in the middle childhood period, as measured through hair cortisol concentration (HCC), and several behavioral measures (attention problems, working memory) in a Latinx immigrant sample with low income. Father involvement in infancy predicted children's later HCC, and working memory in second to third grade. Father involvement also moderated the effect of HCC on working memory, such that increased HCC predicted better working memory when fathers were not involved.