Rethinking the uncertainty of African swine fever virus contamination in feed ingredients and risk of introduction into the United States

Economically relevant pathogens, such as African swine fever virus (ASFV), have been shown to survive when experimentally inoculated in some feed ingredients under the environmental conditions in transoceanic transport models. However, these models did not characterize the likelihood of virus survival under various time and temperature processes that feed ingredients undergo before they are added to swine diets. Here, we developed a quantitative risk assessment model to estimate the probability that one or more corn or soybean meal ocean vessels (25,000 tonnes) contaminated with ASFV would be imported into the United States annually. This final probability estimate was conditionally based on five likelihoods: the probability of initial ASFV contamination (p0), ASFV inactivation during processing (p1) and transport (p2), recontamination (pR), and ASFV inactivation while awaiting customs clearance at United States entry (p3). The probability of ASFV inactivation was modelled using corn and soybean (extruded or solvent extracted) processing conditions (times and temperatures), D-values (time to reduce 90% or 1-log) estimated from studies of ASFV thermal inactivation in pork serum (p1), and survival in feed ingredients during transoceanic transport (p2 and p3). ‘What-if’ scenarios using deterministic values for p0 and pR (1%, 10%, 25%, 50%, 75%, and 100%) were used to explore their impact on risk. The model estimated complete inactivation of ASFV after extrusion or solvent extraction processes regardless of the initial ASFV contamination probability assumed. The value of recontamination (ranging from 1% to 75%) was highly influential on the risk of one ASFV-contaminated soybean meal vessel entering the United States. Median risk estimates ranged from 0.064% [0.006%–0.60%; 95% probability interval (PI)], assuming a pR of 1.0%, up to 4.67% (0.45%–36.50% 95% PI) assuming a pR of 75.0%. This means that at least one vessel with ASFV-contaminated soybean meal would be imported once every 1563–21 years, respectively. When all raw corn was assumed to be contaminated (p0 = 100%), and no recontamination was assumed to occur (pR = 0%), the median probability of one vessel with ASFV-contaminated corn entering the United States was 2.02% (0.28%–9.43% 95% PI) or once every 50 years. Values of recontamination between 1% and 75% did not substantially change the risk of corn. Days of transport, virus survival during transport (D-value), and number of vessels shipped were the parameters most influential for increased likelihood of a vessel with ASFV-contaminated soybean meal or corn entering the United States. The model helped to identify knowledge gaps that are most influential on output values and serves as a framework that could be updated and parameterized as new scientific information becomes available. We propose that the quantitative risk assessment model developed in this study can be used as a framework for estimating the risk of ASFV entry into the United States and other ASFV-free countries through other types of imported feed ingredients that may potentially become contaminated. Ultimately, this model can be used to develop risk mitigation strategies and critical control points for inactivating ASFV during feed ingredient processing, storage, and transport, and contribute to the design and implementation of biosecurity measures to prevent the introduction of ASFV into the United States and other ASFV-free countries.     

Enhanced UV-Induced Skin Carcinogenesis in Transgenic Mice Overexpressing Proprotein Convertases

The proprotein convertases (PCs) furin and PACE4 process numerous substrates involved in tumor growth, invasion, and metastasis. We have previously shown that PCs increase the susceptibility to chemical skin carcinogenesis. Because of the human relevancy of UV radiation in the etiopathogenesis of human skin cancer, we investigated whether or not transgenic mice overexpressing either furin alone or both furin and PACE4 show increased susceptibility to UV carcinogenesis. After backcrossing our previously described furin and PACE4 transgenic lines, targeted to the epidermis, into a SKH-1 background, we exposed both single and double transgenic mice to UV radiation for 34 weeks. The results showed an increase in squamous cell carcinoma (SCC) multiplicity of approximately 70% in the single furin transgenic mouse line SF47 (P < .002) and a 30% increase in the other single transgenic line SF49 when compared to wild-type (WT) SKH-1 mice. Interestingly, there was also an increase in the percentage of high histologic grade SCCs in the transgenic lines compared to the WT mice, i.e., WT = 9%, SF47 = 15%, and SF49 = 26% (P < .02). Targeting both furin and PACE4 to the epidermis in double transgenic mice did not have an additive effect on tumor incidence/multiplicity but did enhance the tumor histopathologic grade, i.e., a significant increase in higher grade SCCs was seen in the bigenic mouse line SPF47 (P < .02). Thus, we observed an increased susceptibility to UV in single furin transgenic mice that was not substantially enhanced in the double furin/PACE4 transgenic mice.     

Acute cortisol release during stereotactic fractionated radiotherapy to an ACTH-secreting pituitary macroadenoma

A 33-year old male was diagnosed with Cushing’s disease due to a large and invasive ACTH-secreting macroadenoma. After surgical failure ketoconazole therapy was initiated to control cortisol hypersecretion and his symptoms. He was referred to radiotherapy, and fractionated stereotactic radiotherapy in 30 fractions was delivered. After 12 daily fractions of radiotherapy the urinary cortisol release increased abruptly together with clinical deterioration. The daily ketoconazole dose was increased, and 10 days after concluding radiotherapy his urinary cortisol returned to normal values. Hormonal remission was observed less than 1 year following radiotherapy.

     

Velopharyngeal insufficiency as the initial manifestation of a Myotonic Dystrophy type 1: A case report

Velopharyngeal insufficiency (VPI) is a disorder affecting nasal resonance during speech. The most common cause of VPI is a cleft palate. However, VPI can occur as a consequence of a neuromuscular or neurologic disorder without a palatal malformation. Myotonic Dystrophy type 1 is a hereditary muscular disorder. In these cases, the abnormality is located on the 19q13.3 region, including a myotonic dystrophy protein kinase CTG repeat. This disease has several clinical manifestation features depending of the number of CTG repeats. The myotonic dystrophy can affect several muscle groups. VPI associated with the involvement of the velopharyngeal muscles, has been reported as the main clinical feature in some cases. The purpose of this paper is to present a case of VPI as the main clinical manifestation in a patient with a Myotonic Dystrophy type 1.     

Improving the Power of an Efficacy Study of a Social and Emotional Learning Program: Application of Generalizability Theory to the Measurement of Classroom-Level Outcomes

Social and emotional learning programs are designed to improve the quality of social interactions in schools and classrooms in order to positively affect students’ social, emotional, and academic development. The statistical power of group randomized trials to detect effects of social and emotional learning programs and other preventive interventions on setting-level outcomes is influenced by the reliability of the outcome measure. In this paper, we apply generalizability theory to an observational measure of the quality of classroom interactions that is an outcome in a study of the efficacy of a social and emotional learning program called The Recognizing, Understanding, Labeling, Expressing, and Regulating emotions Approach. We estimate multiple sources of error variance in the setting-level outcome and identify observation procedures to use in the efficacy study that most efficiently reduce these sources of error. We then discuss the implications of using different observation procedures on both the statistical power and the monetary costs of conducting the efficacy study.