Porcine reproductive and respiratory syndrome: characteristic features of the infected fetus

Pregnant gilts were infected at 90 days of gestation with porcine reproductive and respiratory virus (PRRSV) isolate SD-23983. Fetuses recovered between 109 and 112 days of gestation were analyzed for the presence of PRRSV. The results showed that not all fetuses were infected, and that infected fetuses tended to be clustered within the uterine horns, suggesting that virus is spread from fetus to fetus. Even though affected litters exhibited different degrees of gross pathology, the presence of an anatomical abnormality was not an identifier of an infected fetus. Analysis of virus replication in individual tissues identified the thymus as the principal site of PRRSV replication. The results show that PRRSV infection in the developing fetus follows a unique course and that PRRSVinduced alterations may be the result of the effect of PRRSV on maternal tissues. These factors need to be taken into consideration when diagnosing PRRSV infection as the cause for aborted and stillborn fetuses.; Swine Day, 2005, Kansas State University, Manhattan, KS, 200

Deterring Inefficient Pharmaceutical Litigation: An Economic Rationale for the FDA Regulatory Compliance Defense

This Article examines the interaction between direct regulation of pharmaceuticals under the Federal Food Drug and Cosmetic Act (FDCA) and the indirect regulation of pharmaceuticals provided by common law tort incentives. The Article concludes that tort liability is generally inappropriate in cases where manufacturers have complied with the FDCA. The Article begins with a description of the FDCA's operation, and provides an overview of the Food and Drug Administration's (FDA) role in the drug approval process and drug labeling. This overview will demonstrate the need for centralized control over drug labeling. Moreover, we will provide an explanation of the costs and benefits of the drug approval process. Next, we will focus on the regulatory effects of tort law from an economics perspective. The role of tort law in deterring inefficient accidents depends on the extent and stringency of government regulation. We will examine the sufficiency of regulatory deterrence under various regulatory schemes, including the FDCA. This economic analysis will demonstrate that tort law's applicability should be limited to those regulatory schemes that inadequately deter risks. Since the FDCA adequately deters risk, the proper role for tort law should be to provide incentives for ensuring regulatory compliance. We then provide a critical review of the legal rules applied to pharmaceutical litigation in American courts. The uncertainty present in current pharmaceutical litigation stems largely from the failure to adopt regulatory compliance in a strict liability world.Examination of labeling litigation suggests that courts have yet to establish meaningful standards. In addition, design defect litigation, by protecting only those drugs without side-effects, leads to untoward consequences. Furthermore, the tort system has a propensity for error. Our current litigation system generates perverse incentives, which we document. Finally, we conclude that because of the strict nature of the FDCA, the role of tort liability should be limited through federal legislation

Conservation of the Gharial (Gavialis gangeticus) at the Madras Crocodile Bank Trust, Chennai, India

Gavialis gangeticus are in serious decline in the wild. In this short article we provide an overview of Gharial ecology and current conservation measures taking place at the Madras Crocodile Bank Trust in India

Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease

BACKGROUND: The objective of this study was to develop and psychometrically evaluate a general measure of patients' satisfaction with medication, the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: The content and format of 55 initial questions were based on a formal conceptual framework, an extensive literature review, and the input from three patient focus groups. Patient interviews were used to select the most relevant questions for further evaluation (n = 31). The psychometric performance of items and resulting TSQM scales were examined using eight diverse patient groups (arthritis, asthma, major depression, type I diabetes, high cholesterol, hypertension, migraine, and psoriasis) recruited from a national longitudinal panel study of chronic illness (n = 567). Participants were then randomized to complete the test items using one of two alternate scaling methods (Visual Analogue vs. Likert-type). RESULTS: A factor analysis (principal component extraction with varimax rotation) of specific items revealed three factors (Eigenvalues > 1.7) explaining 75.6% of the total variance; namely Side effects (4 items, 28.4%, Cronbach's Alpha = .87), Effectiveness (3 items, 24.1%, Cronbach's Alpha = .85), and Convenience (3 items, 23.1%, Cronbach's Alpha = .87). A second factor analysis of more generally worded items yielded a Global Satisfaction scale (3 items, Eigenvalue = 2.3, 79.1%, Cronbach's Alpha = .85). The final four scales possessed good psychometric properties, with the Likert-type scaling method performing better than the VAS approach. Significant differences were found on the TSQM by the route of medication administration (oral, injectable, topical, inhalable), level of illness severity, and length of time on medication. Regression analyses using the TSQM scales accounted for 40–60% of variation in patients' ratings of their likelihood to persist with their current medication. CONCLUSION: The TSQM is a psychometrically sound and valid measure of the major dimensions of patients' satisfaction with medication. Preliminary evidence suggests that the TSQM may also be a good predictor of patients' medication adherence across different types of medication and patient populations

Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group

PURPOSE: An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1–42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. METHODS: This phase II trial included patients with locally advanced, potentially resectable esophageal cancer. All were to receive the above regimen with modifications of carboplatin AUC = 4 and amifostine 500 mg subcutaneously before radiation. All were then to undergo an esophagectomy. A planned interim toxicity analysis after the first 10 patients was to determine whether the carboplatin dose should escalate to AUC = 6. RESULTS: Ten patients were enrolled, and all required dose reductions/omissions during neoadjuvant therapy. One patient died from paclitaxel anaphylaxis. Six patients manifested a complete pathologic response. CONCLUSION: With this regimen, carboplatin AUC = 4 for patients with locally advanced esophageal cancer is appropriate

Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells

Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the time of new diagnosis or at relapse, but there are major limitations with current methods for determining drug sensitivity ex vivo. Here, we describe a functional precision medicine method using a fluorescence imaging platform to test drug sensitivity profiles of primary ALL cells. Leukemia cells are co-cultured with mesenchymal stromal cells and tested with a panel of 40 anti-leukemia drugs to determine individual patterns of drug resistance and sensitivity ("pharmacotype"). This imaging-based pharmacotyping assay addresses the limitations of prior ex vivo drug sensitivity methods by automating data analysis to produce high-throughput data while requiring fewer cells and significantly decreasing the labor-intensive time required to conduct the assay. The integration of drug sensitivity data with genomic profiling provides a basis for rational genomics-guided precision medicine. Key features Analysis of primary acute lymphoblastic leukemia (ALL) blasts obtained at diagnosis from bone marrow aspirate or peripheral blood. Experiments are performed ex vivo with mesenchymal stromal cell co-culture and require four days to complete. This fluorescence imaging-based protocol enhances previous ex vivo drug sensitivity assays and improves efficiency by requiring fewer primary cells while increasing the number of drugs tested to 40. It takes approximately 2-3 h for sample preparation and processing and a 1.5-hour imaging time. Graphical overview

Extraformational sediment recycling on Mars

Extraformational sediment recycling (old sedimentary rock to new sedimentary rock) is a fundamental aspect of Earth's geological record; tectonism exposes sedimentary rock, whereupon it is weathered and eroded to form new sediment that later becomes lithified. On Mars, tectonism has been minor, but two decades of orbiter instrument-based studies show that some sedimentary rocks previously buried to depths of kilometers have been exposed, by erosion, at the surface. Four locations in Gale crater, explored using the National Aeronautics and Space Administration's Curiosity rover, exhibit sedimentary lithoclasts in sedimentary rock: At Marias Pass, they are mudstone fragments in sandstone derived from strata below an erosional unconformity; at Bimbe, they are pebble-sized sandstone and, possibly, laminated, intraclast-bearing, chemical (calcium sulfate) sediment fragments in conglomerates; at Cooperstown, they are pebble-sized fragments of sandstone within coarse sandstone; at Dingo Gap, they are cobble-sized, stratified sandstone fragments in conglomerate derived from an immediately underlying sandstone. Mars orbiter images show lithified sediment fans at the termini of canyons that incise sedimentary rock in Gale crater; these, too, consist of recycled, extraformational sediment. The recycled sediments in Gale crater are compositionally immature, indicating the dominance of physical weathering processes during the second known cycle. The observations at Marias Pass indicate that sediment eroded and removed from craters such as Gale crater during the Martian Hesperian Period could have been recycled to form new rock elsewhere. Our results permit prediction that lithified deltaic sediments at the Perseverance (landing in 2021) and Rosalind Franklin (landing in 2023) rover field sites could contain extraformational recycled sediment.With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737

A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling

A BAFF receptor mutation associated with non-Hodgkin lymphoma provides new insight into the proximal players of normal BAFF-R signaling

Herpetological observations from field expeditions to North Karnataka and Southwest Maharashtra, India

The Western Ghats of India are one of the 34 global hotspots of biodiversity. They are one of the most important large natural areas in the world and are fast becoming recognised for their biological importance. The herpetofauna of the Western Ghats is hugely diverse, with many species exhibiting rare, endemic styles of autecology and niche preference that could equal that of countries such as Borneo and Madagascar. In this report we detail 18 amphibian and 37 reptile species from eight sites following three expeditions to the Western Ghats from 2007-2009. The report details species descriptions, habitat, ecology and conservation to alert the herpetological community to the importance of future research to address the lack of knowledge in species ecology. It also presents newinformation on species distribution and behaviour