Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters

<p>Abstract</p> <p>Background</p> <p>The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure.</p> <p>Results</p> <p>The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86).</p> <p>Conclusion</p> <p>A definition of murine histologic alterations resembling asthma in the BALB/c OVA mouse was developed and validated. The definition will be of use in experiments involving this model to ensure that all mice said to have undergone an asthmatic attack did indeed reveal allergic pulmonary inflammation. Proposed grading criteria should be further evaluated with additional studies using physiologic measures of attack severity and increased airway resistance.</p

Understanding Sow Sexual Behavior and the Application of the Boar Pheromone to Stimulate Sow Reproduction

In this chapter, we review the sexual behavior of domestic pigs, and the visible or measurable anatomical features of the pig that will contribute to detecting sows in estrus. We also summarize olfactory organs, and the effects of a sexual pheromone on pig’s biology and sow reproductive performance. We discuss the role of a live boar in the heat detection where the female is in breeding crates. However, there is an increasing interest in being able to breed sows without a boar present. Farm workers must be trained on the fine points of estrus detection so that they can work in a safe and productive setting. After a review of olfactory biology of the pig, the chapter explains how new pheromonal technology, such as BOARBETTER®, aids in the process of heat detection with or without a live boar. To achieve reproductive success, the persons breeding must assimilate all fine points of pig sexual behavior and possess a clear understanding of what they should be looking for in each sow they expect to breed

Review: Transport Losses in Market Weight Pigs: I. A Review of Definitions, Incidence, and Economic Impact

Transport losses (dead and nonambulatory pigs) present animal welfare, legal, and economic challenges to the US swine industry. The objectives of this review are to explore 1) the historical perspective of transport losses; 2) the incidence and economic implications of transport losses; and 3) the symptoms and metabolic characteristics of fatigued pigs. In 1933 and 1934, the incidence of dead and nonambulatory pigs was reported to be 0.08 and 0.16%, respectively. More recently, 23 commercial field trials (n = 6,660,569 pigs) were summarized and the frequency of dead pigs, nonambulatory pigs, and total transport losses at the processing plant were 0.25, 0.44, and 0.69% respectively. In 2006, total economic losses associated with these transport losses were estimated to cost the US pork industry approximately $46 million. Furthermore, 0.37 and 0.05% of the nonambulatory pigs were classified as either fatigued (nonambulatory, noninjured) or injured, respectively, in 18 of these trials (n = 4,966,419 pigs). Fatigued pigs display signs of acute stress (open-mouth breathing, skin discoloration, muscle tremors) and are in a metabolic state of acidosis, characterized by low blood pH and high blood lactate concentrations; however, the majority of fatigued pigs will recover with rest. Transport losses are a multifactorial problem consisting of people, pig, facility design, management, transportation, processing plant, and environmental factors, and, because of these multiple factors, continued research efforts are needed to understand how each of the factors and the relationships among factors affect the well-being of the pig during the marketing process

Reconstructing Disturbances and Their Biogeochemical Consequences over Multiple Timescales

Ongoing changes in disturbance regimes are predicted to cause acute changes in ecosystem structure and function in the coming decades, but many aspects of these predictions are uncertain. A key challenge is to improve the predictability of postdisturbance biogeochemical trajectories at the ecosystem level. Ecosystem ecologists and paleoecologists have generated complementary data sets about disturbance (type, severity, frequency) and ecosystem response (net primary productivity, nutrient cycling) spanning decadal to millennial timescales. Here, we take the first steps toward a full integration of these data sets by reviewing how disturbances are reconstructed using dendrochronological and sedimentary archives and by summarizing the conceptual frameworks for carbon, nitrogen, and hydrologic responses to disturbances. Key research priorities include further development of paleoecological techniques that reconstruct both disturbances and terrestrial ecosystem dynamics. In addition, mechanistic detail from disturbance experiments, long-term observations, and chronosequences can help increase the understanding of ecosystem resilience

Reconstructing Disturbances and Their Biogeochemical Consequences over Multiple Timescales

Ongoing changes in disturbance regimes are predicted to cause acute changes in ecosystem structure and function in the coming decades, but many aspects of these predictions are uncertain. A key challenge is to improve the predictability of postdisturbance biogeochemical trajectories at the ecosystem level. Ecosystem ecologists and paleoecologists have generated complementary data sets about disturbance (type, severity, frequency) and ecosystem response (net primary productivity, nutrient cycling) spanning decadal to millennial timescales. Here, we take the first steps toward a full integration of these data sets by reviewing how disturbances are reconstructed using dendrochronological and sedimentary archives and by summarizing the conceptual frameworks for carbon, nitrogen, and hydrologic responses to disturbances. Key research priorities include further development of paleoecological techniques that reconstruct both disturbances and terrestrial ecosystem dynamics. In addition, mechanistic detail from disturbance experiments, long-term observations, and chronosequences can help increase the understanding of ecosystem resilienc

Temperature correction of spectra to improve solute concentration monitoring by in situ ultraviolet and mid-infrared spectrometries towards isothermal local model performance

Changes in temperature can significantly affect spectroscopic-based methods for in situ monitoring of processes. As varying temperature is inherent to many processes, associated temperature effects on spectra are unavoidable, which can hinder solute concentration determination. Ultraviolet (UV) and mid-infrared (IR) data were acquired for l-ascorbic acid (LAA) in MeCN/H2O (80:20 w/w) at different concentrations and temperatures. For both techniques, global partial least squares (PLS) models for prediction of LAA concentration constructed without preprocessing of the spectra required a high number of latent variables to account for the effects of temperature on the spectra (root mean square error of cross validation (RMSECV) of 0.18 and 0.16 g/100 g solvent, for UV and IR datasets, respectively). The PLS models constructed on the first derivative spectra required fewer latent variables, yielding variable results in accuracy (RMSECV of 0.23 and 0.06 g/100 g solvent, respectively). Corresponding isothermal local models constructed indicated improved model performance that required fewer latent variables in the absence of temperature effects (RMSECV of 0.01 and 0.04 g/100 g solvent, respectively). Temperature correction of the spectral data via loading space standardization (LSS) enabled the construction of global models using the same number of latent variables as the corresponding local model, which exhibited comparable model performance (RMSECV of 0.06 and 0.04 g/100 g solvent, respectively). The additional chemometric effort required for LSS is justified if prediction of solute concentration is required for in situ monitoring and control of cooling crystallization with an accuracy and precision approaching that attainable using an isothermal local model. However, the model performance with minimal preprocessing may be sufficient, for example, in the early phase development of a cooling crystallization process, where high accuracy is not always required. UV and IR spectrometries were used to determine solubility diagrams for LAA in MeCN/H2O (80:20 w/w), which were found to be accurate compared to those obtained using the traditional techniques of transmittance and gravimetric measurement. For both UV and IR spectrometries, solubility values obtained from models with LSS temperature correction were in better agreement with those determined gravimetrically. In this first example of the application of LSS to UV spectra, significant improvement in the predicted solute concentration is achieved with the additional chemometric effort. There is no extra experimental burden associated with the use of LSS if a structured approach is employed to acquire calibration data that account for both temperature and concentration

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals

Losing Our Minds? New Research Directions on Skilled Migration and Development

This paper critiques the last decade of research on the effects of high-skill emigration from developing countries, and proposes six new directions for fruitful research. The study singles out a core assumption underlying much of the recent literature, calling it the Lump of Learning model of human capital and development, and describes five ways that research has come to challenge that assumption. It assesses the usefulness of the Lump of Learning model in the face of accumulating evidence. The axioms of the Lump of Learning model have shaped research priorities in this literature, but many of those axioms do not have a clear empirical basis. Future research proceeding from established facts would set different priorities, and would devote more attention to measuring the effects of migration on skilled-migrant households, rigorously estimating human capital externalities, gathering microdata beyond censuses, and carefully considering optimal policy among others. The recent literature has pursued a series of extensions to the Lump of Learning model. This study urges discarding the Lump of Learning model, pointing toward a new paradigm for research on skilled migration and development