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Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.

The safety and integrity of the blood supply is of paramount importance for delivering optimal medical care. Additionally, blood safety is of utmost importance to the United States public. Pathogen testing of donated blood products has been adapted and developed with the goal of eliminating the risk of transfusion-transmitted infectious disease. Currently, blood safety interventions are focused on excluding persons at risk for transfusion-transmissible infections from donating blood and on detecting the presence of transfusion-transmissible agents in donated blood. These interventions are intended to be complementary and function to isolate, and ideally, eliminate, the risk of exposure to known pathogenic agents by transfused blood components. We provide an overview of the strategies and techniques utilized to ensure the safety of the blood supply in the U.S.

The American Society for Apheresis (ASFA) regularly publishes evidence-based guidelines, with the most recent edition in 2016, to assist the requesting and/or apheresis physicians with the evaluation of therapeutic apheresis. Given that therapeutic plasma exchange (TPE) is one of the most common therapeutic apheresis procedures, in this review, we discuss the rationale of TPE in both ASFA category I (first-line therapy) and II (second-line therapy) indications. However, the ASFA Guidelines usually provide little guidance with regard to scheduling/urgency issues. Given that mobilizing resources to perform apheresis after-hours may be expensive and challenging, we classified the urgency of the procedures in this review into 3 distinct groups: emergent (i.e. TPE should be started as soon as possible, preferably within 4–6 h upon request), urgent (i.e. TPE should be initiated within 24 h of request), and routine (i.e. TPE may be performed during regular working hours) based on our experiences in clinical practices. A brief discussion of the technical aspects as well as important considerations for an apheresis consultation is also provided.

Early warning of post-fire debris-flow occurrence during intense rainfall has traditionally relied upon a library of regionally specific empirical rainfall intensity–duration thresholds. Development of this library and the calculation of rainfall intensity-duration thresholds often require several years of monitoring local rainfall and hydrologic response to rainstorms, a time-consuming approach where results are often only applicable to the specific region where data were collected. Here, we present a new, fully predictive approach that utilizes rainfall, hydrologic response, and readily available geospatial data to predict rainfall intensity–duration thresholds for debris-flow generation in recently burned locations in the western United States. Unlike the traditional approach to defining regional thresholds from historical data, the proposed methodology permits the direct calculation of rainfall intensity–duration thresholds for areas where no such data exist. The thresholds calculated by this method are demonstrated to provide predictions that are of similar accuracy, and in some cases outperform, previously published regional intensity–duration thresholds. The method also provides improved predictions of debris-flow likelihood, which can be incorporated into existing approaches for post-fire debris-flow hazard assessment. Our results also provide guidance for the operational expansion of post-fire debris-flow early warning systems in areas where empirically defined regional rainfall intensity–duration thresholds do not currently exist.

In the southwestern United States, post-fire debris flows commonly initiate during short bursts of intense rainfall. To date, the frequency of the rainfall rates has not been quantified. Here, we combine an existing database of debris-flow occurrences and corresponding peak storm intensities with a geospatial library of rainfall recurrence interval (RI) information and climate type to determine the distribution of the estimated frequencies of the rainfall associated with 316 observed post-fire debris flows in the southwestern United States. Our results indicate that a majority (77%) of the observed debris flows were triggered by rainfall intensities with RI less than 2 years. Climatic and geographic differences in RI were evident in our analysis. Debris flows in most of the analyzed climates within California, Colorado, and New Mexico were primarily associated with 1-year or less RI intensities, whereas debris flows in arid portions of Arizona, Colorado, and Utah tended to be generated during storms greater than 2-year RI. Event consequence, as defined by the impact on downstream communities and infrastructure, was not directly related to RI, as very destructive debris flows were initiated at a wide range of RI intensities. Our results highlight that post-fire debris-flow initiation can be expected during common rainstorms in the southwestern United States, therefore emergency management plans and risk mitigation efforts must focus on both extreme and frequent rainstorms.

Patients receiving ABO-incompatible (ABOi) kidney transplants are treated before and after transplant with combination therapy, such as intravenous immunoglobulin (IVIG) and therapeutic plasma exchange, to prevent allograft rejection by reducing anti-A and anti-B titers. Although generally considered safe, it is well known that commercial IVIG products contain detectable anti-A and anti-B, which can be associated with hemolysis. Different preparative manufacturing techniques during the production of IVIG affect ABO antibody levels in IVIG preparations; therefore, some manufacturers now use new methods to reduce anti-A/B levels at the preproduction stage. The variations in implementing these strategies creates the potential for significant variation in antibody titers between products and, in some cases, even between lots of the same IVIG product. We report a case of persistently elevated anti-A titers in an ABOi kidney transplant recipient associated with elevated ABO antibody titers present in the preparation of IVIG used at our facility.

Drug-associated adverse events cause approximately 30 billion dollars a year of added health care expense, along with negative health outcomes including patient death. This constitutes a major public health concern. The US Food and Drug Administration (FDA) requires drug labeling to include potential adverse effects for each newly developed drug product. With the advancement in incidence of adverse drug events (ADEs) and potential adverse drug events, published studies have mainly concluded potential ADEs from labeling documents obtained from the FDA's preapproval clinical trials, and very few analyzed their research work based on reported ADEs after widespread use of a drug to animal subjects. The aforesaid procedure of deriving practice based on information from preapproval labeling may misrepresent or deprecate the incidence and prevalence of specific ADEs. In this study, we make the most of the recently disseminated ADE data by the FDA for animal drugs and devices used in animals to address this public and welfare concern. For this purpose, we implemented 5 different methods (Pearson distance, Spearman distance, cosine distance, Yule distance, and Euclidean distance) to determine the most efficient and robust approach to properly discover highly associated ADEs from the reported data and accurately exclude noise-induced reported events, while maintaining a high level of correlation precision. Our comparative analysis of ADEs based on an artificial intelligence (AI) approach for the 5 robust similarity methods revealed high ADE associations for 2 drugs used in dogs and cats. In addition, the described distance methods systematically analyzed and compared ADEs from the drug labeling sections with a specific emphasis on analyzing serious ADEs. Our finding showed that the cosine method significantly outperformed all the other methods by correctly detecting and validating ADEs based on the comparative similarity association analysis compared with ADEs reported by preapproval clinical trials, premarket testing, or postapproval complication experience of FDA-approved animal drugs.

Wildfire dramatically alters the hydrologic response of a watershed such that even modest rainstorms can produce hazardous debris flows. Relative to shallow landslides, the primary sources of material and dominant erosional processes that contribute to post-fire debris-flow initiation are poorly constrained. Improving our understanding of how and where material is eroded from a watershed during a post-fire debris-flow requires (1) precise measurements of topographic change to calculate volumetric measurements of erosion and deposition, and (2) the identification of relevant morphometrically defined process domains to spatially constrain these measurements of erosion and deposition. In this study, we combine the morphometric analysis of a steep, small (0.01 km 2 ) headwater drainage basin with measurements of topographic change using high-resolution (2.5 cm) multi-temporal terrestrial laser scanning data made before and after a post-fire debris flow. The results of the morphometric analysis are used to define four process domains: hillslope-divergent, hillslope-convergent, transitional, and channelized incision. We determine that hillslope-divergent and hillslope-convergent process domains represent the primary sources of material over the period of analysis in the study basin. From these results we conclude that raindrop-impact induced erosion, ravel, surface wash, and rilling are the primary erosional processes contributing to post-fire debris-flow initiation in the small, steep headwater basin. Further work is needed to determine (1) how these results vary with increasing drainage basin size, (2) how these data might scale upward for use with coarser resolution measurements of topography, and (3) how these results change with evolving sediment supply conditions and vegetation recovery.

Studies examining post-wildfire sediment transport have often focused on changes to individual landscape compartments (planar slopes, rills, gullies, channels, or alluvial fans) or have captured coarse-scale hydrologic and sediment transport events at the drainage basin scale. We advance the understanding of functional and structural connectivity by quantifying changes of the morphodynamics of and sediment transport along seven rill-gully threads (RGTs) after two low intensity rainstorms in a burned basin from the 2008 Gap fire near Goleta, CA, USA. TLS surveys conducted within two months of the initial fire and three days after the rainfall events provide point clouds for high-resolution digital terrain models (DTMs). DTM differencing techniques and morphological sediment budgets from the RGTs showed discontinuous sediment transport along the extent of these two landscape compartments immediately after the rainfall. Surface runoff was unable to remove dry ravel deposits within the RGTs and implied a high degree of structural disconnectivity there. Dry ravel and runoff erosion from the contributing areas to the RGTs indicated functional and structural connectivity at this scale of analysis. The results provide clear evidence that small amounts of rainfall and gravity-induced erosion are interacting at different scales within the recently burned watershed to produce structural and functional disconnectivity along the RGTs. While the current system was transport-limited during the analyzed event, higher magnitude rainstorms may produce enhanced connectivity, resulting in the ability of surface runoff to remove the stored sediments and perhaps produce debris flows.

Recombinant AAV vectors are produced by transient transfection of mammalian cells. The virus is usually purified from a combination of lysed cells and spent culture medium by HPLC. We have developed a quantitative, real-time PCR assay for quantifying encapsidated single-stranded viral DNA (i.e. DNA-containing virions) in cell lysates and the spent culture medium. This requires extensive DNaseI digestion to reduce the amount of AAV replicative DNA, as well as plasmid and cellular DNA, to negligible amounts. To demonstrate the utility of this assay, we produced recombinant AAV in HeLa cells and five different types of 293 cells. We used primers to the EGFP transgene to detect the production of a recombinant AAV. We assayed the cell lysates and media by both our quantitative PCR assay and a functional transduction assay. The quantitative PCR assay data correlated well with the transduction assay data. Because this assay only requires standard PCR primers and SYBR Green I dye to detect the amplification of the PCR template, it will readily adapt to any target DNA sequence within the recombinant AAV genome. The recombinant AAV vector does not need to express a reporter gene, such as EGFP or beta-galactosidase in order to assay the amount of virus produced.

Debris flows are a common event in mountainous environments. They often possess the greatest potential for destruction of property and loss of lives in these regions. Delimiting the spatial extent of potential damage from debris flows relies on detailed studies of the location of depositional zones. Current research indicates debris flow fans have two distinct depositional zones. However, the two zones were derived from studies containing detailed analyses of only a few fans. High resolution airborne laser swath mapping (ALSM) data is used to calculate profile curvature and surface gradient on 19 debris flow fans on the eastern side of Death Valley. The relationship between these parameters is assessed to 1) identify if debris flow fans are accurately represented by two depositional zones, and 2) to assess how these terrain parameters relate to one another at the individual fan scale. The results show at least three zones of deposition exist within the sampled fans. These zones do not hold consistent when individual fan morphometry is analyzed in conjunction with localized fan surface gradients. Fans with consistently shallower gradients exhibit numerous depositional zones with more subtle changes in profile curvature. Steeper gradient fans exhibit significantly fewer zones with more pronounced local changes in profile curvature. The surface complexity of debris flow fans is evident from these analyses and must be accounted for in any type of hazard studies related to these features.

We have developed a very simple protocol to transfect mammalian cells with linear polyethylenimine (PEI). Linear PEI has been used to transfect nucleic acids into a wide variety of mammalian cells both in cell culture and in vivo. Almost all of these reports have used commercially available preparations of PEI. Our linear PEI protocol is as efficient as commercial reagents in the transfection of HEK293 and HeLa cells, but at only a fraction of the cost. Our protocol should be useful for many different applications. It should be particularly useful for large-scale production of recombinant proteins and viruses requiring transfection of mammalian cells in large batches. We have used this protocol to produce recombinant AAV, which requires transfection of cells with three plasmids simultaneously. One plasmid contains the recombinant AAV genome. The second plasmid expresses the AAV rep and cap genes. The third plasmid expresses several adenovirus genes that are required for AAV replication. We have assessed production of a recombinant AAV that expresses GFP both by quantitative PCR and by transduction of HeLa cells.

Techniques for handling CAD data, and the development of a comprehensive programme for integrating engineering software tools, which are to share CAD data, remain open issues in CAD research. The importance of addressing database problems in such endeavours is well known. However, before problems can be solved they must be clearly defined, and a clear definition of the CAD database problem has yet to be provided. In fact, the CAD database literature bemoans the lack of even a comprehensive functional specification for CAD databases. In this paper, results of research into the problems of CAD databases are reported in the form of a twenty point functional specification for CAD databases.

INTRODUCTION MANY attempts have been made to predict the resistance of the egg shell to fracture on the basis of chemical and physical measurements of the whole egg or the shell. Most of the early literature in this regard has been reviewed by Tyler (1961). Since that time, the studies of Frank et al. (1964, 1965) indicated that the physical variables of shell thickness, specific gravity, percent shell and shell weight could not explain more than 60 percent of the variation in crushing strength and that none of the major chemical constituents of the shell were important contributors to shell strength. Frank et al. (1965) suggested that an increase in the proportion of variation capable of being explained by physical measurements, particularly geometrical relationships of the egg is necessary before chemical analysis can lead to reliable estimations of shell strength. Richards and Swanson (1965) found that shape index was independent …

A total of 165 birds were reared in a standard floor brooding pen and 175 birds were reared in a controlled environmental chamber for 3 weeks and then transferred to the floor pen. The birds were the male progeny of 15 sires, each mated to 2 dams. Birds in the chamber treatment were heavier than those of the floor treatment at 7 weeks of age. The majority of the variation in 7-week body weight of floor treated birds could be accounted for by variation in 1-week body weight and 1–3 week growth rate, while for chamber treated birds 1-week body weight and 3–7 week growth rate was more highly associated with the variation in 7-week body weight. Heritability estimates for 4, 5, 6, and 7-week body weight were higher for the chamber treated birds than the floor treated birds. Variation in the heritability estimates of 7-week body weight could be associated with those periods of growth that influenced 7-week body weight variation: 1–3 week growth rate (floor treatment) and 3–7 week growth rate (chamber treatment). The data suggested that stress can be incorporated into a selection program for improved body weight.

The paper discusses the selection of input signals to minimize a measure of system parameter estimation error from noisy measurements of control system outputs. The measure is taken to be the inverse of the trace of the information matrix which is shown to be a suitable measure for a class of asymptotically unbiased and efficient estimates. The paper gives a sufficient condition for the input sequences to maximize the smallest eigenvalue of the information matrix and to let it go to infinity asymptotically. The optimal input sequence is shown to be the eigenvector of a certain matrix. The implications of the class of input sequence developed in this paper on the convergence of the estimates are briefly indicated.

This paper establishes two concepts of identifiability for the unknown parameters of linear, constant, stable, discrete-time dynamic systems. Necessary and sufficient conditions are obtained for the system parameters to be identifiable in the deterministic sense (Theorems 1-2) and stochastically identifiable (Theorem 3). These conditions are shown to be significant in studying the asymptotic properties of maximum likelihood estimators (Corollary 3.1). Generalizations of these concepts to include the identification of the system's initial state are also discussed (Theorems 2a and 3a).