Quantitative risk assessment of listeriosis due to consumption of raw milk

The objectives of this study were to estimate the risk of illness for raw milk consumers due to Listeria monocytogenes in raw milk sold by permitted dealers, and the risk for people on farms who consume raw milk. Three scenarios were evaluated for raw milk sold by dealers: raw milk purchased directly from bulk tanks, from on-farm stores, and from retail. To assess the effect of mandatory testing of raw milk by regulatory agencies, the number of listeriosis cases per year was compared where no raw milk testing was done, only a screening test to issue a permit was conducted, and routine testing was conducted and milk was recalled if it was L. monocytogenes positive. The median number of listeriosis cases associated with consumption of raw milk from bulk tanks, farm stores, and retail for an intermediate-age population was 6.6 × 10(-7), 3.8 × 10(-5), and 5.1 × 10(-5) cases per year, respective ly. In populations with high susceptibility, the estimated median number of cases per year was 2.7 × 10(-7) (perinatal, i.e., pregnant women and their fetuses or newborns) and 1.4 × 10(-6) (elderly) for milk purchased from bulk tanks, 1.5 × 10(-5 ) (perinatal) and 7.8 × 10(-5) (elderly) for milk from farm stores, and 2.1 × 10(-5) (perinatal) and 1.0 × 10(-4) (elderly) for milk from retail. For raw milk consumed on farms, the median number of listeriosis cases was 1.4 × 10(-7) cases per year. A greater risk of listeriosis was associated with consumption of raw milk obtained from retail and farm stores as compared with milk obtained from bulk tanks. This was likely due to additional time-temperature combination steps in the retail and farm store models, which increased the chances for growth of L. monocytogenes in raw milk. A close relationship between prevalence of L. monocytogenes in raw milk and the values of disease incidence was observed. Hence, a reduction in the number of cases per year in all populations was observed when a raw milk-testing program was in place, especially when routine testing and recalling of milk was conducted.     

Transduction of envelope stress in Escherichia coli by the Cpx two-component system

Disruption of normal protein trafficking in the Escherichia coli cell envelope (inner membrane, periplasm, outer membrane) can activate two parallel, but distinct, signal transduction pathways. This activation stimulates the expression of a number of genes whose products function to fold or degrade the mislocalized proteins. One of these signal transduction pathways is a two-component regulatory system comprised of the histidine kinase CpxA and the response regulator, CpxR. In this study we characterized gain-of-function Cpx* mutants in order to learn more about Cpx signal transduction. Sequencing demonstrated that the cpx* mutations cluster in either the periplasmic, the transmembrane, or the H-box domain of CpxA. Intriguingly, most of the periplasmic cpx* gain-of-function mutations cluster in the central region of this domain, and one encodes a deletion of 32 amino acids. Strains harboring these mutations are rendered insensitive to a normally activating signal. In vivo and in vitro characterization of maltose-binding-protein fusions between the wild-type CpxA and a representative cpx* mutant, CpxA101, showed that the mutant CpxA is altered in phosphotransfer reactions with CpxR. Specifically, while both CpxA and CpxA101 function as autokinases and CpxR kinases, CpxA101 is devoid of a CpxR-P phosphatase activity normally present in the wild-type protein. Taken together, the data support a model for Cpx-mediated signal transduction in which the kinase/phosphatase ratio is elevated by stress. Further, the sequence and phenotypes of periplasmic cpx* mutations suggest that interactions with a periplasmic signaling molecule may normally dictate a decreased kinase/phosphatase ratio under nonstress conditions.     

Mastitis and the shape of the lactation curve in Norwegian dairy cows

An investigation of the shape of the lactation curve and the mastitis incidence was conducted to identify whether management interventions of the lactation curve constitute a potential for reducing incidence of mastitis at herd level. Lactation curves were estimated to describe the variation of daily milk yield during the 305-d lactation period in Norwegian Red cows. Associations between mastitis incidence at herd level and lactation curve characteristics such as production level at onset of lactation, magnitude and time of peak milk yield, and increase and decrease of milk yield rates were studied. Data from 250,303 lactations occurring during 2005 and 2006 from 14,766 herds were obtained from the Norwegian Dairy Herd Recording System. Besides veterinary treatments, the records included information on monthly test-day milk yields. The shapes of the lactation curves at herd level were parameterized using a modified Wilmink model in two separate mixed model analyses. In the first analysis a subset of lactations with no records of veterinary treatments was used. Lactation curves from herds with high (>0·31 cases/305-d lactation) and low (<0·07 cases/305-d lactation) herd mastitis incidence rate were parameterized and compared for three separate strata of parity. The result showed that high herd mastitis incidence rate was associated with a low intercept (P<0·05), a steep slope before peak milk yield (P<0·01) and a rapid decline after peak milk yield (P<0·01). In the second analysis a subset of high-yielding lactations with veterinary treatments of mastitis only and lactations with no records of veterinary treatment were compared. This was done to investigate whether the findings at herd level were also reflected at cow level. These results showed that lactation curves from lactations with mastitis cases were associated with a steep slope before peak milk yield (P<0·05) in second and later parities and a rapid decline after peak milk yield (P<0·01) in all three parity groups.     

Irreversible conversion of xanthine dehydrogenase into xanthine oxidase by a mitochondrial protease

Irreversible conversion of xanthine dehydrogenase (XDH) to its oxygen free radical producing oxidase (XO) form occurs through an uncharacterized proteolytic process, which was studied in human liver. Upon incubation of fresh unfrozen liver cytosol, XDH remained intact. When recombinant human XDH was coincubated with subcellular fractions of human liver, the mitochondrial intermembrane space was shown to contain a heat-labile activity that converted XDH irreversibly to XO. This activity is resistant to inhibitors of all major groups of proteases. We postulate that this novel type of proteolytic enzyme is released into the cytosol upon mitochondrial damage.     

VIATO-visual interactive aircraft trajectory optimization

An approach toward the automated solution of aircraft trajectory optimization problems is introduced and implemented in an interactive program called visual interactive aircraft trajectory optimization (VIATO). This MS Windows-compatible software produces minimum time trajectories to a fixed or moving target. It is easy to use by nonexperts as no previous knowledge of the methods of optimal control theory or mathematical modeling are needed. VIATO consists of a graphical user interface, an optimization server, and a model server. In VIATO, different aircraft types are represented by a set of parameters. The equations of motion and state as well as control constraints are fixed in advance. Since the objective function is also specified, the user avoids the modeling and explicit formulation of optimal control problems. Reliable convergence to an approximate optimal solution is achieved by converting the original optimal control problem into a finite dimensional optimization problem. The parameterized problem is solved using nonlinear programming     

Prevalence, distribution, and diversity of Listeria monocytogenes in retail environments, focusing on small establishments and establishments with a history of failed inspections

Despite growing concerns about cross-contamination of ready-to-eat foods with Listeria monocytogenes, our knowledge about the ecology and transmission of L. monocytogenes in retail establishments has remained limited. We conducted a cross-sectional study to characterize the prevalence, distribution, and subtype diversity of L. monocytogenes in 120 New York State retail deli establishments that were hypothesized to present an increased risk for environmental L. monocytogenes contamination (i.e., small establishments and establishments with a history of failed New York State Agriculture and Markets inspections). Analysis of these data along with previously reported data for 121 predominantly larger retail establishments in New York State identified establishment size, geographic location, and inspection history as significant predictors of L. monocytogenes presence and prevalence. The odds of an establishment being L. monocytogenes positive were approximately twice as high for large establishments, establishments located in New York City, or establishments with poor inspection history (as compared with establishments without these attributes), even though correlation between location and inspection history complicated interpretation of results. Within an establishment, L. monocytogenes was significantly more prevalent on nonfood contact surfaces than on food contact surfaces; prevalence was particularly high for floors and in floor drains, sinks, the dairy case, and milk crates. L. monocytogenes subtype diversity differed between sites, with lineage I isolates significantly associated with nonfood contact surfaces and lineage II isolates significantly associated with food contact surfaces. Isolates belonging to the same ribotype were often found dispersed across multiple sites within an operation.     

Antioxidant enzyme regulation and resistance to oxidants of human bronchial epithelial cells cultured under hyperoxic conditions

OBJECTIVE: The measurement of total serum testosterone has an established clinical role in the management of male hypogonadism and female androgen excess disorders. We studied the between-kit variability and precision of six different commercially available testosterone assays and compared them with an established in-house method. DESIGN: Laboratory observational prospective study. SETTING: Tertiary university medical center clinical laboratory. PATIENT(S): Three groups of samples each of men (n = 36) and women (n = 15) who had high, normal, or low levels of sex hormone-binding globulin (SHBG), respectively, were studied. INTERVENTION(S): Individual and pooled (male and female) serum samples were analyzed for total testosterone concentration using six different commercially available assays and one in-house method. MAIN OUTCOME MEASURE(S): The between-kit variability and the effect of the mean (+/- SD) SHBG level were determined, the results obtained with the use of the kits and the in-house method were compared, and the intraassay variability (i.e., precision) was evaluated. RESULT(S): Male samples demonstrated a 26.3%-40.8% variance in the results obtained with different kits, which was greatest for samples with the lowest SHBG levels. For female samples, between-kit variability ranged from 57%-115% (average, 77%). The percent deviation of the results obtained with the use of commercial methods from those obtained with the use of our in-house assay was greater for men (mean variance, 194%) than for women (mean variance, 67%). The female pool intraassay coefficient of variation was 3.8% with the use of the in-house method and ranged from 8.9%-21.2% with the use of the commercial kits. The male pool intraassay coefficient of variation was 3.1% with the use of the in-house method and ranged from 3.3%-5.5% with the use of the commercial kits. CONCLUSION(S): Most commercially available kits for measuring the total serum testosterone level demonstrated significant between-kit variability, which was greatest for female samples. Further, samples with the lowest SHBG levels had the highest between-kit variances. These data strongly suggest that the measurement of total serum testosterone using commercial kits may have limited utility, particularly for the detection of hyperandrogenemia.     

An agent-based model evaluation of economic control strategies for paratuberculosis in a dairy herd

This paper uses an agent-based simulation model to estimate the costs associated with Mycobacterium avium ssp. paratuberculosis (MAP), or Johne's disease, in a milking herd, and to determine the net benefits of implementing various control strategies. The net present value (NPV) of a 1,000-cow milking herd is calculated over 20 yr, parametrized to a representative US commercial herd. The revenues of the herd are generated from sales of milk and culled animals. The costs include all variable and fixed costs necessary to operate a representative 1,000-cow milking herd. We estimate the NPV of the herd with no MAP infection, under an expected endemic infection distribution with no controls, and under an expected endemic infection distribution with various controls. The initial number of cows in a herd with an endemic MAP infection is distributed as 75% susceptible, 13% latent, 9% low MAP shedding, and 3% high MAP shedding. Control strategies include testing using ELISA and fecal culture tests and culling of cows that test positive, and culling based on observable milk production decrease. Results show that culling cows based on test results does not increase the herd's NPV and in most cases decreases NPV due to test costs as well as false positives and negatives with their associated costs (e.g., culling healthy cows and keeping infected cows). Culling consistently low producing cows when MAP is believed to be present in the herd produces higher NPV over the strategy of testing and culling MAP infected animals, and over the case of no MAP control.     

Expression and developmental profile of antioxidant enzymes in human lung and liver

Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 micrograms. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.