SDG indicator 3.b.3 - an analysis of its robustness and challenges for measuring access to medicines for children.

BACKGROUND: Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines' accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. METHODS: Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. RESULTS: The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0-58.8%) and 76.3% (range 57.2-90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. CONCLUSION: This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Risk associated with transportation and lairage on hide contamination with Salmonella enterica in finished beef cattle at slaughter.

Transportation of cattle to the slaughter plant could influence hide contamination with Salmonella enterica. Fecal and hide samples were obtained from 40 lots of cattle at the feedlot and again at the slaughter plant. Potential risk factors for hide contamination were evaluated. A multilevel Poisson regression model was used to determine whether transportation and lairage were associated with hide contamination by Salmonella. Cattle with hide samples positive for Salmonella at the feedlot had twice the risk of having positive slaughter hide samples compared with cattle without positive feedlot hide samples (relative risk [RR], 1.9). Cattle transported in trailers from which samples positive for Salmonella were collected had twice the risk of having positive slaughter hide samples compared with cattle transported in culture-negative trailers (RR, 2.3). Cattle transported for long distances had twice the risk of having positive hide samples at slaughter compared with cattle transported shorter distances (RR, 2.3). Cattle held in lairage pens contaminated with feces had twice the risk of having positive slaughter hide samples compared with cattle held in clean pens (RR, 1.8). Cattle held off feed longer than 18 h before loading had twice the risk of having positive slaughter hide samples compared with cattle held off feed for shorter times (RR, 1.7). Cattle that were agitated during loading had twice the risk of having positive slaughter hide samples compared with cattle that were calm (RR, 2.2). These findings suggest that variables associated with transportation and lairage can impact the presence of Salmonella on the hides of cattle at slaughter.

Impact of transportation and lairage on hide contamination with Escherichia coli O157 in finished beef cattle.

Transportation of cattle from the feedlot to the slaughter plant could influence hide contamination of Escherichia coli O157. A study was initiated to investigate the influence of transportation and lairage on shedding and hide contamination of E. coli O157. Fecal and hide samples were obtained from 40 pens of harvest-ready beef cattle at the feedlot prior to transport and again at the slaughter plant immediately after slaughter. Potential risk factors for hide contamination at the feedlot, during transport, and at slaughter were evaluated. A multilevel Poisson regression model was used to evaluate if transportation and lairage were associated with hide contamination by E. coli O157 in finished beef cattle. Lots of cattle held in E. coli O157-positive lairage pens had eight times greater risk of having positive slaughter hide samples compared with cattle held in culture-negative pens (relative risk, 8.0; 95% confidence interval, 1.6 to 38.8). Lots of cattle that were held in lairage pens contaminated with feces had three times greater risk for positive slaughter hide samples compared with cattle held in clean pens (relative risk, 3.1; 95% confidence interval, 1.2 to 7.9). Lots of cattle that were transported for long distances (> 160.9 km) had twice the risk of having positive hide samples at slaughter compared with cattle transported a shorter distance (relative risk, 2.4; 95% confidence interval, 1.1 to 5.1). These findings suggest that transportation and lairage should be considered in E. coli O157 control strategies.

Evaluation of factors associated with increased dairy cow mortality on United States dairy operations.

Dairy cow mortality is an increasingly severe problem for the US dairy industry. The objective of this study was to examine a variety of herd management practices and herd characteristics to identify factors associated with increased cow mortality in US dairy herds. The National Animal Health Monitoring System's Dairy 2002 study surveyed dairy operations in 21 major dairy states. The complete data set included results from 953 dairy farms with a minimum of 30 dairy cows per farm. Associations between dairy cow mortality and 119 a priori-selected management practices or characteristics of 953 operations were evaluated. Eighty of the 119 risk factors explored in a univariate analysis met initial inclusion criteria for further evaluation of association with dairy cow mortality. A multivariable analysis was conducted to explore more complex relationships. The final multivariable model included 7 representative variables: herd levels of respiratory disease, lameness, and antibiotic use for treating sick cows, the percentage of culled cows less than 50 d in milk, the average calving interval, the use of a total mixed ration, and the region of the country. Increased odds of a greater level of mortality on farms was associated with greater percentages of lameness, respiratory disease, and sick cows treated with antibiotics, demonstrating the influence of physical derangements and disease on dairy cow mortality. Increased odds of a greater level of mortality was also associated with feeding a total mixed ration, culling fewer cows in early lactation, and herds located in western, midwestern, and southeastern regions relative to the northeastern United States, pointing to the importance of management decisions and operation characteristics on mortality outcomes. Further, an important interplay between facets of health and management on dairy cow mortality was suggested through the inclusion of the calving interval, with a longer calving interval leading to increased odds of a greater level of mortality on farms. Analysis of a variety of herd characteristics and practices with nationally representative data suggests that several health problems in tandem with aspects of operational construct and management are associated with increasing mortality.

Factors associated with occurrence and recovery of nonambulatory dairy cows in the United States.

The primary objective of this study was to compare characteristics of US dairy operations that had one or more nonambulatory cows (unable to rise for any period of time) (cases) with operations that had no nonambulatory cows (controls) during 2004. A secondary objective was to describe factors associated with recovery of the last nonambulatory cow on the operation during 2004. Case dairy operations (n = 1,822) more often fed a total mixed ration [odds ratio (OR) = 2.0; confidence interval (CI): 1.1-3.4], produced more than 9,090 kg of milk (OR = 2.8; CI: 1.8-4.5), and were more likely to be of medium to large herd size (100 or more head of adult cows, OR = 3.7; CI: 2.2-6.2) compared with control dairies (n = 151). Compared with operations where the predominant flooring surface on which lactating cows stood or walked in winter was pasture, operations where pasture was not the predominant surface were at increased risk of having nonambulatory cows (OR = 4.7; CI: 2.2-10.2). Cows nonambulatory for less than 24 h were more likely to recover compared with cows nonambulatory for 24 h or more (OR = 3.0; CI: 2.0-4.4). Cows that received calcium, phosphorus, or potassium while non-ambulatory were more likely to recover (OR = 3.6; CI: 2.1-6.1) than cattle that did not receive these treatments. Cattle that were not repositioned periodically were more likely to recover (OR = 2.1; CI: 1.4-3.1), as were cattle that were not treated by a veterinarian before becoming nonambulatory (OR = 1.9; CI: 1.1-3.3). These findings are consistent with prolonged recumbency and prior history of health issues, respectively. Nonambulatory cattle with hypocalcemia were more likely to recover (OR = 6.0; CI: 3.4-10.7) compared with nonambulatory cows with all other causes of a nonambulatory condition (analyzed collectively as a single variable but including cancer, clinical mastitis, digestive conditions, metabolic imbalances, neurological problems, respiratory disease, other, unknown). The results of this study reveal that the majority of US dairy operations have at least one nonambulatory dairy cow over the course of a year. Additionally, individual animal factors associated with being nonambulatory may lead to improved identification and treatment of animals that are nonambulatory for a prolonged period. From the perspective of recovery, considering euthanasia is appropriate for cows that have been nonambulatory for more than 24 h.

Risk factors for owner-reported occurrence of equine protozoal myeloencephalitis in the US equine population.

BACKGROUND: Equine protozoal myeloencephalitis (EPM) is a serious and often fatal neurologic disease of horses, but few studies have investigated risk factors. OBJECTIVES: To evaluate operation- and individual-level factors associated with likelihood of the occurrence of EPM. ANIMALS: Data were collected as part of a study of the US equine industry from 1,178 operations representing 83.9% of horses and 51.6% of operations with > or =3 horses in 28 states. METHODS: Probability-based sampling was used to enroll representative operations in a cross-sectional study. Interviews were conducted to collect information regarding health and management of horses. A nested case-control study was used to investigate risk factors among individual horses. Interview data were combined with climate data, human population density, and opossum regional ecology categories. Data were analyzed using logistic regression to identify risk factors for the occurrence of EPM. RESULTS: Owners reported that 95% of EPM cases included in this study were diagnosed by veterinarians. Variables associated with EPM occurrence on premises included opossum regional ecology, reported exposure to small wildlife, climate, terrain, housing, choice of bedding material, method of storing feeds, equine stocking density, and primary use of horses. Among individual horses, age was most strongly associated with disease risk. Associations also were identified with sex, breed, primary use, and participation in competitions. CONCLUSIONS AND CLINICAL IMPORTANCE: Because the risk of EPM occurrence on operations is closely tied to factors that impact exposure to opossums, their feces, and their environment, controlling these exposures may be important in preventing the occurrence of EPM.

Herd management practices and their association with bulk tank somatic cell count on United States dairy operations.

The objective of this study was to evaluate associations between bulk tank somatic cell count (BTSCC) and herd management practices using data collected in the National Animal Health Monitoring System Dairy 2002 study. Twenty-six percent and 17.8% of 1,013 operations reported a BTSCC < 200,000 cells/mL and > 400,000 cells/mL, respectively. Univariate analysis identified associations between management variables and BTSCC. The use of mattresses, sand, and newspaper as bedding were all associated with a lower BTSCC. Primary lactating cow housing facility, outside maternity housing area, flooring type cows walk or stand on, and use of automatic take-offs were also associated with BTSCC. Multivariate associations between management variables and BTSCC were determined by backward elimination ordinal logistic regression. The odds of an operation from the West, Midwest, and Northeast having a high BTSCC were lower than those from the Southeast. The odds of a higher BTSCC were 2 times greater for operations with a rolling herd average milk production < 9,090 kg/cow per year compared with those with > or = 9,090 kg/cow per year. Operations using composted manure were 2.9 times more likely to have a higher BTSCC than those not using composted manure. Finally, operations that reported not using a coliform mastitis vaccine were 1.7 times more likely to have a higher BTSCC than those using one. Future studies of the association between management practices and BTSCC should include an evaluation of the quality of management practice application and herd prevalence of contagious mastitis pathogens. Significant variables identified in this study dealt with housing, use of composted manure for bedding, and coliform mastitis vaccine use, suggesting the effect of environmental mastitis pathogens may be more influential on BTSCC than previously thought.

Evaluation of environmental sampling and culture to determine Mycobacterium avium subspecies paratuberculosis distribution and herd infection status on US dairy operations.

The objectives of this study were to determine the distribution of Mycobacterium avium subspecies paratuberculosis (MAP) in the environment and assess the relationship between the culture status of MAP in the farm environment and herd infection status. The National Animal Health Monitoring System's Dairy 2002 study surveyed dairy operations in 21 states. One component of the study involved collection and culturing of environmental samples for MAP from areas on farms where manure accumulated from a majority of a herd's cows. Operations were selected for inclusion based on perceived risk factors for MAP infection identified in a previously administered questionnaire. Individual animal and environmental samples were collected and used to determine the efficiency of environmental sampling for determination of herd infection status. Individual animal fecal, serum, and milk samples were used to classify herds as infected or not infected based on the presence of at least one test-positive animal in the herd. A total of 483 environmental samples (approximately 5 per farm) were collected, and 218 (45.1%) were culture-positive for MAP. A similar percentage of environmental cultures collected from all designated areas were positive [parlor exits (52.3%), floors of holding pens (49.1%), common alleyways (48.8%), lagoons (47.4%), manure spreaders (42.3%), and manure pits (41.5%)]. Of the 98 operations tested with the environmental sample culture, 97 had individual serum ELISA results, 60 had individual fecal culture results, and 34 had individual milk ELISA results. Sixty-nine of the 98 operations (70.4%) had at least one environmental sample that was culture-positive. Of the 50 herds classified as infected by fecal culture, 38 (76.0%) were identified by environmental culture. Two of the 10 operations classified as not infected based on individual animal fecal culture were environmental culture-positive. Of the 80 operations classified as infected based on serum ELISA-positive results, 61 (76.3%) were identified as environmental-positive, whereas 20 of the 28 (71.4%) operations identified as infected based on milk ELISA were detected by environmental sampling. Environmental sample culturing is less costly than individual animal sampling, does not require animal restraint, and identified more than 70% of infected operations. Environmental sampling is another diagnostic tool that veterinarians and dairy producers can use to determine herd infection status for MAP.

Increased generation of lipid-derived and ascorbate free radicals by L1210 cells exposed to the ether lipid edelfosine.

Using the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected a lipid-derived carbon-centered free radical generated from intact L1210 lymphoblastic leukemia cells that were exposed to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (edelfosine or ET-18-OCH3) and oxidative stress. The spectral characteristics, including hyperfine splitting constants of aN = 15.61G and aH = 2.65G, were consistent with the spin trapping of an alkyl radical. Radical detection required iron and prior enrichment of cellular components with the polyunsaturated fatty acid docosahexaenoic acid; unmodified cells failed to generate detectable free radical. Ascorbate further enhanced radical generation. The detection of lipid-derived free radicals when intact cells are exposed to edelfosine provides further evidence that oxidative stress may play an important role in the cytotoxic mechanism of this class of anticancer drug.

Membrane peroxidative damage enhancement by the ether lipid class of antineoplastic agents.

The ether lipid antineoplastic agents have no known interaction with DNA, but rather they appear to target membranes. The primary mechanism of action is unknown but effects on membrane biology are documented. We have studied the effect of two ether lipids on membrane lipids and examined the hypothesis that membrane peroxidative damage may be involved in their mechanism of action. With the use of cells having membranes enriched in polyunsaturated fatty acids of the omega-3 family of fatty acids, we have demonstrated that the prototypical ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and a thioether lipid analogue, 1-O-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine , increase membrane lipid peroxidation and cytotoxicity in a time- and drug concentration-dependent manner. The oxidative cofactors Fe2+ and ascorbic acid were required. The pattern of cell death did not fully correspond to the peroxidation, since cofactors were required for peroxidation but not cytotoxicity. However, the rate of decrease in cell viability after exposure to the drug and cofactors corresponded to the peroxidation rate. In addition, when L1210 cells modified with the monounsaturated fatty acid oleic acid or unmodified cells were used, there was no ether lipid-enhanced peroxidation, and the cells were significantly less sensitive to the drug, with or without cofactors. The lipid-soluble antioxidant vitamin E inhibited 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine peroxidation and cytotoxicity in a concentration-dependent manner in the presence of cofactors but not consistently without them. Depletion of cellular glutathione content of L1210 cells using L-buthionine-(SR)-sulfoximine resulted in 40% augmentation of cofactor-facilitated cytotoxicity of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and a borderline effect on peroxidation. Another ether lipid, the thio compound 1-O-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine , enhanced peroxidation in the presence of cofactors with kinetics corresponding to those of cytotoxicity. In the presence of ether lipid and cofactors the intensity of ascorbate free radical increased, consistent with oxidative stress. We conclude that the ether lipids stimulate membrane lipid peroxidation in a time- and drug concentration-dependent manner in the presence of oxidative cofactors. Even though peroxidation may not fully explain the cytotoxic effect of the ether lipid class of anticancer drugs, this observation provides further information on the nature of the membrane damage induced by the drugs. Since the ether lipids generate no known free radical intermediates directly, this suggests that membrane damage indirectly results in a process involving a peroxidative reaction.

Sensitivity of K562 and HL-60 cells to edelfosine, an ether lipid drug, correlates with production of reactive oxygen species.

Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine; ET-18-OCH3), a membrane-targeting anticancer ether lipid drug has been shown previously in vitro to be capable of initiating oxidative processes in cells. Here we study two human leukemia cell lines (HL-60 and K562) that have different sensitivities to edelfosine; HL-60 cells are more sensitive than K562 cells. To determine whether edelfosine alters the sensitivity of these lines to an oxidative stress, cells were subjected to the oxidative stress of iron(II) plus ascorbate and then monitored for free radical formation, membrane integrity, and cytotoxicity. The HL-60 cell was sensitive to the ether lipid drug in clonogenic and dye exclusion assays; a lipid-derived free radical was generated by this sensitive cell in the presence of small amounts of Fe2+ and ascorbate as detected by electron paramagnetic resonance and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. There was also simultaneous generation of an ascorbate-free radical, which has been shown to estimate cellular oxidative flux. In contrast, the K562 cell was resistant to edelfosine cytotoxicity in all assays and did not generate either lipid-derived or ascorbate-free radicals. Subcellular homogenates of the HL-60 cell generated both radicals when exposed to the drug, but homogenates of K562 did not generate either, suggesting that differential drug uptake or intracellular drug localization is not the cause of the difference in oxidation. Trypan blue uptake by the HL-60, but not the K562 cells, measured under the same conditions as the oxidation experiments, demonstrated a loss of membrane impermeability with similar time and concentration dependence, suggesting a causal relationship of membrane damage and radical generation. Complementary studies of HL-60 cell membrane integrity with propidium iodide impermeability and light scatter using the flow cytometer showed a concentration dependence that was similar to radical generation. Biochemical studies of the fatty acids of the HL-60 cell revealed more highly polyunsaturated lipids in the cells. Cellular antioxidant enzymes and vitamin E contents of the two cell lines were similar. We conclude that there is a time- and concentration-dependent generation of important oxidations by the sensitive HL-60 cells exposed to the membrane-targeted ether lipid, but the resistant K562 cells are oxidatively silent. This may be due in part to the differences in fatty acid polyunsaturation of the cellular membranes. The difference in oxidative susceptibility could be the basis for drug resistance to this membrane-specific anticancer agent.

Natural killer cells and their precursors in mice with severe combined immunodeficiency.

Our studies with scid mice have clarified the relationship between T cells and NK cells. C.B-17 scid mice have normal frequency of transplantable NK progenitors in their bone marrow which develop into fully functional NK cells. Spleens of scid mice contain mature NK cells which are phenotypically and functionally indistinguishable from NK cells found in normal mice. These cells retain their TCR genes in germline configuration and do not transcribe the CD3 genes. Thus, NK cells are distinct from the earliest identifiable cells committed to the T-lineage. In addition to the spleen, the thymus of scid mice also contains mature NK cells. These cells constitute a small proportion of the thymus cell population and can be clearly distinguished from the majority of cells, which have the phenotype and molecular characteristics of very early T-lineage cells. There is no evidence that NK cells within the thymus are derived in situ from a common NK/T precursor. Together these data support the hypothesis that NK cells form an independent lineage.

Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473.

The purpose of this study was to determine the maximum tolerated dose and dose-limiting toxicities of fish oil fatty acid capsules containing omega-3 fatty acid ethyl esters. Twenty-two patients with neoplastic disease not amenable to curative therapy who had lost 2% of body weight over a previous 1 month time period were given an escalating dose of fish oil fatty acids. The maximum tolerated dose was found to be 0.3 g/kg per day of this preparation. This means that a 70-kg patient can generally tolerate up to 21 1-g capsules/day containing 13.1 g of eicosapentaenoic acid + docosahexaenoic acid, the two major omega-3 fatty acids. Dose-limiting toxicity was gastrointestinal, mainly diarrhea, and a poorly described toxicity designated as "unable to tolerate in esophagus or stomach." A patient with chronic lymphocytic leukemia taking the fish oil provided an unusual opportunity to perform a detailed biochemical study of the effect of fish oil capsules on the lipids of malignant cells at several sequential time points in treatment. Studies of the malignant lymphocytes, serum, and whole blood of this one patient revealed an increase in eicosapentaenoic acid, the major component of the fish oil capsules, during fish oil capsule treatment. This study provides a scientific basis for the selection of omega-3 fatty acid doses for future studies in cancer. The maximum tolerated dose found is considerably higher than anticipated from published studies of many human diseases. The observation of a modification of the lipids of leukemic cells, serum, and blood in a patient with chronic leukemia provides a biochemical basis for a possible effect of fish oil supplements on cancer cachexia and tumor growth.

Effect of diagnostic testing error on intracluster correlation coefficient estimation.

Estimation of the intracluster correlation coefficient (ICC) for infectious animal diseases may be of interest for survey planning and for calculating variance inflation factors for estimators of prevalence. Typically, diagnostic tests with imperfect sensitivity and specificity are used in surveys. In such studies, where animals from multiple herds are tested, the ICC often is estimated using apparent (test-based) rather than true prevalence data. Through Monte Carlo simulation, we examined the effect of substituting diagnostic test outcomes for true infection status on an ANOVA estimator of ICC, which was designed for use with true infection status data. We considered effects of diagnostic test sensitivity and specificity on the estimated ICC when the true ICC value and infection status of the sampled individuals were known. The ANOVA estimator underestimated the true ICC when the diagnostic test was imperfect. We also demonstrated, under the beta-binomial model, that the ICC based on apparent infection status for individuals is < or = ICC based on true infection status. In addition, we propose a Bayesian model for estimating the ICC that incorporates imperfect sensitivity and specificity and illustrate the Bayesian model using a simulation study and one example; a seroprevalence survey of ovine progressive pneumonia in U.S. sheep flocks.

Comparison of mixed effects models of antimicrobial resistance metrics of livestock and poultry Salmonella isolates from a national monitoring system.

Antimicrobial use in agriculture is considered a pathway for the selection and dissemination of resistance determinants among animal and human populations. From 1997 through 2003 the U.S. National Antimicrobial Resistance Monitoring System (NARMS) tested clinical Salmonella isolates from multiple animal and environmental sources throughout the United States for resistance to panels of 16-19 antimicrobials. In this study we applied two mixed effects models, the generalized linear mixed model (GLMM) and accelerated failure time frailty (AFT-frailty) model, to susceptible/resistant and interval-censored minimum inhibitory concentration (MIC) metrics, respectively, from Salmonella enterica subspecies enterica serovar Typhimurium isolates from livestock and poultry. Objectives were to compare characteristics of the two models and to examine the effects of time, species, and multidrug resistance (MDR) on the resistance of isolates to individual antimicrobials, as revealed by the models. Fixed effects were year of sample collection, isolate source species and MDR indicators; laboratory study site was included as a random effect. MDR indicators were significant for every antimicrobial and were dominant effects in multivariable models. Temporal trends and source species influences varied by antimicrobial. In GLMMs, the intra-class correlation coefficient ranged up to 0.8, indicating that the proportion of variance accounted for by laboratory study site could be high. AFT models tended to be more sensitive, detecting more curvilinear temporal trends and species differences; however, high levels of left- or right-censoring made some models unstable and results uninterpretable. Results from GLMMs may be biased by cutoff criteria used to collapse MIC data into binary categories, and may miss signaling important trends or shifts if the series of antibiotic dilutions tested does not span a resistance threshold. Our findings demonstrate the challenges of measuring the AMR ecosystem and the complexity of interacting factors, and have implications for future monitoring. We include suggestions for future data collection and analyses, including alternative modeling approaches.

Effects of exogenous lipids on cancer and cancer chemotherapy. Implications for treatment.

The addition of fatty acids to the diets of tumour-bearing animals results in specific and defined structural modification of the tumour membrane lipids without disrupting the cell. Furthermore, fatty acids at higher concentrations may act directly as anticancer agents, and there is evidence of selective sensitivity of neoplastic cells. Similarly, experimental enrichment of the diets with specific lipids modulates carcinogen-induced tumorigenesis at the initiation or promotion steps, and in some animal models, the growth rate of established tumours. Therefore, anticancer therapies which utilise lipid-based strategies may be useful clinically. Although dietary strategies used alone may have some favourable effect, it seems likely that the combination of diet with anticancer drugs has the best possibility of providing the extent of cytotoxicity required for tumour eradication. Such combinations could take advantage of an additive effect of each, or could act synergistically such as by the influence of dietary fatty acid modification on drug transport. However, dietary lipids may also increase the toxicity of anticancer drugs to normal tissues and decrease the therapeutic index. Further research is needed to define the role of lipids in future chemotherapy.

Seasonal values of selected blood parameters of farm-raised channel catfish (Ictalurus punctatus) in the Mississippi Delta.

Hematocrit, sodium, chloride, potassium, calcium, glucose, and pH were measured in whole blood of 1,522 channel catfish collected from 3 commercial food-fish ponds in the Mississippi Delta. Samples were collected from March 1995 to March 1996 to monitor seasonal fluctuations. A total of 10-20 fish were arbitrarily collected with snag lines from each pond on each sample day. The mean monthly hematocrits fluctuated seasonally from a low of 14.5% in midwinter to a high of 25.7% in midsummer (annual x = 21%, SE = 0.15). Sodium levels were consistent throughout the year with a mean (SE) of 134 (0.13) mM/liter. Mean chloride values for the year were 120 (0.14) mM/liter but increased to 132 mM/liter in midwinter. By March 1996, the chloride levels had returned to levels observed during spring 1995. Potassium and glucose levels varied throughout the year with means of 4.43 (0.06) mM/liter and 26.9 (0.46) mg/dl, respectively, and coefficients of variation of 51.8% and 63.3%, respectively. Calcium and pH values were fairly stable with means of 1.31 (0.004) mM/liter and 7.13 (0.004), respectively. All parameters except glucose and potassium may be adequately evaluated with a sample size of 25 or less. These data were collected to provide baseline information for ongoing pond health studies.

Herd-level economic losses associated with Johne's disease on US dairy operations.

Johne's disease ('paratuberculosis') is a chronic, infectious, wasting disease that affects dairy cattle. Estimation of its impact on herd productivity and corresponding economic loss on US dairy operations was part of the USDA National Animal Health Monitoring System's (NAHMS) 1996 national dairy study. Johne's-positive herds experience an economic loss of almost US$ 100 per cow when compared to Johne's-negative herds due to reduced milk production and increased cow-replacement costs. For Johne's-positive herds that reported at least 10% of their cull cows as having clinical signs consistent with Johne's disease, economic losses were over US$ 200 per cow. These high-prevalence herds experienced reduced milk production of over 700 kg per cow, culled more cows but had lower cull-cow revenues, and had greater cow mortality than Johne's-negative herds. Averaged across all herds, Johne's disease costs the US dairy industry, in reduced productivity, US$ 22 to US$ 27 per cow or US$ 200 to US$ 250 million annually.

Papillomatous digital dermatitis and associated risk factors in US dairy herds.

The objective of this study was to describe the incidence of papillomatous digital dermatitis in the US (including regional and herd size patterns) and to evaluate specific herd-level management factors associated with high incidence of digital dermatitis in US dairy herds. The study design was a population-based cross-sectional survey. US dairy operations with at least 30 cows in 20 states, representing 79% of US dairy cows, were sampled. On participant operations, a questionnaire was administered by veterinary medical officer or animal-health technicians on-farm to dairy managers. Papillomatous digital dermatitis was reported in milk cows in the previous 12 months from 43.5% of US dairy herds. Seventy-eight percent of affected herds reported that their first cases occurred in 1993 or later. Regions of the USA with the highest percent of herds affected included the Southwest, Northwest, and Northeast. Factors associated with high (> 5%) incidence of papillomatous digital dermatitis included region, herd size, type of land lactating cows accessed on a daily basis, flooring type where lactating cows walked, percent of cows born off the operation, use of a primary hoof trimmer who trimmed cows' hooves on other operations, and lack of washing of hoof-trimming equipment between cows. Papillomatous digital dermatitis has been recently reported from dairy herds across the US. This study suggests that a high percentage of herds with digital dermatitis could be prevented. Management strategies to potentially prevent or reduce incidence of digital dermatitis on dairy operations include those related to biosecurity and 'cow hoof' environmental conditions.