Evaluation of 4 predictive algorithms for intramammary infection status in late-lactation cows.

The objective of this observational study was to compare 4 cow-level algorithms to predict cow-level intramammary infection (IMI) status (culture and MALDI-TOF) in late-lactation US dairy cows using standard measures of test performance. Secondary objectives were to estimate the likely effect of each algorithm, if used to guide selective dry cow therapy (SDCT), on dry cow antibiotic use in US dairy herds, and to investigate the importance of including clinical mastitis criteria in algorithm-guided SDCT. Cows (n = 1,594) from 56 US dairy herds were recruited as part of a previously published cross-sectional study of bedding management and IMI in late-lactation cows. Each herd was visited twice for sampling. At each farm visit, aseptic quarter-milk samples were collected from 20 cows approaching dry-off (>180 d pregnant), which were cultured using standard bacteriological methods and MALDI-TOF for identification of isolates. Quarter-level culture results were used to establish cow-level IMI status, which was considered the reference test in this study. Clinical mastitis records and Dairy Herd Improvement Association test-day somatic cell count data were extracted from herd records and used to perform cow-level risk assessments (low vs. high risk) using 4 algorithms that have been proposed for SDCT in New Zealand, the Netherlands, United Kingdom, and the United States. Agreement between aerobic culture (reference test; IMI vs. no-IMI) and algorithm status (high vs. low risk) was described using Cohen's kappa, test sensitivity, specificity, negative predictive value, and positive predictive value. The proportion of cows classified as high risk among the 4 algorithms ranged from 0.31 to 0.63, indicating that these approaches to SDCT could reduce antibiotic use at dry-off by 37 to 69% in the average US herd. All algorithms had poor agreement with IMI status, with kappa values ranging from 0.05 to 0.13. Sensitivity varied by pathogen, with higher values observed when detecting IMI caused by Streptococcus uberis, Streptococcus dysgalactiae, Staphylococcus aureus, and Lactococcus lactis. Negative predictive values were high for major pathogens among all algorithms (≥0.87), which may explain why algorithm-guided SDCT programs have been successfully implemented in field trials, despite poor agreement with overall IMI status. Removal of clinical mastitis criteria for each algorithm had little effect on the algorithm classification of cows, indicating that algorithms based on SCC alone may have similar performance to those based on SCC and clinical mastitis criteria. We recommend that producers implementing algorithm-guided SDCT use algorithm criteria that matches their relative aspirations for reducing antibiotic use (high specificity, positive predictive value) or minimizing untreated IMI at dry-off (high sensitivity, negative predictive value).

Partial budget analysis of culture- and algorithm-guided selective dry cow therapy.

The objectives of this study were to (1) use partial budget analysis to estimate the cash impact for herds that switch from blanket dry cow therapy (BDCT) to culture- or algorithm-guided selective dry cow therapy (SDCT) and (2) conduct a sensitivity analysis to investigate effects in situations where SDCT increased clinical and subclinical mastitis risk during the subsequent lactation. A partial budget model was created using Monte Carlo simulation with @Risk software. Expenditures associated with dry-off procedures and health outcomes (clinical and subclinical mastitis) during the first 30 d in milk were used to model herd-level effects, expressed in units of US dollars per cow dry-off. Values for each economic component were derived from findings from a recent multisite clinical trial, peer-reviewed journal articles, USDA databases, and our experiences in facilitating the implementation of SDCT on farms. Fixed values were used for variables expected to have minimal variation within the US dairy herd population (e.g., cost of rapid culture plates) and sampling distributions were used for variables that were hypothesized to vary enough to effect the herd net cash impact of one or more DCT approach(es). For Objective 1, herd-level udder health was assumed to be unaffected by the implementation of SDCT. For culture-guided SDCT, producers could expect to save an average of +$2.14 (-$2.31 to $7.23 for 5th and 95th percentiles) per cow dry-off as compared with BDCT, with 75.5% of iterations being ≥$0.00. For algorithm-guided SDCT, the mean net cash impact was +$7.85 ($3.39-12.90) per cow dry-off, with 100% of iterations being ≥$0.00. The major contributors to variance in cash impact for both SDCT approaches were percent of quarters treated at dry-off and the cost of dry cow antibiotics. For Objective 2, we repeated the partial budget model with the 30-d clinical and subclinical mastitis incidence increasing by 1, 2, and 5% (i.e., risk difference = 0.01, 0.02, and 0.05) in both SDCT groups compared with BDCT. For algorithm-guided SDCT, average net cash impacts were ≥$0.00 per cow dry-off (i.e., cost effective) when mastitis incidence increased slightly. However, as clinical mastitis incidence increased, economic returns for SDCT diminished. These findings indicate that when SDCT is implemented appropriately (i.e., no to little negative effect on health), it might be a cost-effective practice for US herds under a range of economic conditions.

Postcalving udder health and productivity in cows approaching dry-off with intramammary infections caused by non-aureus Staphylococcus, Aerococcus, Enterococcus, Lactococcus, and Streptococcus species.

The objective of this prospective cohort study was to explore associations between intramammary infection (IMI) in late-lactation cows and postcalving udder health and productivity. Cows (n = 2,763) from 74 US dairy herds were recruited as part of a previously published cross-sectional study of bedding management and IMI in late-lactation cows. Each herd was visited twice for sampling. At each visit, aseptic quarter milk samples were collected from 20 cows approaching dry-off (>180 d pregnant), which were cultured using standard bacteriological methods and MALDI-TOF for identification of isolates. Quarter-level culture results were used to establish cow-level IMI status at enrollment. Cows were followed from enrollment until 120 d in milk (DIM) in the subsequent lactation. Herd records were used to establish whether subjects experienced clinical mastitis or removal from the herd, and DHIA test-day data were used to record subclinical mastitis events (somatic cell count >200,000 cells/mL) and milk yield (kg/d) during the follow-up period. Cox regression and generalized estimating equations were used to evaluate the associations between IMI and the outcome of interest. The presence of late-lactation IMI caused by major pathogens was positively associated with postcalving clinical mastitis [hazard ratio = 1.5, 95% confidence interval (CI): 1.2, 2.0] and subclinical mastitis (risk ratio = 1.5, 95% CI: 1.3, 1.9). Species within the non-aureus Staphylococcus (NAS) group varied in their associations with postcalving udder health, with some species being associated with increases in clinical and subclinical mastitis in the subsequent lactation. Late-lactation IMI caused by Streptococcus and Streptococcus (Strep)-like organisms, other than Aerococcus spp. (i.e., Enterococcus, Lactococcus, and Streptococcus spp.) were associated with increases in postcalving clinical and subclinical mastitis. Test-day milk yield from 1 to 120 DIM was lower (-0.9 kg, 95% CI: -1.6, -0.3) in late-lactation cows with any IMI compared with cows without IMI. No associations were detected between IMI in late lactation and risk for postcalving removal from the herd within the first 120 DIM. Effect estimates reported in this study may be less than the underlying quarter-level effect size for IMI at dry-off and postcalving clinical and subclinical mastitis, because of the use of late-lactation IMI as a proxy for IMI at dry-off and the use of cow-level exposure and outcome measurements. Furthermore, the large number of models run in this study (n = 94) increases the chance of identifying chance associations. Therefore, confirmatory studies should be conducted. We conclude that IMI in late lactation may increase risk of clinical and subclinical mastitis in the subsequent lactation. The relationship between IMI and postcalving health and productivity is likely to vary among pathogens, with Staphylococcus aureus, Streptococcus spp., Enterococcus spp., and Lactococcus spp. being the most important pathogens identified in the current study.

Randomized controlled non-inferiority trial investigating the effect of 2 selective dry-cow therapy protocols on antibiotic use at dry-off and dry period intramammary infection dynamics.

Selective dry-cow therapy (SDCT) could be used to reduce antibiotic use on commercial dairy farms in the United States but is not yet widely adopted, possibly due to concerns about the potential for negative effects on cow health. The objective of this study was to compare culture- and algorithm-guided SDCT programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure, non-inferiority trial for the following quarter-level outcomes: antibiotic use at dry-off, dry period intramammary infection (IMI) cure risk, dry period new IMI risk, and IMI risk at 1 to 13 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by treating only quarters from which aseptically collected milk samples tested positive on the Minnesota Easy 4Cast plate (University of Minnesota, St. Paul, MN) after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow had either a Dairy Herd Improvement Association test somatic cell count >200,000 cells/mL during the current lactation or 2 or more clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Intramammary infection status at enrollment and at 1 to 13 DIM was determined using standard bacteriological methods. The effect of treatment group on dry period IMI cure, dry period new IMI, and IMI risk at 1 to 13 DIM was determined using generalized linear mixed models (logistic), with marginal standardization to derive risk difference (RD) estimates. Quarter-level antibiotic use at dry-off for each group was BDCT (100%), cult-SDCT (45%), and alg-SDCT (45%). The crude dry period IMI cure risk for all quarters was 87.5% (818/935), the crude dry period new IMI risk was 20.1% (764/3,794), and the prevalence of IMI at 1 to 13 DIM was 23% (961/4,173). Non-inferiority analysis indicated that culture- and algorithm-guided SDCT approaches performed at least as well as BDCT for dry period IMI cure risk. In addition, the final models indicated that the risks for each of the 3 IMI measures were similar between all 3 treatment groups (i.e., RD estimates and 95% confidence intervals all close to 0). These findings indicate that under the conditions of this trial, culture- and algorithm-guided SDCT can substantially reduce antibiotic use at dry-off without negatively affecting IMI dynamics.

Randomized equivalence study comparing the efficacy of 2 commercial internal teat sealants in dairy cows.

The use of an internal teat sealant (ITS) at dry-off has been repeatedly shown to improve udder health in the subsequent lactation. However, almost all ITS research conducted in North America has evaluated one product (Orbeseal, Zoetis, Parsippany, NJ). The objective of this study was to evaluate a new ITS product (Lockout, Boehringer-Ingelheim Animal Health, Duluth, GA), by comparing it directly to Orbeseal in a multi-site, randomized, positively controlled equivalence trial for health indicators during the dry period [quarter-level new intramammary infection (IMI) risk, IMI cure risk, and IMI risk at 1 to 13 d in milk, DIM] and during the first 100 DIM [clinical mastitis and culling or death risk and test-day milk somatic cell count (SCC) and milk yield]. At dry-off, cows were randomly allocated to be treated with Orbeseal or Lockout after blanket administration of a cloxacillin dry cow therapy product. Cows were then followed from dry-off until 100 DIM. Intramammary infection status at enrollment and at 1 to 13 DIM was determined using standard bacteriological methods, allowing for the measurement of IMI dynamics during the dry period (i.e., IMI cures and new IMI). The effect of ITS group on dry period IMI cure, dry period new IMI, and IMI risk at 1 to 13 DIM was determined using generalized linear mixed models (logistic). Marginal standardization was used to derive risk difference estimates. An equivalence hypothesis test was conducted to compare ITS groups for dry period new IMI risk (margin of equivalence was ±5% units). The effect of ITS group on clinical mastitis and culling or death was determined using Cox proportional hazards regression. The effect of ITS group on test-day SCC and milk yield was determined using linear mixed models. Final models indicated that measures of quarter-level IMI dynamics were similar between ITS groups (i.e., risk difference estimates and 95% confidence intervals all close to zero). Furthermore, Lockout was found to be equivalent to Orbeseal for dry period new IMI risk using an equivalence hypothesis test. Hazard ratio estimates for clinical mastitis and culling or death were close to 1 and differences in SCC and milk yield between ITS groups were close to 0, indicating negligible effects of ITS group on test-day SCC and milk yield. In most cases, these effect estimates were relatively precise (i.e., narrow 95% confidence intervals). We conclude that producers using blanket dry cow therapy could consider including Orbeseal or Lockout treatment in their programs.

Randomized controlled trial investigating the effect of 2 selective dry-cow therapy protocols on udder health and performance in the subsequent lactation.

The objective of this study was to compare culture- and algorithm-guided selective dry-cow therapy (SDCT) programs with blanket dry-cow therapy (BDCT) in a multi-site, randomized, natural exposure clinical trial for the following cow-level outcomes: clinical mastitis, removal from the herd, and Dairy Herd Improvement Association (DHIA) test-day milk yield and SCC measures during the first 120 d in milk (DIM). Two days before planned dry-off, cows in each of 7 herds were randomly allocated to BDCT, culture-guided SDCT (cult-SDCT), or algorithm-guided SDCT (alg-SDCT). At dry-off, BDCT cows received an intramammary antibiotic (500 mg of ceftiofur hydrochloride) in all 4 quarters. Antibiotic treatments were selectively allocated to quarters of cult-SDCT cows by only treating quarters from which aseptically collected milk samples tested positive on a rapid culture system after 30 to 40 h of incubation. For alg-SDCT cows, antibiotic treatments were selectively allocated at the cow level, with all quarters receiving antibiotic treatment if the cow met at least one of the following criteria: (1) any DHIA test with a somatic cell count >200,000 cells/mL during the current lactation, and (2) ≥2 clinical mastitis cases during the current lactation. All quarters of all cows were treated with an internal teat sealant. Clinical mastitis and removal from the herd events (i.e., culling or death) and DHIA test-day data from dry-off to 120 DIM were extracted from herd records. Hazard ratios (HR) for the effect of treatment group on clinical mastitis and removal from the herd during 1 to 120 DIM were determined using Cox proportional hazards regression. The effects of treatment group on test-day loge-transformed SCC and milk yield were determined using linear mixed models. Final models indicated that either SDCT program was unlikely to increase clinical mastitis risk (HRcult-SDCT/BDCT = 0.82, 95% CI: 0.58, 1.15; HRalg-SDCT/BDCT = 0.83, 95% CI: 0.63, 1.09) or test-day logeSCC (cult-SDCT minus BDCT = 0.05, 95% CI: -0.09, 0.18; alg-SDCT minus BDCT = 0.07, 95% CI: -0.07, 0.21). Risk of removal from the herd and test-day milk yield were similar between treatment groups. Findings from this study indicate that culture- or algorithm-guided SDCT can be used at dry-off without negatively affecting cow health and performance in early lactation.

Cross-sectional study of the relationships among bedding materials, bedding bacteria counts, and intramammary infection in late-lactation dairy cows.

Objectives of this study were to (1) describe the intramammary infection (IMI) prevalence and pathogen profiles in quarters of cows approaching dry-off in US dairy herds, (2) compare IMI prevalence in quarters of cows exposed to different bedding material types, and (3) identify associations between bedding bacteria count and IMI in cows approaching dry-off. Eighty herds using 1 of 4 common bedding materials (manure solids, organic non-manure, new sand, and recycled sand) were recruited in a multi-site cross-sectional study. Each herd was visited twice for sampling. At each visit, aseptic quarter-milk samples were collected from 20 cows approaching dry-off (>180 d pregnant). Samples of unused and used bedding were also collected. Aerobic culture was used to determine the IMI status of 10,448 quarters and to enumerate counts (log10 cfu/mL) of all bacteria, Staphylococcus spp., Streptococcus spp. and Streptococcus-like organisms (SSLO), coliforms, Klebsiella spp., noncoliform gram-negatives, Bacillus spp., and Prototheca spp. in unused (n = 148) and used (n = 150) bedding. The association between bedding bacteria count and IMI was determined using multivariable logistic regression with mixed effects. Quarter-level prevalence of IMI was 21.1%, which was primarily caused by non-aureus Staphylococcus spp. (11.4%) and SSLO (5.6%). Only modest differences in IMI prevalence were observed between the 4 common bedding material types. Counts of all bacteria in unused bedding was positively associated with odds of IMI caused by any pathogen [ALL-IMI; odds ratio (OR) = 1.08]. A positive association was also observed for counts of SSLO in unused bedding and SSLO-IMI (OR = 1.09). These patterns of association were generally consistent across the 4 common bedding materials. In contrast, the association between counts of all bacteria in used bedding and ALL-IMI varied by bedding type, with positive associations observed in quarters exposed to manure solids (OR = 2.29) and organic non-manure (OR = 1.51) and a negative association in quarters exposed to new sand (OR = 0.47). Findings from this study suggest that quarter-level IMI prevalence in late-lactation cows is low in US dairy herds. Furthermore, bedding material type may not be an important risk factor for IMI in late lactation. Higher levels of bacteria in bedding may increase IMI prevalence at dry-off in general, but this relationship is likely to vary according to bedding material type.

Cross-sectional study of the relationship between cloth udder towel management, towel bacteria counts, and intramammary infection in late-lactation dairy cows.

Because cloth udder towels (CUT) may function as a fomite for mastitis-causing pathogens, most udder health laboratories offer towel culture services as a tool to monitor towel hygiene. However, no studies have investigated if an association exists between bacteria levels in CUT and udder health outcomes. The objectives of this cross-sectional study were to (1) describe associations between herd-level measures of towel bacteria count (ToBC) and quarter-level intramammary infection (IMI) status in late-lactation cows, (2) establish pathogen-specific target levels of bacteria in CUT to aid the interpretation of towel culture reports, and (3) identify laundering-related risk factors for high ToBC. The study was conducted in 67 herds from 10 dairy states in the United States that used CUT. These 67 herds were originally recruited as part of a larger (80 herd) cross-sectional study of bedding management. Each herd was visited once during December 2017 to April 2018 and quarter-milk samples (n = 4,656) were collected from late-gestation (>180 d pregnant) cows (n = 1,313). Two recently laundered CUT were collected and a questionnaire was used to collect information about pre-milking teat preparation and CUT management practices. Quarter-level IMI status was determined using standard bacteriologic methods. In addition, colony-forming units of all bacteria (total bacteria), Staphylococcus spp., Streptococcus spp. or Streptococcus-like organisms (SSLO), coliforms, noncoliform gram-negatives, and Bacillus spp. were determined for each pair of CUT (log10 cfu/cm2). The association between ToBC and IMI was determined using multivariable logistic regression with mixed effects. After dichotomizing ToBC into high and low categories, associations between towel management practices and ToBC category were determined using unconditional logistic regression. The quarter-level prevalence of IMI was 19.6%, which was predominantly caused by non-aureus Staphylococcus spp. (NAS; 10.2%) and SSLO (5.1%). The predominant bacteria in CUT were Bacillus spp. (median = 3.13 log10 cfu/cm2). Total bacteria count was not associated with odds of IMI (odds ratio = 1.06), likely due to the predominance of Bacillus spp. in CUT and low number of IMI caused by Bacillus spp. In contrast, counts of Staphylococcus spp. and SSLO were positively associated with odds of IMI caused by NAS (odds ratio = 1.33) and SSLO (odds ratio = 1.45), respectively. Of 12 CUT management practices evaluated, only the failure to use a dryer was identified as a clear predictor of risk for a high ToBC (risk ratio of high coliform count = 8.17). Our study findings suggest that CUT may act as a fomite for NAS and SSLO. We recommend that herds aim to keep counts of Staphylococcus spp. and SSLO in CUT below 32 cfu/cm2 (or 5 cfu/in2), and that laundered towels be completely dried in a hot air dryer.

Relationships among bedding materials, bedding bacteria counts, udder hygiene, milk quality, and udder health in US dairy herds.

Bedding is an important source of teat end exposure to environmental mastitis pathogens. To better control environmental mastitis, we need an improved understanding of the relationships among bedding selection and management, bedding bacteria counts (BBC), and udder health (UH). The objectives of this cross-sectional observational study were (1) to describe BBC, bedding characteristics, udder hygiene scores, bulk tank milk (BTM) quality, and UH in US dairy herds using 1 of 4 bedding materials; (2) describe the relationship between BBC and herd measures of UH; and (3) identify benchmarks for monitoring bedding hygiene. Local dairy veterinarians and university researchers enrolled and sampled 168 herds from 17 states. Herds were on a Dairy Herd Improvement Association (DHIA) testing program and used 1 of 4 bedding types for lactating cows: new sand, reclaimed sand, manure solids (MNS), or organic non-manure materials. Each herd was sampled twice (winter and summer) in 2016. Samples and data collected included unused and used bedding, BTM samples, udder hygiene scores, DHIA test data, and descriptions of facilities and herd management practices. Bedding was cultured to determine the total bacteria count and counts of Bacillus spp., coliforms, Klebsiella spp., non-coliform gram-negative organisms, streptococci or streptococci-like organisms (SSLO), and Staphylococcus spp. Bedding dry matter, organic matter, and pH were also measured. Bulk tank milk samples were cultured to determine counts of coliforms, NAS, SSLO, Staphylococcus aureus, and Mycoplasma spp. Udder health measures included DHIA test-day average linear score (LS); the proportion of cows with an intramammary infection (IMI), where infection was defined as LS ≥4.0; the proportion of cows with a new IMI, where new IMI was defined as LS changing from <4.0 to ≥4.0 in the last 2 tests; the proportion of cows with a chronic infection, where chronic was defined as LS ≥4.0 on the last 2 tests; and the cumulative incidence of clinical mastitis in the 30-d period preceding sample collection. Although much variation existed within and among bedding types, mixed linear regression showed the use of MNS bedding to be generally associated with higher BBC, dirtier udders, increased coliform and SSLO counts in BTM, and poorer UH measures compared with organic non-manure materials, reclaimed sand, or new sand bedding materials. While controlling for important farm traits and management practices, mixed linear regression showed that increased counts of coliforms, Klebsiella spp., SSLO, and Staphylococcus spp. in both unused and used bedding were associated with poorer values for 1 or more herd-level measures of UH. Achievable benchmarks identified for counts of coliforms (unused: ≤500 cfu/cm3; used: ≤10,000 cfu/cm3), Klebsiella spp. (0 cfu/cm3 for unused and used), Staphylococcus spp. (0 cfu/cm3 for unused and used), and SSLO (unused: 0 cfu/cm3; used: ≤500,000 cfu/cm3) can be used to monitor bedding hygiene in most bedding materials, with minor variations suggested for SSLO in unused MNS (≤1,000 cfu/cm3).

Physical behavior and associations with health outcomes in operable NSCLC patients: A prospective study.

OBJECTIVES: Our objectives were to 1) characterize daily physical behavior of operable non-small cell lung cancer (NSCLC) patients, from preoperative to six months postoperative using accelerometry, and explore if physical behavior preoperative or one month postoperative is associated with better health outcomes at six months postoperative. METHODS: A prospective study with 23 patients (13 female) diagnosed with primary NSCLC and scheduled for curative lung resection was performed. Outcome measures were assessed two weeks preoperative, and one, three and six months postoperative, and included accelerometer-derived physical behavior measures and the following health outcomes: six minute walking distance (6MWD), questionnaires concerning health-related quality of life (HRQOL), fatigue and distress. RESULTS: On group average, physical behavior showed significant changes over time. Physical behavior worsened following surgery, but improved between one and six months postoperative, almost reaching preoperative levels. However, physical behavior showed high variability between patients in both amount as well as change over time. More time in moderate-to-vigorous physical activity in bouts of 10 min or longer in the first month postoperative was significantly associated with better 6MWD, HRQOL, distress, and fatigue at six months postoperative. CONCLUSION: As expected, curative lung resection impacts physical behavior. Patients who were more active in the first month following surgery reported better health outcome six months postoperative. The large variability in activity patterns over time observed between patients, suggests that physical behavior 'profiling' through detailed monitoring of physical behavior could facilitate tailored goal setting in interventions that target change in physical behavior.

Management goals for type 1 Gaucher disease: An expert consensus document from the European working group on Gaucher disease.

Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions [obtained by patient- reported outcome measurements (PROMs)] is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.

Evaluation of an automated milk leukocyte differential test and the California Mastitis Test for detecting intramammary infection in early- and late-lactation quarters and cows.

Study objectives were to (1) describe the diagnostic test characteristics of an automated milk leukocyte differential (MLD) test and the California Mastitis Test (CMT) to identify intramammary infection (IMI) in early- (EL) and late-lactation (LL) quarters and cows when using 3 different approaches to define IMI from milk culture, and (2) describe the repeatability of MLD test results at both the quarter and cow level. Eighty-six EL and 90 LL Holstein cows were sampled from 3 Midwest herds. Quarter milk samples were collected for a cow-side CMT test, milk culture, and MLD testing. Quarter IMI status was defined by 3 methods: culture of a single milk sample, culture of duplicate samples with parallel interpretation, and culture of duplicate samples with serial interpretation. The MLD testing was completed in duplicate within 8 h of sample collection; MLD results (positive/negative) were reported at each possible threshold setting (1-18 for EL; 1-12 for LL) and CMT results (positive/negative) were reported at each possible cut-points (trace, ≥1, ≥2, or 3). We created 2 × 2 tables to compare MLD and CMT results to milk culture, at both the quarter and cow level, when using each of 3 different definitions of IMI as the referent test. Paired MLD test results were compared with evaluate repeatability. The MLD test showed excellent repeatability. The choice of definition of IMI from milk culture had minor effects on estimates of MLD and CMT test characteristics. For EL samples, when interpreting MLD and CMT results at the quarter level, and regardless of the referent test used, both tests had low sensitivity (MLD = 11.7-39.1%; CMT = 0-52.2%) but good to very good specificity (MLD = 82.1-95.2%; CMT = 68.1-100%), depending on the cut-point used. Sensitivity improved slightly if diagnosis was interpreted at the cow level (MLD = 25.6-56.4%; CMT = 0-72.2%), though specificity generally declined (MLD = 61.8-100%; CMT = 25.0-100%) depending on the cut-point used. For LL samples, when interpreted at the quarter level, both tests had variable sensitivity (MLD = 46.6-84.8%; CMT = 9.6-72.7%) and variable specificity (MLD = 59.2-79.8%; CMT = 52.5-97.3%), depending on the cut-point used. Test sensitivity improved if interpreted at the cow level (MLD = 59.6-86.4%; CMT = 19.1-86.4%), though specificity declined (MLD = 32.4-56.8%; CMT = 14.3-92.3%). Producers considering adopting either test for LL or EL screening programs will need to carefully consider the goals and priorities of the program (e.g., whether to prioritize test sensitivity or specificity) when deciding on the level of interpretation (quarter or cow) and when selecting the optimal cut-point for interpreting test results. Additional validation studies and large randomized field studies will be needed to evaluate the effect of adopting either test in selective dry cow therapy or fresh cow screening programs on udder health, antibiotic use, and economics.

Ambulant monitoring and web-accessible home-based exercise program during outpatient follow-up for resected lung cancer survivors: actual use and feasibility in clinical practice.

PURPOSE: The aim of this study is to evaluate the feasibility of a telehealthcare application for operable lung cancer (OLC) patients, consisting of ambulant symptom and physical activity monitoring (S&PAM) and a web-accessible home-based exercise program (WEP), and identify possible barriers for successful adoption and implementation. METHODS: A two-stage mixed methods design was used, in which 22 OLC patients and their treating healthcare professionals (HCPs) participated from pre-surgery to three (stage 1; n = 10) or six (stage 2; n = 12) months post-surgery. Actual use and acceptability (usability, usefulness, and satisfaction) were evaluated. RESULTS: Seventeen OLC patients (age (SD): 59 (8) years; 8 female) actively used the modules. S&PAM use varied from 1 to 11 monitoring days prior to outpatient consultations. Patients used WEP most frequently during the first 5 weeks, with an average of four logins a week. Fifty-eight percent used WEP beyond 7 weeks. No adverse situations occurred, and patients felt confident using the applications. Perceived added value included active lifestyle promotion, decreased anxiety, and accessibility to specialized HCPs. Physiotherapists used WEP as intended. Contrarily, physicians scarcely used information from S&PAM. To promote future adoption, strategies should focus on high-level patient tailoring of the technology, and formalization of including the applications in the clinical workflow. CONCLUSIONS: Ambulant monitoring and web-accessible home exercise is clinically feasible for OLC patients. However, low level of adoption by referring physicians may hamper successful implementation. IMPLICATIONS FOR CANCER SURVIVORS: Patients perceived both ambulant monitoring and web-accessible exercise as an added value to regular care and feasible to use in the period before and after lung resection.

Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations.

BACKGROUND: A high prevalence of contact dermatitis (CD) and respiratory symptoms has been observed in the construction industry, probably due to widespread exposure to irritants and allergens. It is unknown whether carriers of loss-of-function mutations in the gene encoding filaggrin (FLG), a known risk gene for eczema and asthma, are at increased risk. OBJECTIVES: To investigate associations of FLG mutations with CD and respiratory symptoms in Dutch construction workers. METHODS: A questionnaire including items on dermal and respiratory symptoms such as wheeze, shortness of breath and asthma was administered to construction workers. Total and specific serum IgE was analysed by enzyme immunoassays. Four FLG loss-of-function mutations were genotyped. CD was diagnosed by a team of a dermatologist and a clinical occupational medicine specialist using photographs of the subjects' hands and self-reported questionnaire data. RESULTS: Of the 506 participating workers, 6·3% carried at least one FLG mutation. Mild CD was diagnosed by the specialists in 34·0%, and severe CD in an additional 24·3%. CD was considered work related in 282 of 295 subjects (95·6%). Carriers of FLG variants had an increased risk of CD compared with subjects carrying wild-type alleles [mild CD: odds ratio (OR) 5·71, 95% confidence interval (CI) 1·63-20·06; severe CD: OR 8·26, 95% CI 2·32-29·39]. FLG variants and the presence of CD were not associated with respiratory symptoms and atopy. CONCLUSIONS: Contact dermatitis prevalence in construction workers is high. FLG loss-of-function mutations increase the risk of CD even further. FLG mutations were not associated with respiratory symptoms or atopy.

Relationship between patterns of daily physical activity and fatigue in cancer survivors.

PURPOSE: This study investigated: (1) physical activity behaviour of cancer survivors throughout the day, (2) the relationship between objective and subjective measures of physical activity, and (3) the relationship between daily physical activity and fatigue. METHOD: Physical activity was measured objectively using 3D-accelerometry (expressed in counts per minute (cpm)), and subjectively using a Visual Analogue Scale (VAS; 0-10) implemented on a smartphone in 18 cancer survivors (6 male; age 55.7 ± 10.2 yrs; free from cancer, last treatment ≥three months previously), and matched controls. Fatigue was scored thrice daily on a smartphone (0-10 VAS). RESULTS: Mean daily physical activity of cancer survivors did not deviate from controls (1108 ± 287 cpm versus 1223 ± 371 cpm, p = .305). However, in cancer survivors physical activity significantly decreased from morning to evening (p < .01) and increased levels of fatigue throughout the day were reported (p < .01). Furthermore, a positive correlation was found between levels of fatigue and the magnitude of the decline in physical activity from afternoon to evening (p < .05). Objective and subjective measured physical activity showed low correlations. CONCLUSIONS: This study demonstrated imbalanced activity patterns in cancer survivors. Also, the more a survivor felt fatigued, the greater the decline in activity behaviour throughout the day. The low correlation between objective and subjective physical activity suggests low awareness in cancer survivors about their daily physical activity performed. Ambulatory monitoring provides new insights in both patterns of physical activity and fatigue, which might be a valuable tool to provide activity management more efficiently during treatment of fatigue.

Evaluation of the Minnesota Easy Culture System II Bi-Plate and Tri-Plate for identification of common mastitis pathogens in milk.

The objective of this study was to validate use of the Minnesota Easy Culture System II Bi-Plate and Tri-Plate (University of Minnesota Laboratory for Udder Health, St. Paul) to identify common mastitis pathogens in milk. A total of 283 quarter and composite milk samples submitted to the University of Minnesota Laboratory for Udder Health during the spring of 2010 were cultured simultaneously using 3 methods: standard laboratory culture (reference method) and the Minnesota Easy Culture System II Bi-Plate and Tri-Plate methods. Bi-Plate and Tri-Plate cultures were incubated for 18 to 24h and interpreted by 2 independent, untrained readers within 5h of each other. An experienced technician completed the standard laboratory culture. For each sample, all 3 study personnel recorded the culture result (yes/no) for each of the following diagnostic categories: no bacterial growth (NG), mixed (2 organisms), contaminated (3 or more organisms), gram-positive (GP), gram-negative (GN), Staphylococcus spp., Streptococcus spp., Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis, Enterococcus spp., Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Klebsiella spp., and other. For each category, the prevalence, sensitivity, specificity, accuracy, and predictive values of a positive and negative test were calculated, and the agreement between readers and between each reader and the laboratory was assessed. Specificity, overall accuracy, and negative predictive values were generally high (>80%) for the Bi-Plate and Tri-Plate for each category. Sensitivity and positive predictive values were intermediate (>60%) or high (>80%) for the broad categories of NG, GP, GN, Staphylococcus spp. and Streptococcus spp., and for Staph. aureus, but were generally lower (<60%) for other more specific categories. Similarly, interreader agreement (kappa value) was moderate to substantial (40-80%) for the broad categories of NG, GP, GN, Staphylococcus spp. and Streptococcus spp., and for Staph. aureus and E. coli, but was lower for other categories. The Tri-Plate had a higher sensitivity, accuracy, and negative predictive value for Streptococcus spp., and higher interreader agreement for some of the more specific categories. Our conclusion was that Bi-Plate and Tri-Plate results will be most reliable when used to classify infections in broad diagnostic categories such NG, GP, or GN. The Bi-Plate and Tri-Plate will have intermediate ability to identify infections as being caused by Staphylococcus spp., Streptococcus spp., or Staph. aureus.

SU-E-T-280: Optimal Angle for a Dual-Field Stanford Technique for TSET.

PURPOSE: This study examines the optimal angle for a dual-field Stanford technique for TSET at extended SSD (SSD= 1, 2, 3, 4, 5 m) to predict a readily available optimal angle for any SSD. METHODS: The optimal angle at various SSDs is found using detector array. The diode array consists of 9 diodes placed on a vertical board with a measured vertical scale with the origin placed at isocenter. The lateral distance ranges from -100 to +75 cm. A square 36×36 cm2 field is used to deliver dose in HDTSe- delivery mode with a dose rate 2500 MU/min from a Varian Clinic 2300IX linac. Several pairs of gantry angles for the dual field are used, with the first gantry being 70°-78° and the second being 110° -102°. These Result in a dual field of 90° ± θ (θ = 10° - 20°) to build a suitable flatness profile on the vertical axis for treatment. The best group is chosen to determine the optimal angle for each SSD considered. From these optimal angles, an algorithm is determined for any extended SSD treatment. RESULTS: It is found that the optimal angle for TSET does change as one varies the SSD. These angle groups are specific for each SSD giving definite markers for the algorithm. At an SSD of 5 m it has been shown that an optimal angle of θ = 106° produces the best flatness on the vertical axis. While at SSD of 4 m, 9 = 18° Conclusions: An algorithm can now be applied for any treatment center considering a dual- field Stanford technique for TSET simplifying the physics commissioning process for the center in consideration.

SU-E-T-147: Film Dosimetry Verification for TSE Using An Epson Scanner.

PURPOSE: To commission and verify an Epson scanner for film dosimetry for total skin electron beam therapy (TSEB). METHODS: Use data from an IBA PPC40 parallel-plate ion chamber and Sun Nuclear QED skin diode detectors as standard; we have made comparisons to the film measurement using Kodak XV films. Hurter-Driffield (HD) curve are established for 6 MeV total skin electron beams at a source-to-surface distance (SSD) of 5 m. Also HD curves are built for 6 MeV at a 100 cm SSD. Dose profiles for a series of oblique incident large electron fields are measured using the film for approximately 80 cGy dose delivered at the peak. The film is then scanned using two scanners, an Epson expression 10000 XL and a Vidar VXR-16 Dosimetry Pro. The optimal scanning conditions (e.g., dot per pixel size, internal color correction scheme) are chosen for the Epson scanner. Matlab is then used to analyze the optical density (OD) of the scanned films. A transmission densitometer made by Tobias Associates transmission is used to analyze the films to give a classical standard. RESULTS: The analysis of the Epson scanner is presented in two forms: one with and one without the HD correction from the established HD curve. The error analysis gives an uncertainty of 5% without the HD correction. An improved result of approximately 3% is found when an HD correction is applied to the analysis. CONCLUSIONS: A simple Epson scanner satisfies the commissioning standards for TSEB when an HD curve correction is applied.

Developing transboundary river basin monitoring programmes using the DPSIR indicator framework.

Policymakers are often dissatisfied by the lack of what they consider useful information to support water management. Analysis of this 'water information gap' shows that this is caused by a lack of proper communication between information users and information producers. To improve this communication the process of specification of information needs has been structured. Earlier experiences showed that this not only entailed developing a structure to manage the process, but also developing a structure to guide the breakdown of policy objectives into information needs. Such a structure to organise the problem supports policy makers and monitoring specialists in their communication. This paper describes three pilot projects where the DPSIR indicator framework was used to organise the problem. It is concluded that the DPSIR framework is useful for improving the communication between information users and information producers and is helpful in breaking down policy objectives into information needs in a structured way. The structured approach in this way assists in narrowing the water information gap. Use of the DPSIR framework however leads to a bias towards water management problems and does not provide for all the relevant information needs.

A methodology to bridge the water information gap.

The metaphor of the water information gap is used to describe the discontent between information users and information producers about the use of and need for specific information. This paper describes the rugby-ball methodology for specification of information needs that was developed on the basis of an analysis of the water information gap and insights from the literature on policy- and decision-analysis, problem-structuring, and information management. The methodology consists of a process-architecture to manage the process of assessing information needs and a structure to organise the information needs related to water policy objectives. The methodology was developed and enhanced through a Reflection-in-Action process in which interaction between ideas and practice leads to improved results. The paper describes the methodology and its development, and concludes both on the development process and on the abilities of the methodology to narrow the water information gap.