A cross-sectional field study on potential associations between feed quality measures and usage of antimicrobials in commercial mink (Neovison vison).

Feed quality is generally assumed to affect health status in animal production. In previous studies, the feed producer has been found to affect the occurrence of gastrointestinal disease and antimicrobial use in Mink (Neovison vison). Mink are fed with moist, freshly produced feed, based on perishable ingredients. The objective of this study was to investigate the potential effect of specific feed parameters on antimicrobial use on herd level. The study was cross-sectional, including 1472 mink herds, responsible for 97% of oral antimicrobials prescribed for Danish mink during the study period, 2012-2014. Data were obtained from the national veterinary prescription database (VetStat), Kopenhagen Fur database, and the Voluntary Feed Control (Mink producers Organization). All feed batches subject to feed control were included. A multi-variable variance analysis was carried out analysing the effect of the feed parameters total volatile nitrogen, dry matter, crude protein and fat; total bacterial count (21°C), and counts of sulphite producing bacteria (21°C), Clostridium spp., faecal cocci (FC) (44°C), yeast, and mould; presence of Salmonella spp. and Clostridium perfringens (dichotome). Three outcome variables were applied: prescription of oral antimicrobial on herd level within time slots of 3, 5 or 7days after feeding of an included batch. Two binomial models were developed, adjusting for significant effects (p<0.0001) of Ps. aeruginosa infection, herd size, month (season) and year. Antimicrobial prescription was significantly (p<0.0001) associated with FC (all time slots, both models). A negative association (p<0.0001) with crude protein on antimicrobial prescription within a 7day slot suggested an association between low content of crude protein and antimicrobial use. The associations need to be confirmed in controlled studies, and ideally, potential causalities should be investigated. The perspective of such findings could be the development of tests for control of feed ingredients prior to use in the feed production.

Monte Carlo simulation of ruthenium eye plaques with GEANT4: influence of multiple scattering algorithms, the spectrum and the geometry on depth dose profiles.

Previous studies show remarkable differences in the simulation of electron depth dose profiles of ruthenium eye plaques. We examined the influence of the scoring and simulation geometry, the source spectrum and the multiple scattering algorithm on the depth dose profile using GEANT4. The simulated absolute dose deposition agrees with absolute dose data from the manufacturer within the measurement uncertainty. Variations in the simulation geometry as well as the source spectrum have only a small influence on the depth dose profiles. However, the multiple scattering algorithms have the largest influence on the depth dose profiles. They deposit up to 20% less dose compared to the single scattering implementation. We recommend researchers who are interested in simulating low- to medium-energy electrons to examine their simulation under the influence of different multiple scattering settings. Since the simulation and scoring geometry as well as the exact physics settings are best described by the source code of the application, we made the code publicly available.

Farm specific risk factors for Campylobacter colonisation in Danish and Norwegian broilers.

Campylobacteriosis has become the leading bacterial zoonosis in humans in the European Union and other developed countries. There are many sources of human Campylobacter infections, but broilers and broiler meat have been shown to be the most important. In order to implement effective interventions that reduce the probability of Campylobacter colonisation of broiler flocks, it is essential to fully understand the risk factors involved. We present a bi-national risk factor survey comprising Campylobacter data from more than 5200 Danish and Norwegian indoor, conventional broiler flocks and the responses to a standardised questionnaire, with more than 40 explanatory variables from 277 Danish and Norwegian farms. We explored several models by using different combinations of the Danish and Norwegian data, including models with single-country datasets. All models were analysed using a generalized linear model using backwards elimination and forward selection. The results show that Norwegian broiler flocks had a lower risk of being colonised than Danish flocks. Farm specific variables that increased the risk of flocks becoming colonised with Campylobacter in both countries were: broiler houses older than five years; longer downtime (no. of days between flocks), probably a consequence of longer downtimes being associated with less focus on maintaining a high biosecurity level; broiler houses without a separate ante-room or barrier; and the use of the drinker nipples with cups or bells compared with nipples without cups. Additional country specific risk factors were also identified. For Norway, the risk of colonisation increased with increasing numbers of houses on a farm and when the water used for the broilers originated from surface water or bore holes instead of mains. For Denmark, having boot dips or low stocking density increased the risk of a flock becoming Campylobacter positive. The different model approaches allowed us to explore the effect of having a large number of data available to identify the significant variables. To a large extent, the country specific models identified risk factors that were also found in the bi-national model. However, the bi-national model identified more risk factors than the country specific models. This indicated that combining the data sets from the two countries did not disrupt the results but was beneficial due to the greater strength achieved in the statistical analyses and the possibility of examining interactions terms with the variable Country.

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial.

Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

Factors associated with usage of antimicrobials in commercial mink (Neovison vison) production in Denmark.

The American mink (Neovison vison) is used for commercial fur production in Denmark. In recent years, antimicrobial prescription for Danish mink has been increasing. In this study, the patterns and trends in antimicrobial use in mink were described and a multi-variable variance analysis was carried out with the objective of identifying risk factors for antimicrobial use on herd level. The study was based on register data for 2007-2012. Information on antimicrobial use was obtained from the national database VetStat, monitoring all medicinal products used for animals on prescription level. Data on microbiological feed quality was obtained from the Voluntary Feed Control under the Mink producers Organization, and data on herd size and the relation between farm and feed producer was obtained from the registers at Kopenhagen Fur, based on yearly reporting from the mink producers. Descriptive analysis showed a clear significant effect of season on antimicrobial use, with a peak in "treatment proportions", TP (defined daily doses per kg biomass-days) in May, around the time of whelping, and a high level in the following months. In autumn, a minor peak in antimicrobial use occurred throughout the study period. From 2007 to 2011, a 102% increase in annual antimicrobial TP was noted; on herd level, the increase was associated with an increasing frequency of prescription, and a decrease in the amounts prescribed in months with prescription. A binomial model showed that on herd level, the annual number of months with antimicrobial prescription was significantly (p<0.01) affected by feed producer, veterinarian, disease (specific laboratory diagnosis) infection, herd size and year, with an interaction between feed producer and year. A log-normal model showed that in months with antimicrobial use, the TP on herd level was significantly (p<0.001) affected by year, month (season), feed producer, feed quality score, veterinarian, herd size and laboratory confirmed diagnosis of specific infections; additionally the interaction terms year×feed producer and herd size×month were significant (p<0.001). In conclusion, antimicrobial use on herd level was significantly associated with the microbiological food quality, the feed producer, and the veterinarian. The prescription patterns varied significantly between veterinarians, and some veterinarians were associated with both larger and more frequent prescriptions of antimicrobials at herd level. Herd size is associated with different prescription patterns. Finally, infection with Pseudomonas aeruginosa, astrovirus, influenza virus and Salmonella spp. was associated with an increase in antimicrobial use.

Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review.

Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case-control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23-34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the "possible" case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the "probable/definite" case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the "probable/definite" case definition. As the "possible" case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a "post-Lyme syndrome", could therefore be an artifact of unspecific case definitions in single studies.

Development of an Open-Source Tractor Driving Simulator for Tractor Stability Tests.

Developing devices for stability monitoring and rollover alerts is a promising possibility to prevent overturn events, which pose a severe risk to tractor operators. However, performing relevant tests with operators in the field is dangerous and impractical. As an alternative, this work identifies the challenges of simulating a tractor driving environment in a laboratory and details the solutions put in place to develop a tractor driving simulator at Penn State University. The simulator includes an instrumented tractor cab mounted on a custom motion base, a 2.43 m tall, 360° high-definition screen, a sound system, and a nine-computer network running open-source software that can be used to conduct experiments and simulate driving scenarios relevant to tractor instabilities. The system is used for an experiment that evaluates the driver's ability to perceive tilt angles at various tilt and roll combinations. Pilot-test results show that roll and pitch are systematically overestimated, producing perceptual errors that are unbiased, independent for roll and pitch, and typically have magnitudes of 4°. These results can aid the development of instability monitoring systems by considering human tilt perception to set alert thresholds. Future projects and applications of the tractor driving simulator are also discussed.

[Studies and Publication Practice in Pediatric Hematology and Oncology in Germany--An Analysis of the Period 1970-2006]. / Studien und Publikationspraxis in der PädiatrischenHämatologie und Onkologie in Deutschland--Analyseder Jahre 1970­2006.

BACKGROUND: Several therapy optimization studies (TOSs) for the treatment of hematologic and oncologic disorders in children and adolescents have been conducted in Germany. The publication of research results is necessary to ensure that future studies are well designed and based on relevant and unanswered questions. This retrospective cohort study was conducted to analyze the study- and publication practice in this field. METHODS: All study protocols in the field of the pediatric oncology and hematology in Germany were collected. Relevant data from study protocols were extracted, beginning with 1) general information about the study protocol, and 2) information about each methodological trial. In a second step, the publication practice was characterized by searching in electronic databases and by contacting principal investigators. Relevant Data of each publication was extracted. RESULTS: The research activity has increased significantly in the past few years. The found publication rate of 85% represents an outstanding publication practice. Additionally, German, as being the main publication language a few decades ago, has been almost completely replaced with English. An acceptable methodological conduct was observed in the analyzed study protocols. DISCUSSION AND CONCLUSION: Studies have been principally based on the concept of TOS, without considering a detailed breakdown into each methodological trial. A markedly subdivision of studies into methodologically identifiable trials would allow a clear definition of their parameters, while increasing transparency of the study conduct and its results.

Methodological quality of guidelines for management of Lyme neuroborreliosis.

BACKGROUND: Many aspects of clinical management of Lyme neuroborreliosis are subject to intense debates. Guidelines show considerable variability in their recommendations, leading to divergent treatment regimes. The most pronounced differences in recommendations exist between guidelines from scientific societies and from patient advocacy groups. Assessment of the methodological quality of these contradictory guideline recommendations can be helpful for healthcare professionals. METHODS: Systematic searches were conducted in MEDLINE and databases of four international and national guideline organizations for guidelines on Lyme neuroborreliosis published from 1999-2014. Characteristics (e.g., year of publication, sponsoring organization) and key recommendations were extracted from each guideline. Two independent reviewers assessed the methodological quality of each guideline according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. AGREE II scores from guidelines developed by scientific societies and from patient advocacy groups were compared across domains. RESULTS: We identified eight eligible guidelines of which n = 6 were developed by scientific societies and n = 2 by patient advocacy groups. Agreement on AGREE II scores was good (Cohen's weighted kappa = 0.87, 95% CI 0.83-0.92). Three guidelines, all from scientific societies, had an overall quality score of ≥ 50%. Two of them were recommended for use according to the AGREE II criteria. Across all guidelines, the AGREE II domain with the highest scores was "Clarity of Presentation" (65, SD 19%); all other domains had scores < 50% with the domain "Applicability" having the lowest scores (4, SD 4%). Guidelines developed by scientific societies had statistically significantly higher scores regarding clarity of presentation than guidelines from patient advocacy groups (p = 0.0151). No statistically significant differences were found in other domains. CONCLUSIONS: Current guidelines on Lyme neuroborreliosis vary in methodological quality and content. Health care providers and patients need to be aware of this variability in quality when choosing recommendations for their treatment decisions regarding Lyme neuroborreliosis. No statement can be given on quality of content and validity of recommendations, as these issues are not subject to assessment with the AGREE II tool and are prone to individual interpretation of the available evidence by the corresponding guideline panels. To enhance guideline quality, guideline panels should put more emphasis on linking recommendations to the available evidence, transparency in reporting how evidence was searched for and evaluated, and the implementation of recommendations into clinical practice.

Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review.

BACKGROUND AND PURPOSE: Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence-based clinical recommendations in a systematic review. METHODS: A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non-randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was 'residual neurological symptoms' whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta-lactam antibiotics in a meta-analysis regarding residual neurological symptoms at 4-12 months [risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98-1.63, P = 0.07] or adverse events (RR 0.82, 95% CI 0.54-1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10-2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38-0.84, P = 0.005). CONCLUSIONS: Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta-lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well-designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.

Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer.

Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI < 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.

Adjuvant sequential chemoradiation therapy in high-risk endometrial cancer: results of a prospective, multicenter phase-II study of the NOGGO (North-Eastern German Society of Gynaecological Oncology).

PURPOSE: The management of high-risk endometrial cancer (HREC) remains controversial. We conducted a prospective multicenter phase-II clinical trial to evaluate an adjuvant chemotherapy (CT) with sequential radiotherapy (RT) in patients with HREC. METHODS: Patients with HREC from 8 institutions in Germany were enrolled. After surgery, patients received four cycles of paclitaxel 175 mg/m² (P) and carboplatin AUC5 (C) (d1, q21d) and subsequent external pelvic radiation therapy (1.8 Gy/d, d1-5) at a total dose of 45 Gy with vaginal brachytherapy (3 × 5 Gy). Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints were tolerability, toxicity and QoL. Progression-free survival (PFS) was defined as secondary endpoint. RESULTS: Thirty-five patients were enrolled from 2004 through 2008. Median follow-up was 24 months (range 3-24 months). All patients received 4 cycles of P and C and completed RT. Overall, grade 3/4 haematological toxicity was 25.6 %. Three cycles were delayed because of leukopenia. Grade 3/4 non-haematologic toxicities were rare (≤3 %). No overall change in QoL occurred during treatment. Two-year median PFS and OS rates were both 75.8 %. CONCLUSIONS: Adjuvant combination CT with P + C and sequential RT is well tolerated and a feasible regimen in patients with HREC. Subsequent phase-III trials are warranted.

Analysis of factors important for the occurrence of Campylobacter in Danish broiler flocks.

For more than a decade human campylobacteriosis has been the leading zoonosis in many developed countries. Consumption of poultry or poultry products has been identified as the primary source of infection in humans. This study was conducted to identify risk factors for the occurrence of Campylobacter in Danish broiler flocks. The study was based on a large data set consisting of Campylobacter positive status for nearly 6000 broiler flocks and 43 explanatory variables. Data were obtained from the Danish Campylobacter surveillance programme in poultry and from the responses to a standardized questionnaire answered via interviews with broiler farm owners. Two hundred and forty broiler farms, comprising 539 broiler houses, were included in the study and their Campylobacter status was followed over a 2-year period (1999-2000). The large number of observations made it possible to carry out a multivariate analysis including all 43 variables. A multivariate analysis was conducted using a generalized linear model, and the correlations between the houses from the same farms were accounted for by adding a variance structure to the model. The procedures for analyses included backward elimination, forward selection and expanding of the number of observations used in the variance analysis along with the reduction of the number of parameters in the model. The unit of analysis was 'broiler house', meaning that all results from a broiler house were aggregated into one prevalence figure (number of positive flocks/total number of flocks delivered over the 2-year period). The following factors were found to be significantly associated with the occurrence of Campylobacter in the broiler flocks: old broiler houses, late introduction of whole wheat in the feed, relatively high broiler age at slaughter, improper rodent control, large number of chimneys on the broiler house, farm located in an area with a high density of cattle farms, having more than one broiler house on the farm, and improper storage of wheat. This large-scale study confirms several risk factors identified in previous studies. The results concerning chimneys may be explained by the easier access that flies have to the broiler houses, which seems in agreement with recent Danish studies on the significance of fly-screens to reduce Campylobacter in broiler flocks. The results of this study may be used in identification of effective interventions aimed at controlling Campylobacter in Danish broiler flocks.

Participation in the SUCCESS-A Trial Improves Intensity and Quality of Care for Patients with Primary Breast Cancer.

The SUCCESS-A trial is a prospective, multicenter, phase III clinical trial for high-risk primary breast cancer. It compares disease-free survival after randomization in patients treated with fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) with that of patients treated with 3 cycles of FEC followed by 3 cycles of gemcitabine and docetaxel (FEC-DG). After a second randomization patients were treated with zoledronate for 2 or 5 years. A total of 251 centers took part in the trial and 3754 patients were recruited over a period of 18 months which ended in March 2007. In a questionnaire-based survey we investigated the impact of enrollment in the trial on patient care, the choice of chemotherapy protocol and access to current oncologic information as well as overall satisfaction in the respective centers. Analysis of the 78 questionnaires returned showed that 40 % of the centers had never previously enrolled patients with these indications in clinical studies. Prior to participating in the study, 4 % of the centers prescribed CMF or other protocols in patients with high-primary breast cancer risk, 46 % administered anthracycline-based chemotherapy and 50 % gave taxane-based chemotherapy. Around half of the participating centers noted that intensity of care and overall quality of care became even better and that access to breast cancer-specific information improved through participation in the trial. After their experience with the SUCCESS-A trial, all of the centers stated that they were prepared to enroll patients in clinical phase III trials again in the future. These data indicate that both patients and physicians benefit from clinical trials, as enrollment improves treatment strategies and individual patient care, irrespective of study endpoints.

Weekly Paclitaxel plus Capecitabine versus Docetaxel Every 3 Weeks plus Capecitabine in Metastatic Breast Cancer.

Background. We performed a randomized phase II study comparing efficacy and toxicity of weekly paclitaxel 80 mg/m(2) (Weetax) with three weekly docetaxel 75 mg/m(2) (Threetax), both in combination with oral capecitabine 1000 mg/m(2) twice daily for 2 weeks followed by a 1-week break. Patients. Thirty-seven women with confirmed metastatic breast cancer were randomized. Results. Median TTF was 174 (Weetax) versus 147 days (Threetax) (P=0.472). Median OS was 933 (Weetax) versus 464 days (Threetax) (P=0.191). Reasons for TTF were PD 8/18 (Weetax), 9/19 (Threetax); and toxicity: 8/18 (Weetax), 8/19 (Threetax). ORR was 72% (Weetax) versus 26% (Threetax) (P = 0.01). The Threetax-combination resulted in a higher incidence of leuco-/neutropenia compared to Weetax. Grade II anemia was more pronounced in the Weetax group. No difference was found in quality of life. Conclusion. Taxanes in combination with capecitabine resulted in a high level of toxicity. Taxanes and capecitabine should be considered given sequentially and not in combination.

Prognostic relevance of disseminated tumor cells in the bone marrow of patients with primary breast cancer--results of a standardized follow-up.

BACKGROUND: The prognostic significance of disseminated tumor cells from bone marrow (BM-DTCs) of breast cancer patients has been demonstrated previously. In this study, data of a standardized long term follow-up of 829 patients with examination of BM-DTCs at primary diagnosis are presented. PATIENTS AND METHODS: BM aspiration and immunocytochemical examination of DTCs was performed according to a standardized protocol. Follow-up data of all patients were adjusted with the cancer registries of southern Bavaria. RESULTS: A total of 268 patients (32%) had BM-DTCs with a median of 2 (1-1223)/2 x 106 cells. Positive BM findings correlated with tumor size (p=0.032), but not with other histopathological parameters. After a median follow-up of 73 months, BM-DTCs were highly relevant for the development of distant metastases (p=0.006) and, beneath standard histological parameters, reduced overall survival (p=0.038). CONCLUSION: These results confirm the prognostic relevance of the detection of BM-DTCs. Newer methods, such as detection of circulating tumor cells in blood, will have to demonstrate comparable prognostic information in the future.

Survival of Salmonella on cuts of beef carcasses subjected to dry aging.

AIMS: The aim of this study was to determine the survival of 15 different strains of Salmonella of selected serotypes during prolonged cold storage of beef. METHODS AND RESULTS: Fifteen strains of eight different serotypes of Salmonella were spiked onto fresh cuts beef portions, and the survival was followed during storage in a laboratory cooling system. Over a 14-day period, all strains were reduced significantly in numbers; however, strains of Salmonella Typhimurium DT104 and Salmonella Enteritidis PT4 and PT8 survived significantly longer than strains of the serovars Dublin, Derby, Infantis and Newport. For five selected strains, the observations were verified in a pilot plant cooling facility mimicking industrial cooling. No significant differences in reduction were found between the two cooling methods. CONCLUSIONS: A significant reduction in Salmonella can be obtained by dry aging of beef during cold storage but the survival is strain dependent. SIGNIFICANCE AND IMPACT OF THE STUDY: From a hygienic point of view, cold storage of unpacked beef, which is still performed in small slaughterhouses, is a good alternative to vacuum packaging.

Inhibin A is down-regulated during chemotherapy in patients with breast cancer.

BACKGROUND: Inhibins are dimeric glycoproteins, composed of an alpha-subunit (INH-α) and one of two possible beta-subunits (ßA or ßB), with substantial roles in human reproduction and in endocrine-responsive tumours. Aims of this study were to determine the serological measurement of inhibin A (α-ßA) in breast cancer patients during chemotherapy. PATIENTS AND METHODS: A series of 30 breast cancer patients who underwent standardised chemotherapy were prospectively evaluated before chemotherapeutic treatment as well as four weeks after chemotherapy and two years after chemotherapy for the serological expression of inhibin A. For statistical analysis the Wilcoxon rank sum test was used for paired samples. Statistical significance was assumed at p<0.05. RESULTS: The concentration of inhibin A showed a significant decrease between data obtained before chemotherapy and after chemotherapy (p<0.005) and two-year follow-up (p<0.001). Interestingly, there were no differences in inhibin A concentrations between the four-week and two-year follow-up (p=0.744). DISCUSSION: Chemotherapy significantly decreases inhibin A concentration during chemotherapy. This might reflect a suppression of ovarian function, being also a marker for chemotherapy-induced amenorrhoea. Moreover, it has been suggested that inhibin A might be a tumour marker for breast cancer, and therefore a sudden increase in its concentration might be indicative of breast cancer recurrence.

Operator assessment of tractor roll angle with and without a tractor stability visual feedback device.

According to a 2004 National Institute for Occupational Safety and Health (NIOSH) report, approximately 250 to 350 fatalities occur each year due to incidents involving production agriculture workers and tractors. Tractor overturns account for about 150 to 200 of these deaths. The goals of this project were to study operators' understanding of tractor roll angles and test a device to effectively deliver stability information to the tractor operator. This project required the design and construction of a full-scale tractor cab roll simulator that was used to identify lateral roll angles at which volunteer participants felt uncomfortable, as well as lateral roll angles at which they would no longer operate a tractor. In addition, the participants performed a series of tasks to test the functionality of a visual slope indicator that was designed to help them estimate slope angles. The project tested 231 tractor operators' perceptions of safe operation on side slopes and 128 participants' interactions with the visual slope indicator. Testing showed that the visual slope indicator was able to influence the angle estimations of the novice tractor operator population and helped the entire population of participants more accurately rank the simulator scenarios.

Moment coefficients of skewness in the femoral neck cortical bone distribution of BAR 1002'00.

The cortical bone distributions in the femoral necks of apes and humans differ as a result of different loading environments caused by the realignment of the hip abductor apparatus. Femoral neck cortical bone in extant humans is very thin superiorly and thicker inferiorly, while the cortical bone in apes tends to be more uniformly thick. The unique internal anatomy of extant humans allows inferences to be made about primary locomotor function from incomplete femora. Here the differences in cortical bone distributions are quantified using moment coefficient of skewness. Skewness coefficients at two locations along the neck of the 6 million years old African femoral specimen BAR 1002'00 were compared to samples of 9 extant adult humans and 10 adult chimpanzees. The skewness coefficients of cortical bone in the femoral neck of BAR 1002'00 are more similar to those of chimpanzees than to humans, although the contrast is less pronounced in the region closer to the neck-shaft junction than more proximally toward the femoral head; this pattern indicates that in at least one respect this specimen attributed to Orrorin tugenensis manifests structural features suggesting influences of a hip abductor apparatus that had not yet evolved to the same extent as in extant humans.