Considering milk price volatility for investment decisions on the farm level after European milk quota abolition.

After the abolition of the milk quota in the European Union, milk price volatility is expected to increase because of the liberalized market conditions. At the same time, investment appraisal methods have not been updated to capture the increased uncertainty. Therefore, the objective of this paper is to assess the effect of changing price volatility due to quota abolition on investment decisions at the dairy farm level. To contribute to the objective and to approximate milk price volatility after the European milk quota abolition, the risk-adjusted discount rate for risk-averse dairy farmers is derived based on the milk price volatility of a milk price series from New Zealand. New Zealand dairy farmers have faced liberalized market conditions for more than 3 decades. Afterward, the risk-adjusted discount rate is applied to appraise milking technology investments for an average German dairy farmer. The results show that it is still more reasonable to invest in a parlor system than an automated milking system, although the net present value of the parlor system investment varies between €191,723 for risk-neutral dairy farmers and €100,094 for modestly risk-averse dairy farmers. For the automated milking system investment, the same calculations lead to €132,702 for risk-neutral dairy farmers and €31,635 for risk-averse dairy farmers. According to higher levels of milk price volatility after milk quota abolition, the reduction of the expected utility of the underlying investment decision for modest risk-averse dairy farmers is almost similar to a milk price decrease of 5% for risk-neutral dairy farmers. Therefore, the findings urge finance providers and extension services to consider the change of increasing milk price volatility after dairy quota abolition when giving dairy farmers financial advice. The risk-adjusted discount rate is a flexible tool to do so.

Heterozygosity for lysosomal acid lipase E8SJM mutation and serum lipid concentrations.

BACKGROUND AND AIM: The complete absence of the lysosomal acid lipase (LAL) enzyme function causes Wolman's Disease that is fatal within the first six months of life. Subtotal defects cause Cholesteryl ester storage disease (CESD), an autosomal recessive disorder leading to hepatic steatosis, fibrosis, micronodular cirrhosis, combined hyperlipidemia with low HDL-cholesterol, increased risk for atherosclerosis, premature death. Since the frequency of the Exon 8 splice junction mutation (c.894 G > A, E8SJM), the CESD leading mutation, is not rare in the general population (allele frequency 0.0025), we investigated the impact of this mutation on serum lipid profile in E8SJM carriers. METHODS AND RESULTS: We collected E8SJM carriers both form genetic study-population analysis and from Outpatient Lipid Clinics and then we assessed their serum lipid profile. We found thirteen individuals heterozygote for E8SJM. Most of them were Germans, three Spanish and two Italian. We found a significant increase in total cholesterol levels in both sexes with E8SJM mutation, leading to a significant increase in LDL cholesterol in males. CONCLUSIONS: Our results show that LAL E8SJM carriers have an alteration in lipid profile with a Polygenic Hypercholesterolemia phenotype, leading to an increase in cardiovascular risk profile.

Leptin and endocrine parameters in marathon runners.

Endurance training may lead to different hormonal alterations e. g., exercised induced hypothalamic ovarian/testicular dysfunction. The aim of this study was to reveal new connections between physical exercise, leptin and hormonal responses. 36 male participants of the Berlin-Marathon had their blood samples taken 2 days before the marathon. Hormones of the hypothalamic-pituitary axis and leptin were correlated with the training status and the achieved marathon time. Leptin correlated with the achieved marathon time after being adjusted for age and BMI (r=0.607, p<0.001) and was lowest in the best trained runners. Additionally, when the group was divided into quartiles of their achieved marathon time, significantly increased cortisol, fT4, cortisol/DHEAS ratio and decreased IGF-1 levels were observed in the slowest group. In the better trained group, a decrease of testosterone/DHT ratio and an increase of testosterone/cortisol ratio were observed. Our study supports the thesis of a linear relationship between physical fitness and leptin variations in the physiological range. We found an increased anabolic hormonal response in well trained marathon runners and hormonal reactions of increased stress in less trained runners. As the stress-induced neuroendocrine adaptations in our study group are associated with more higher leptin values, the pathophysiological role of decreased leptin values seems to be limited to overtrained athletes.

[The population-based mammography screening programme in Germany: uptake and first experiences of women in 10 federal states]. / Das populationsbezogene Mammografie-Screening-Programm in Deutschland: Inanspruchnahme und erste Erfahrungen von Frauen in 10 Bundesländern.

PURPOSE: Within the statutory health insurance (SHI) cancer early detection programme (KFU) an organised, population-based, quality-assured mammographic screening programme in Germany was initiated for women aged 50-69 years in 2004. The aim of the study was to evaluate uptake and first experiences of participants with this new screening approach and to evaluate the background of knowledge, attitudes and intention to address a needs-assessed communication strategy. MATERIALS AND METHODS: A representative, explorative survey within the female population was conducted in 10 federal states. A telephone survey of randomly selected 68,188 contacts was performed, 9,004 women gave informed consent to evaluate rates of invitation and uptake followed by a mailed questionnaire. Of these, 3,469 were returned and 3,226 were analysed. RESULTS: The invitation rate of the programme was 56.6%, the uptake of mammographic screening was 66%, and the screening coverage rate was 37.3%. 90% of the participants were insured by SHI, women with lower socio-economic strata were attracted in accordance with the data of the general population. 61% of all women did not know that the risk of breast cancer increases with age and 56% believed that screening prevents breast cancer. 62.1% judged their own risk to be low. A physician's recommendation to participate was significantly associated with attendance (p<0.05). 90% of the participants would follow the next invitation. CONCLUSION: The KFU targeted group of women was reached and the organised mammography screening programme was well perceived by invited women. For developing a lasting communication strategy information deficits have to be considered along with beliefs and attitudes of elegible women.

Age and sex as predictors of biochemical activity in acromegaly: analysis of 1485 patients from the German Acromegaly Register.

OBJECTIVE: We evaluated the German Acromegaly Register for clinical variables associated with the initial biochemical activity of patients with acromegaly. DESIGN: Retrospective analysis of data in the registry. PATIENTS: A total of 1485 patients with acromegaly (males 45.6%, females 54.4%) were treated in 42 German endocrine centres until November 2005. Linear regression models were used to estimate the influence of various parameters on biochemical activity. RESULTS: Male patients with acromegaly were significantly younger at the time of diagnosis than female patients (41 vs. 47 years, P < 0.0001) and had significantly higher random GH levels than females (21 vs. 14 ng/ml, P < 0.005) and IGF-1 levels (773 vs. 679 ng/ml, P < 0.0001), respectively. Age at initial presentation turned out to be the most important independent risk factor associated with random GH levels, oral glucose tolerance test-suppressed GH levels, IGF-1 levels, body mass index (BMI), tumour size and prevalence of hypopituitarism. Sex was an independent risk factor for IGF-1 levels, BMI and prevalence of hypopituitarism. Tumour size was an independent risk factor for both GH and IGF-1 levels. CONCLUSIONS: In summary, initial biochemical activity of acromegaly is influenced by patient's age and to a lesser degree by patient's sex. Male patients are on an average 6 years younger than females.

The thymus-adrenal connection: thymosin has corticotropin-releasing activity in primates.

Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.

Effects of repeated gram-positive and gram-negative clinical mastitis episodes on milk yield loss in Holstein dairy cows.

The objective of this study was to estimate the effects of recurrent episodes of gram-positive and gram-negative cases of clinical mastitis (CM) on milk production in Holstein dairy cows. We were interested in the severity of repeated cases in general, but also in the severity of the host response as judged by milk production loss when a previous case was caused by a similar or different microorganism. The results were based on data from 7,721 primiparous lactations and 13,566 multiparous lactations in 7 large dairy herds in New York State. The distribution of organisms in the CM cases showed 28.5% gram-positive cases, 31.8% gram-negative cases, 15.0% others, and 24.8% with no organism identified. Mixed models, with a random herd effect and an autoregressive covariance structure to account for repeated measurements, were used to quantify the effect of repeated CM and several other control variables (parity, week of lactation, other diseases) on milk yield. Our data indicated that repeated CM cases showed a very similar milk loss compared with the first case. No reduction of severity was present with increasing count of the CM case. Gram-negative cases had more severe milk loss compared with gram-positive and other cases irrespective of the count of the case in lactation. Milk loss in multipara (primipara) due to gram-negative CM was approximately 304 kg (228 kg) in the 50 d following CM. This loss was approximately 128 kg (133 kg) for gram-positive cases and 92 kg (112 kg) for other cases. The severity of a second case of gram-negative CM was not reduced by previous cases of gram-negative CM in multipara and only slightly less severe in a similar scenario in primipara cows. Similarly, a previous gram-positive case did not reduce severity of a second or third gram-positive case. Hence, our data do not support that immunological memory of previous exposure to an organism in the same generic class provides protection for a next case of CM with an organism in the same class.

Intravenous lipid and heparin infusion-induced elevation in free fatty acids and triglycerides modifies circulating androgen levels in women: a randomized, controlled trial.

BACKGROUND: The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. OBJECTIVE: The objective of the study was to analyze the effects of iv lipid and heparin infusion on circulating androgen levels in healthy women. DESIGN: This was a randomized, controlled, crossover trial. SETTING: The study was conducted at an endocrinology center. PATIENTS: Patients included 12 healthy young women during the early follicular phase of two subsequent cycles. INTERVENTION: After an overnight fast, a 20% lipid/heparin or a saline/heparin infusion was administered in random order for 330 min. MAIN OUTCOME MEASURES: A detailed characterization of androgen metabolism was performed. RESULTS: Elevations in free fatty acids and triglycerides, induced by lipid/heparin infusion, elevates the levels of androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone, 5alpha-dihydrotestosterone, estrone, and 17beta-estradiol. Urinary excretion of DHEA, DHEAS, 5-androstene-3beta,17beta-diol, and the sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 5-androstene-3beta,16alpha,17beta-triol, were reduced. CONCLUSION: The mechanism of iv lipid and heparin infusion-induced elevation of circulating androgens described here might contribute to the development of hyperandrogenism in women with PCOS and suggests that lowering of hyperlipidemia might be a potential therapeutic target in patients with PCOS to treat hyperandrogenemia.

Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids.

Glucocorticoids play an essential role in maintaining basal and stress-related homeostasis, and lack of glucocorticoid action is incompatible with life in primates. Most known effects of glucocorticoids are mediated by the intracellular GR. The magnitude of a cell's response to glucocorticoids depends both on the hormone level it is exposed to and on its glucocorticoid sensitivity, i.e. the efficiency of GR-mediated signal transduction. In this review, we have summarized the multiple endogenous and exogenous factors that have been shown to be involved in this signaling cascade and, thus, to alter glucocorticoid sensitivity.

Cardiovascular risk assessment in the metabolic syndrome: results from the Prospective Cardiovascular Munster (PROCAM) Study.

OBJECTIVES: We aimed (1) to construct a modified PROCAM risk algorithm, which incorporates BMI/waist circumference in a model for predicting coronary events; (2) to evaluate how accurate this and the previously established PROCAM risk algorithm predict coronary risk in individuals with metabolic syndrome. DESIGN: Prospective Cardiovascular Münster (PROCAM) Study, a prospective study of men and women at work in the northwest of Germany. SUBJECTS: A total of 7134 men aged 35-65 years at study entry. MEASUREMENTS: On the basis of 404 major coronary events (defined as nonfatal MI and coronary deaths), which occurred within 10 years of follow-up, a modified PROCAM risk algorithm was constructed by incorporating BMI/waist circumference as fixed variable in a Cox proportional hazards model for predicting coronary events. The metabolic syndrome was defined according to the latest recommendations proposed by the NCEP-ATP III Panel. RESULTS: Men who were classified as having the metabolic syndrome (n=2325, prevalence: 32.6%) were 2.59-fold more likely to experience a major coronary event within 10 years of follow-up than men not having the metabolic syndrome. In men with metabolic syndrome, the observed major coronary event rate of 9.6% corresponded well with their estimated global risk according to the modified BMI-based PROCAM risk algorithm (10.2%). Comparative calculations performed with the previously published fully adjusted PROCAM algorithm yielded very similar results. CONCLUSION: Both PROCAM algorithms provide very accurate means to ascertain coronary risk in male patients with metabolic syndrome.

Effects of repeated episodes of generic clinical mastitis on mortality and culling in dairy cows.

Bovine clinical mastitis (CM) can be detrimental to a dairy farm's profitability, not only in terms of lost production and treatment costs, but also because of the loss of the cows themselves. Our objective was to estimate the effects of multiple occurrences of generic bovine CM on mortality and culling. We studied 16,145 lactations from 5 large, high-producing dairy herds, with 3,036 first, 758 second, and 288 third CM cases observed in the first 10 mo after calving. Generalized mixed models, with a random herd effect, were used to quantify the effect of CM on mortality and culling. Other control variables included in the models were parity, stage of lactation, and other diseases. Clinical mastitis in the current month significantly increased mortality in all parities. Among primipara, odds ratios and 95% confidence intervals were 5.6 (1.7, 18.0), 23.3 (7.1, 76.2), and 27.8 (3.7, 209.9) for the first, second, and third CM episode, respectively. Among multipara, respective estimates were 9.9 (7.4, 13.2), 12.0 (8.0, 18.0), and 11.5 (6.1, 21.4). Clinical mastitis significantly increased the risk of a cow being culled for a period of at least 2 mo after any CM case. Our findings provide dairy producers with information on mortality and culling associated with CM cases without considering the causative agent, and can also be used for economic analysis of CM management options.

The cost of generic clinical mastitis in dairy cows as estimated by using dynamic programming.

The objective of this study was to estimate the cost of generic clinical mastitis (CM) in high-yielding dairy cows given optimal decisions concerning handling of CM cases. A specially structured optimization and simulation model that included a detailed representation of repeated episodes of CM was used to study the effects of various factors on the cost of CM. The basic scenario was based on data from 5 large herds in New York State. In the basic scenario, 92% of the CM cases were recommended to be treated. The average cost of CM per cow and year in these herds was $71. The average cost of a CM case was $179. It was composed of $115 because of milk yield losses, $14 because of increased mortality, and $50 because of treatment-associated costs. The estimated cost of CM was highly dependent on cow traits: it was highest ($403) in cows with high expected future net returns (e.g., young, high-milk-yielding cows), and was lowest ($3) in cows that were recommended to be culled for reasons other than mastitis. The cost per case of CM was 18% higher with a 20% increase in milk price and 17% lower with a 20% decrease in milk price. The cost per case of CM was affected little by a 20% change in replacement cost or pregnancy rate. Changes in CM incidence, however, resulted from changes in these factors, thus affecting whole-farm profitability. The detailed results obtained from this insemination and replacement optimization model can assist farmers in making CM treatment decisions.

[Guideline for the Early Detection of Breast Cancer in Germany 2008. Recommendations from the short version]. / Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008 : Auszug aus der Kurzfassung: Handlungsempfehlungen.

The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

[Risk factor calculator for medical underwriting of life insurers based on the PROCAM study]. / Risikofaktorenrechner für die Risiko prüfung in der Lebensversicherung auf Basis der PROCAM Studie.

For its electronic manual GEM, used to perform medical risk assessment in life insurance, SCOR Global Life Germany has developed an innovative and evidence-based calculator of the mortality risk depending on cardiovascular risk factors. The calculator contains several new findings regarding medical underwriting, which were gained from the analysis of the PROCAM (Prospective Cardiovascular Münster) study. For instance, in the overall consideration of all risk factors of a medically examined applicant, BMI is not an independent risk factor. Further, given sufficient information, the total extra mortality of a person no longer results from adding up the ratings for the single risk factors. In fact, this new approach of risk assessment considers the interdependencies between the different risk factors. The new calculator is expected to improve risk selection and standard acceptances will probably increase.

Continuous administration of synthetic ovine corticotropin-releasing factor in man. Physiological and pathophysiological implications.

The continuous 24-h infusion of a maximally stimulating dose (1 micrograms/kg per h) of ovine corticotropin-releasing factor (CRF) in man caused a modest elevation of plasma cortisol (17.2 +/- 1.4 micrograms/dl) and urinary-free cortisol (173 +/- 43 micrograms/24 h) concentrations, which was far less than that seen with a maximally stimulating dose of ACTH (50.4 +/- 2.2 micrograms/dl and 1,200 +/- 94 micrograms/24 h, respectively). The circadian rhythms of plasma ACTH and cortisol were preserved during CRF administration. An intravenous bolus injection of 1 microgram/kg of ovine CRF given to normal volunteers under basal conditions resulted in elevated plasma ACTH and cortisol peak levels (28 +/- 6 pg/ml and 15.0 +/- 1.0 micrograms/dl, respectively). However, no plasma ACTH and cortisol responses were observed when an identical CRF stimulation test was given at the end of the continuous infusion. These findings suggest that the stimulatory activity of exogenous CRF on the ACTH-secreting cells of the pituitary gland is restrained by the negative feedback of cortisol. The persistent circadian rhythm of ACTH, despite a constant level of plasma CRF during the infusion, suggests that the circadian variation in the activity of the hypothalamic-pituitary-adrenal axis cannot be explained solely by circadian periodicity of the endogenous CRF stimulus.

Expression of urocortin in the extravillous human trophoblast at the implantation site.

Urocortin (UCN) is a 40 amino acid peptide which is closely related to corticotropin-releasing hormone and binds with high affinity to both CRH type 1 and type 2 receptors. UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta. This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin. For this reason, immunohistochemistry was performed on tissue sections from paraffin-embedded human first trimester placentas and freshly isolated human invasive extravillous trophoblast cells (EVT) were analyzed for UCN expression using RT-PCR and immunofluorescence. Finally, UCN promoter activity was analyzed in the JEG3 human choriocarcinoma cell line. Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells. Both UCN mRNA and peptide were detectable in freshly isolated EVT. Finally, a human UCN promoter luciferase reporter construct transfected into JEG3 cells was significantly inducible by phorbol ester plus ionomycin, but not by phorbol ester alone or by forskolin. Collectively, the present study reports the expression of UCN in EVT and the activation of the UCN gene promoter by the diacylglycerol/PKC pathway. The functional significance of urocortin for the physiology of EVT requires further investigation.

Treatment of hyperlipidemia in primary practise in Germany: sub-group analyses from the 4E-registry with particular emphasis on men and women with diabetes mellitus.

AIMS: To investigate the achievement of treatment goals for low density lipoprotein (LDL) cholesterol in men and women with diabetes mellitus receiving statins in a primary-care setting in Germany. METHODS: 6,827 men and 5,989 women with diabetes mellitus were recruited from among the 28,200 men and 24,200 women participating in the 4E registry of patients being treated with statins for primary hypercholesterolemia unresponsive to diet and lifestyle. Participants were assessed after 6 weeks and 9 months of statin therapy. Attainment of treatment targets was assessed (i) using individual LDL goals based on each participant's individual level of risk and (ii) based on the 2.6 mmol/L target recommended by current European and U.S. guidelines for persons with diabetes. RESULTS: At baseline, patients with and without diabetes mellitus had similar LDL cholesterol levels patients (men: 4.5+/-1 vs. 4.7+/-1 mmol/L, women: 4.7+/-1 vs. 4.9+/-1 mmol/L respectively). The mean drop in LDL cholesterol on statin therapy was similar in men and women with and without diabetes, ranging from 26-27 percent all subgroups. After 9 months of statins, individual LDL goals were achieved by 25% of men and 24% of women with diabetes, while only 16% of diabetic men and 12% of diabetic women achieved the 2.6 mmol/L LDL target. These success rates were similar to those of non-diabetics, including those at high risk, in 4E. CONCLUSIONS: Patients with diabetes mellitus in 4E responded just as well to statins as patients without diabetes. However, achievement of treatment goals in patients with diabetes was just as poor as in other high-risk groups in the 4E cohort.