Evaluation of laboratory and on-farm tests to estimate colostrum quality for dairy cows.

The objectives of this study were to evaluate different analytical methods to determine colostrum quality in dairy cattle, including one laboratory-based method (ELISA) and 4 on-farm tests. We hypothesized that the colostral IgG concentration using different analytical methods, such as ELISA (mg/mL), digital Brix refractometer (% Brix), colostrometer (specific gravity and mg/mL), an outflow funnel (seconds), and a lateral flow assay (mg/mL), were highly correlated with the reference method, radial immunodiffusion (RID; mg/mL) and would generate comparable results. Colostrum samples were collected from 209 Holstein Friesian cows on 2 commercial dairy farms in Germany. Colostrum weight and colostrum temperature were measured. Test characteristics, such as optimum thresholds, sensitivity, specificity, and area under the curve (AUC) were determined using a receiver operating characteristic curve analyses for each test. Out of 209 colostrum samples assessed by RID, 186 (89%) samples had high quality (≥50 mg IgG/mL), while 23 colostrum samples (11%) showed poor quality with IgG concentrations less than 50 mg/mL. The mean IgG concentration (±SD) was 101.3 ± 45.9 mg/mL and the range was 6.0 to 244.3 mg/mL. The Pearson correlation coefficient (r) between RID and ELISA was r = 0.78. In comparison to RID, Pearson correlation coefficients for the on-farm tests were: r = 0.79 (digital Brix refractometry), r = 0.58 (colostrometer: specific gravity), r = 0.61 (colostrometer: temperature corrected), r = 0.26 (outflow funnel) and r = 0.43 (lateral flow assay), respectively. The optimal threshold to identify high-quality colostrum using ELISA was 50.8 mg/mL with sensitivity 91.3%, specificity 92.3%, and AUC of 0.94. For the on-farm tests sensitivity ranged from 95.7% (Brix refractometry) to 60.9% (lateral flow assay). Specificity ranged from 88.6% (lateral flow assay) to 75.9% (colostrometer: temperature corrected). The AUC ranged from 0.93 (Brix refractometry) to 0.73 (outflow funnel). Based on the AUC, ELISA (0.94) and Brix refractometry (0.93) can be considered highly accurate. In conclusion, the ELISA is accurate to assess colostrum quality. Regarding the on-farm tests only the digital Brix refractometer and the colostrometer were adequate to determine colostrum quality.

The effect of transdermal flunixin meglumine on blood cortisol levels in dairy calves after cautery disbudding with local anesthesia.

The objective of this study was to evaluate the effect of the nonsteroidal anti-inflammatory drug transdermal flunixin meglumine (Finadyne Transdermal) on plasma cortisol, average daily weight gain, and standing and lying behavior of calves, when given at the time of disbudding combined with local anesthesia. A sedative was not used to minimize pharmacological interactions. Seventy-one female Holstein Friesian calves aged 13 ± 2 d, with an average weight of 48.9 ± 4.26 kg were enrolled in the study. All calves were randomly assigned to one of 3 treatment groups: (1) control group (CON, n = 27), (2) 1-flunixin group (1-FLU, n = 26) with a single administration of transdermal flunixin meglumine at disbudding, and (3) 2-flunixin group (2-FLU, n = 24) with 2 administrations of transdermal flunixin meglumine, the first treatment at disbudding and the second 6 h after disbudding. Although the CON group received a placebo, 1-FLU and 2-FLU received flunixin meglumine transdermally. To account for plasma cortisol changes due to manipulation and handling of the calves, a sham disbudding procedure was performed one week before disbudding took place. Sham disbudding was conducted by using a cold cautery dehorner applied to each horn bud for 10 s. Disbudding was performed in a similar way by using a hot cautery dehorner. Plasma samples were collected to measure the stress biomarker cortisol at 7 different time points. Body weights were measured 4 times in 2 wk. Standing and lying behavior was assessed via 3-dimensional accelerometer. During sham disbudding and disbudding mean plasma cortisol concentrations were 6.09 ± 2.5 ng/mL and 5.16 ± 2.8 ng/mL, respectively. Treatment tended to have an effect on plasma cortisol concentrations during sham disbudding and had an effect on plasma cortisol concentrations during disbudding. Plasma cortisol concentrations were affected by treatment 2 h after disbudding in comparison to CON group. Furthermore, there was a significant effect on plasma cortisol concentrations 6 h after disbudding in contrast to CON. A return to baseline plasma cortisol levels (initial concentrations) was not achieved in CON during disbudding. There was no statistical difference between average daily weight gain and the treatment procedure. Total lying time was not affected by treatment after disbudding. In conclusion, transdermal flunixin meglumine given at the time of disbudding combined with local anesthesia decreased concentrations of the stress biomarker cortisol, but a second dose 6 h after disbudding had no further effect on plasma cortisol levels.

Active Surveillance Versus Radical Prostatectomy in Favorable-risk Localized Prostate Cancer.

BACKGROUND: Active surveillance (AS) and radical prostatectomy (RP) are both accepted treatments for men with favorable-risk localized prostate cancer (PCa) (ie, clinical tumor category 1-2b, Gleason Grade Group 1-2, and prostate-specific antigen < 20 ng/mL). However, head-to-head studies comparing oncologic outcomes and survival between these 2 treatment strategies are warranted. The objective of this study was to compare the use of prostate cancer treatments and PCa death in men managed on AS and men who underwent immediate RP. PATIENTS AND METHODS: This was an observational study including 647 men on AS and 647 men treated with RP propensity score matched. We examined the 10-year cumulative incidence of salvage radiotherapy, hormonal therapy, castration-resistant PCa, and PCa death. RESULTS: The 10-year curative treatment-free survival for men on AS was 61% (95% confidence interval [CI], 57%-65%). No differences in use of salvage radiotherapy (AS, 2.7%; 95% CI, 1.4%-4.1% vs. RP 5.4%; 95% CI, 3.4%-7.3%), hormonal therapy (AS, 6.9%; 95% CI, 4.4%-9.4% vs. RP, 4.1%; 95% CI, 2.5%-5.6%), developing castration-resistant PCa (AS, 1.7%; 95% CI, 0.5%-2.9% vs. RP, 2.0%; 95% CI, 0.7%-3.4%), or cumulative PCa mortality (AS, 0.4%; 95% CI, 0%-1.0% vs. RP, 0.5%; 95% CI, 0%-1.5%) were observed between the treatment strategies. The main limitation was the non-random allocation to treatment strategy. CONCLUSION: In this observational study on men with favorable-risk localized PCa, we found similar PCa mortality at 10 years between men on AS and men who underwent immediate RP. Moreover, there were no differences in the use of PCa therapies between the groups. Our study supports active surveillance as a treatment strategy for men with favorable-risk localized PCa.

Palliative Prostate Artery Embolization for Prostate Cancer: A Case Series.

INTRODUCTION: Prostate artery embolization (PAE) is recognized as a treatment for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia. LUTS and urinary retention are common in men with prostate cancer (PCa). The purpose of this study was to estimate the efficacy and safety of palliative PAE on LUTS or urinary retention in men with advanced PCa. MATERIALS AND METHODS: This prospective, single-center trial was conducted from March 2017 to November 2018. The trial protocol was registered online (ClinicalTrials.gov Identifier: NCT03104907). Only men with advanced PCa suffering from LUTS or urinary retention were included. The primary outcome was the ability to void without a catheter and International Prostate Symptom Score (IPSS) in non-catheter-dependent patients. The paired t test was used to analyze changes from baseline with 95% confidence intervals (CI). A p value < 0.05 was considered statistically significant. RESULTS: Seventeen patients were assessed for eligibility, and 15 patients with a mean age of 73.8 years were enrolled. Four men did not complete follow-up: cancer-related death (n = 2), lost to follow-up (n = 1), and unsuccessful embolization due to severe atherosclerosis (n = 1). Bilateral embolization was achieved in ten cases, and urinary retention resolved in one of six patients. LUTS improved in the remaining (n = 5) patients by a mean 12.2-point reduction in IPSS (95% CI - 23.53; - 0.87). According to the CIRSE classification, two grade 1 and two grade 3 complications occurred. CONCLUSION: In this study, palliative PAE was safe and efficient for treatment for LUTS associated with PCa. LEVEL OF EVIDENCE: Level 4, Case Series. Trial registration ClinicalTrials.gov Identifier: NCT03104907.

Management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care is noninferior to management in a specialized outpatient clinic: a randomized, noninferiority trial.

AIM: To evaluate whether management of people with Type 2 diabetes shared between a specialized outpatient clinic and primary health care has noninferior HbA1c outcomes compared with mono-sectorial management in a specialized outpatient clinic. METHODS: A randomized controlled, noninferiority study. People with moderate hyperglycaemia, hypertension and/or incipient complications were eligible for the study. All participants had annual comprehensive check-ups at the outpatient clinic. Quarterly check-ups were conducted by general practitioners (GPs) for the shared care group and by endocrinologists at the outpatient clinic for the control group. The primary outcome was the mean difference in HbA1c from baseline to 12 months of follow-up. The noninferiority margin for HbA1c was 4.4 mmol/mol. RESULTS: A total of 140 people were randomized [age 65.0 ± 0.9 years, HbA1c 52 ± 0.8 mmol/mol (6.9 ± 0.1%), systolic BP 135.6 ± 1.1 mmHg; all mean ± sem]. Peripheral neuropathy was present in 68% of participants and microalbuminuria in 19%; 15% had history of a previous major cardiovascular event. Among study completers (n = 133), HbA1c increased by 2.3 mmol/mol (0.2%) in the shared care group and by 1.0 mmol/mol (0.1%) in the control group, with a between-group difference of 1.3 mmol/mol [90% confidence interval (CI) -1.3, 3.9] (0.1%, 90% CI -0.1, 0.4). Noninferiority was confirmed in both per protocol and intention to treat analyses. CONCLUSION: We found that our shared care programme was noninferior to specialized outpatient management in maintaining glycaemic control in this group of people with Type 2 diabetes. Shared care should be considered for the future diabetes management of Type 2 diabetes.

Prostate artery embolisation for benign prostatic hyperplasia: a systematic review and meta-analysis.

OBJECTIVES: Prostate artery embolisation (PAE) is a new minimally invasive treatment for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). The purpose of this study was to review the efficacy and safety of PAE in the treatment of BPH with LUTS. METHODS: A systematic review performed according to the PRISMA guidelines with a pre-specified search strategy for PubMed, Web of Science, Cochrane Library and Embase databases protocol (PROSPERO ID: CRD42017059196). Trials studying the efficacy of prostate artery embolisation to treat LUTS with more than ten participants and follow-up longer than 6 months were included by two independent authors. Outcomes investigated were International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate-specific antigen (PSA), peak void flow (Qmax), post-void residual (PVR) and complications. To summarise mean change from baseline, a meta-analysis was done using the random-effects model. RESULTS: The search returned 210 references, of which 13 studies met the inclusion criteria, representing 1,254 patients. Patients in the included studies with data available for meta-analysis had moderate to severe LUTS and a mean IPSS of 23.5. Statistically significant (p value < 0.05) improvements of all investigated outcomes were seen at 12-month follow-up. Major complications were reported in 0.3% of the cases. CONCLUSIONS: Our findings suggest that PAE can reduce moderate to severe LUTS in men with BPH with a low risk of complications. KEY POINTS: • Prostate artery embolisation (PAE) improved International Prostate Symptom Score (IPSS) by 67%. • Major complications after PAE are very rare. • Use of cone-beam CT may reduce risk of non-target embolisation.

Methodology for the investigation of ignition near hot surfaces in a high-pressure shock tube.

Autoignition of fuel/air mixtures is a determining process in internal combustion engines. Ignition can start either homogeneously in the gas phase after compression or in the vicinity of hot surfaces. While ignition properties of commercial fuels are conventionally described by a single quantity (octane number), it is known that some fuels have a varying propensity to the two processes. We present a new experimental concept that generates well-controlled temperature inhomogeneities in the shock-heated gases of a high-pressure shock tube. A shock-heated reactive mixture is brought into contact with a heated silicon nitride ceramic glow plug. The glow-plug temperature can be set up to 1200 K, higher than the post-reflected-shock gas temperatures (650-1050 K). High-repetition-rate chemiluminescence imaging is used to localize the onset of ignition in the vicinity of the hot surface. In experiments with ethanol, the results show that in most cases under shock-heated conditions, the ignition begins inhomogeneously in the vicinity of the glow plug and is favored because of the high wall temperature. Additionally, the interaction of geometry, external heating, and gas-dynamic effects was investigated by numerical simulations of the shock wave in a non-reactive flow.

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts.

OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10-16). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa.

Risk of prostate cancer diagnosis and mortality in men with a benign initial transrectal ultrasound-guided biopsy set: a population-based study.

BACKGROUND: The risk of missing prostate cancer in the transrectal ultrasound-guided systematic biopsies of the prostate in men with suspected prostate cancer is a key problem in urological oncology. Repeat biopsy or MRI-guided biopsies have been suggested to increase sensitivity for diagnosis of prostate cancer, but the risk of disease-specific mortality in men who present with raised prostate-specific antigen (PSA) concentration and a benign initial biopsy result remains unknown. We investigated the risk of overall and prostate cancer-specific mortality in men with a benign initial biopsy set. METHODS: Data were extracted from the Danish Prostate Cancer Registry-a population-based registry including all men undergoing histopathological assessment of prostate tissue. All men who were referred for transrectal ultrasound-guided biopsy for assessment of suspected prostate cancer between Jan 1, 1995, and Dec 31, 2011, in Denmark were eligible for inclusion. Follow-up data were obtained on April 28, 2015. The primary endpoint was the cumulative incidence of prostate cancer-specific mortality, analysed in a competing risk setting, with death from other causes as the competing event. FINDINGS: Between Jan 1, 1995, and Dec 31, 2011, 64 430 men were referred for transrectal ultrasound-guided biopsy, of whom 63 454 were eligible for inclusion. Median follow-up was 5·9 years (IQR 3·8-8·5) and the total follow-up time, from the enrolment of the first patient on Jan 1, 1995, until the extraction of causes of death on April 28, 2015, was 20 years. 10 407 (30%) of 35 159 men with malignant initial biopsy sets died from prostate cancer, compared with 541 (2%) of 27 181 men with benign initial biopsy sets. Estimated overall 20-year mortality was 76·1% (95% CI 73·0-79·2). In all men referred for transrectal ultrasound-guided biopsy, the cumulative incidence of prostate cancer-specific mortality after 20 years was 25·6% (24·7-26·5) versus 50·5% (47·5-53·5) for mortality from other causes. In men with benign initial biopsy sets, the cumulative incidence of prostate cancer-specific mortality was 5·2% (3·9-6·5) versus 59·9% (55·2-64·6) for mortality from other causes. In men with PSA concentrations 10 µg/L or lower and benign initial biopsy sets (2779 men), the cumulative incidence of prostate cancer-specific mortality was 0·7% (0·2-1·3). Cumulative incidence of prostate cancer specific mortality in men with benign initial biopsy sets was 3·6% (95% CI 0·1-7·2) for men with a PSA higher than 10 ng/mL but 20 ng/mL or less (855 men) and 17·6% (12·7-22·4) and for men with a PSA higher than 20 ng/mL (454 men). INTERPRETATION: The first systematic transrectal ultrasound-guided biopsy set holds important prognostic information. The 20-year risk of prostate cancer-specific mortality in men with benign initial results is low. Our findings question whether men with low PSA concentration and a benign initial biopsy set should undergo further diagnostic assessment in view of the high risk of mortality from other causes. FUNDING: Capital Region of Denmark's Fund for Health Research, Danish Cancer Society, Danish Association for Cancer Research, and Krista and Viggo Petersen's Foundation.

Danish Prostate Cancer Registry - methodology and early results from a novel national database.

BACKGROUND: Systematized Nomenclature of Medicine (SNOMED) codes are computer-processable medical terms used to describe histopathological evaluations. SNOMED codes are not readily usable for analysis. We invented an algorithm that converts prostate SNOMED codes into an analyzable format. We present the methodology and early results from a new national Danish prostate database containing clinical data from all males who had evaluation of prostate tissue from 1995 to 2011. MATERIALS AND METHODS: SNOMED codes were retrieved from the Danish Pathology Register. A total of 26,295 combinations of SNOMED codes were identified. A computer algorithm was developed to transcode SNOMED codes into an analyzable format including procedure (eg, biopsy, transurethral resection, etc), diagnosis, and date of diagnosis. For validation, ~55,000 pathological reports were manually reviewed. Prostate-specific antigen, vital status, causes of death, and tumor-node-metastasis classification were integrated from national registries. RESULTS: Of the 161,525 specimens from 113,801 males identified, 83,379 (51.6%) were sets of prostate biopsies, 56,118 (34.7%) were transurethral/transvesical resections of the prostate (TUR-Ps), and the remaining 22,028 (13.6%) specimens were derived from radical prostatectomies, bladder interventions, etc. A total of 48,078 (42.2%) males had histopathologically verified prostate cancer, and of these, 78.8% and 16.8% were diagnosed on prostate biopsies and TUR-Ps, respectively. FUTURE PERSPECTIVES: A validated algorithm was successfully developed to convert complex prostate SNOMED codes into clinical useful data. A unique database, including males with both normal and cancerous histopathological data, was created to form the most comprehensive national prostate database to date. Potentially, our algorithm can be used for conversion of other SNOMED data and is available upon request.

Severe hypoglycaemia during treatment with sulphonylureas in patients with type 2 diabetes in the Capital Region of Denmark.

AIMS: Sulphonylureas (SU) are currently recommended as a well-established second line treatment in guidelines for type 2 diabetes (T2DM). In the Capital Region of Denmark 16,865 patients were given SU as part of their treatment of T2DM in 2010-2011. To what extent SU are associated with hospitalizations due to severe hypoglycaemic episodes, defined as episodes with a need for external assistance, was investigated. The prevalence and characteristics of these patients and potential risk factors were studied. METHODS: ICD-10 diagnosis codes were used to identify patients hospitalized due to hypoglycaemia and T2DM for a period of 2 years (2010-2011). Inclusion criteria were T2DM, hospitalization due to hypoglycaemia and treatment with SU as monotherapy or in combination with other glucose-lowering drugs except insulin treatment. RESULTS: We identified 161 patients fulfilling the inclusion criteria. Their mean age was 76 (53-97) years and 54% were males. Sixty percent of the patients had diabetic complications, including 19% with diabetic nephropathy. The major reason for severe hypoglycaemia was an unchanged dose of SU despite of a significant decline in food intake (45%). In 22% of the patients more than one reason was listed, most commonly a concomitant infection associated with decreased food intake and unchanged dose of SU. CONCLUSION: The incidence of hospital admission-requiring severe hypoglycaemia in patients treated with SU was 0.48 episodes per 100 patient-years of SU-treated patients. It was mainly older patients with diminished food intake, excessive alcohol use or other medications, concomitant infection, and with diabetic complications.

[Social Security Needs Social Medicine: Self-image of Physicians Practicing Social Medicine in Statutory Health Insurances and Social Security Systems]. / Soziale Sicherheit braucht Sozialmedizin Selbstverständnis von Ärztinnen und Ärzten in der sozialmedizinischen Begutachtung und Beratung.

OBJECTIVE: In January, 2014, the division "Social Medicine in Practice and Rehabilitation" of the German Society for Social Medicine and Prevention established a working group on the self-image of the physicians active in the field of social medicine (medical expertise and counseling). METHODS: The result of this work is the contribution presented here after consensus was achieved by specialists of social medicine from different fields and institutions (social security etc.) and in good cooperation with Prof. Dr. Gostomzyk and Prof. Dr. Robra. RESULTS: Based on the importance of an up to date social medicine for claimants and recipients of benefits on the one hand and the social security system on the other, and also on a description of the subjects, objectives and methods the following aspects are presented: · The perspective of social medicine. · Qualification in social medicine, concerning specialist training and continuing medical education. · The fields of duty of experts in social medicine. · The proceedings in social medicine. The working group identified challenges for the specialists in social medicine by a narrowed perception of social medicine by physicians in hospitals and practice, accompanied by an enlarged importance of expertise in social medicine, by the demand for more "patient orientation" and gain of transparency, and concerning the scientific foundation of social medicine. CONCLUSIONS: The working group postulates: · The perspective of social medicine should be spread more widely.. · Confidence in experts of social medicine and their independency should be strengthened.. · The not case-related consulting of the staff and executives should be expanded.. · Social medicine in practice needs support by politics and society, and especially by research and teaching.. · Good cooperation and transfer of experiences of the different branches of social security are essential for the impact of social medicine..

ERG protein expression over time: from diagnostic biopsies to radical prostatectomy specimens in clinically localised prostate cancer.

AIMS: We evaluated the consistency in ERG protein expression from diagnostic specimens through rebiopsies to radical prostatectomies in patients with clinically localised prostate cancer to investigate the validity of ERG status in biopsies. METHODS: ERG expression was assessed by immunohistochemistry (IHC) in 625 biopsy sets and 86 radical prostatectomy specimens from 265 patients with prostate cancer managed on active surveillance. For IHC, a rabbit monoclonal primary antibody was used (clone: EPR3864). TMPRSS2-ERG fluorescence in situ hybridisation (FISH) analyses were performed in 74 biopsies using the FISH ZytoLight TriCheck Probe (SPEC ERG/TMPRSS2). FISH results were correlated with IHC findings. RESULTS: The concordance between FISH and IHC was 97.3% and IHC demonstrated a sensitivity and specificity for ERG rearrangement of 100% and 95.5%, respectively. Applying IHC, 38.1% of patients were ERG-positive, 53.6% were ERG-negative and 8.3% showed both ERG-positive and negative tumour foci (ERG heterogeneous) at diagnosis. When ERG status was dichotomised (ERG-positive or heterogeneous vs ERG-negative), 95.6%-97.1% of patients did not experience ERG reclassification during the first two rounds of rebiopsies. The concordance in ERG status between biopsies and surgical specimen was 89.5%-94.2% depending on the number of rebiopsies included. Sampling bias was assumed to explain most (81.3%) of the mismatches in ERG status. CONCLUSIONS: Consistency in ERG status ranged from 90% to 95% for patients undergoing serial biopsies and radical prostatectomy. This indicates that biopsies can be used reliably to investigate ERG's prognostic and predictive value.

Potential and limits to unravel the genetic architecture and predict the variation of Fusarium head blight resistance in European winter wheat (Triticum aestivum L.).

Genome-wide mapping approaches in diverse populations are powerful tools to unravel the genetic architecture of complex traits. The main goals of our study were to investigate the potential and limits to unravel the genetic architecture and to identify the factors determining the accuracy of prediction of the genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) based on data collected with a diverse panel of 372 European varieties. The wheat lines were phenotyped in multi-location field trials for FHB resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide association mapping in combination with fivefold cross-validations and observed surprisingly high accuracies of prediction for marker-assisted selection based on the detected quantitative trait loci (QTLs). Using a random sample of markers not selected for marker-trait associations revealed only a slight decrease in prediction accuracy compared with marker-based selection exploiting the QTL information. The same picture was confirmed in a simulation study, suggesting that relatedness is a main driver of the accuracy of prediction in marker-assisted selection of FHB resistance. When the accuracy of prediction of three genomic selection models was contrasted for the three marker data sets, no significant differences in accuracies among marker platforms and genomic selection models were observed. Marker density impacted the accuracy of prediction only marginally. Consequently, genomic selection of FHB resistance can be implemented most cost-efficiently based on low- to medium-density SNP arrays.

Active surveillance for localized prostate cancer: an analysis of patient contacts and utilization of healthcare resources.

OBJECTIVE: Evidence supports active surveillance (AS) as a means to reduce overtreatment of low-risk prostate cancer (PCa). The consequences of close and long-standing follow-up with regard to outpatient visits, tests and repeated biopsies are widely unknown. This study investigated the trajectory and costs of AS in patients with localized PCa. MATERIALS AND METHODS: In total, 317 PCa patients were followed in a prospective, single-arm AS cohort. The primary outcomes were number of patient contacts, prostate-specific antigen (PSA) tests, biopsies, hospital admissions due to biopsy complications and patients eventually undergoing curative treatment. The secondary outcome was cost. RESULTS: The 5 year cumulative incidence of discontinued AS in a competing-risk model was 40%. During the first 5 years of AS patients underwent a median of two biopsy sets, and patients were seen in an outpatient clinic including PSA testing three to four times annually. In total, 38 of the 406 biopsy sessions led to hospital admission and 87 of the 317 patients required treatment for bladder outlet obstruction (BOO). With a median of 3.7 years' follow-up, the total cost of AS was euro (€) 1,240,286. Assuming all patients had otherwise undergone primary radical prostatectomy, the cost difference favoured AS with a net benefit of €662,661 (35% reduction). CONCLUSIONS: AS entails a close clinical follow-up with a considerable risk of rebiopsy complication, treatment of BOO and subsequent delayed definitive therapy. This risk should be weighed against a potential economic benefit and reduction in the risk of overtreatment compared to immediate radical treatment.

Active surveillance for clinically localized prostate cancer--a systematic review.

Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS strategy and how they should be managed within the program. However, uncertainties persists concerning optimal patient selection and reliable progression criteria, as well as the long-term safety of AS.

ERG protein expression in diagnostic specimens is associated with increased risk of progression during active surveillance for prostate cancer.

BACKGROUND: Compelling biomarkers identifying prostate cancer patients with a high risk of progression during active surveillance (AS) are needed. OBJECTIVE: To examine the association between ERG expression at diagnosis and the risk of progression during AS. DESIGN, SETTING, AND PARTICIPANTS: This study included 265 patients followed on AS with prostate-specific antigen (PSA) measurements, clinical examinations, and 10-12 core rebiopsies from 2002 to 2012 in a prospectively maintained database. ERG immunohistochemical staining was performed on diagnostic paraffin-embedded formalin-fixed sections with a ready-to-use kit (anti-ERG, EPR3864). Men were characterised as ERG positive if a minimum of one tumour focus demonstrated ERG expression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall AS progression was defined as clinical progression: increased clinical tumour category ≥cT2b by digital rectal examination and ultrasound, and/or histopathologic progression: upgrade of Gleason score, more than three positive cores or bilateral positive cores, and/or PSA progression: PSA doubling time <3 yr. Risk of progression was analysed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method). Curatively intended treatment, watchful waiting, and death without progression were treated as competing events. RESULTS AND LIMITATIONS: A total of 121 of 142 ERG-negative and 96 of 123 ERG-positive patients had complete diagnostic information. In competing risk models, the ERG-positive group showed significantly higher incidences of overall AS progression (p<0.0001) and of the subgroups PSA progression (p<0.0001) and histopathologic progression (p<0.0001). The 2-yr cumulative incidence of overall AS progression was 21.7% (95% confidence interval [CI], 14.3-29.1) in the ERG-negative group compared with 58.6% (95% CI, 48.7-68.5) in the ERG-positive group. ERG positivity was a significant predictor of overall AS progression in multiple Cox regression (hazard ratio: 2.45; 95% CI, 1.62-3.72; p<0.0001). The main limitation of this study is its observational nature. CONCLUSIONS: In our study, ERG positivity at diagnosis can be used to estimate the risk of progression during AS. If confirmed, ERG status can be used to individualise AS programmes. PATIENT SUMMARY: The tissue biomarker ERG identifies active surveillance patients with an increased risk of disease progression.

Nuclear deformation and neutron excess as competing effects for dipole strength in the pygmy region.

The electromagnetic dipole strength below the neutron-separation energy has been studied for the xenon isotopes with mass numbers A=124, 128, 132, and 134 in nuclear resonance fluorescence experiments using the γELBE bremsstrahlung facility at Helmholtz-Zentrum Dresden-Rossendorf and the HIγS facility at Triangle Universities Nuclear Laboratory Durham. The systematic study gained new information about the influence of the neutron excess as well as of nuclear deformation on the strength in the region of the pygmy dipole resonance. The results are compared with those obtained for the chain of molybdenum isotopes and with predictions of a random-phase approximation in a deformed basis. It turned out that the effect of nuclear deformation plays a minor role compared with the one caused by neutron excess. A global parametrization of the strength in terms of neutron and proton numbers allowed us to derive a formula capable of predicting the summed E1 strengths in the pygmy region for a wide mass range of nuclides.

[Detection of genetic determinants that define the difference of near-isogenic Triticum aestivum L. Lines in photoperiodic sensitivity].

Identification of genetic determinants that define different degrees of line sensitivity to the photoperiod was conducted on material of near-isogenic lines of the soft hexaploid wheat Triticum aestivum L. using SSR markers and markers specific to the Vrn and Ppd genes. It was established that the Ppd-s line contains a dominant Ppd-Dla allele located on chromosome 2D. This allele is characterized by a vast deletion in the gene promoter region. For two other lines (Ppd-m and Ppd-w), introgression of the Ppd-B1 gene on chromosome 2B was shown from the parental Sonora variety, which is slightly sensitive to the length of the day; however, the previously described Ppd-Bla. 1 allele was not found. Another polymorphism that can cause weak photoperiodic sensitivity, an increased amount of the Ppd-B1 gene copies, was detected for these lines.