Questionnaire-based study to assess the association between management practices and mastitis within tie-stall and free-stall dairy housing systems in Switzerland.

BACKGROUND Prophylactic measures are key components of dairy herd mastitis control programs, but some are only relevant in specific housing systems. To assess the association between management practices and mastitis incidence, data collected in 2011 by a survey among 979 randomly selected Swiss dairy farms, and information from the regular test day recordings from 680 of these farms was analyzed. RESULTS The median incidence of farmer-reported clinical mastitis (ICM) was 11.6 (mean 14.7) cases per 100 cows per year. The median annual proportion of milk samples with a composite somatic cell count (PSCC) above 200,000 cells/ml was 16.1 (mean 17.3) %. A multivariable negative binomial regression model was fitted for each of the mastitis indicators for farms with tie-stall and free-stall housing systems separately to study the effect of other (than housing system) management practices on the ICM and PSCC events (above 200,000 cells/ml). The results differed substantially by housing system and outcome. In tie-stall systems, clinical mastitis incidence was mainly affected by region (mountainous production zone; incidence rate ratio (IRR) = 0.73), the dairy herd replacement system (1.27) and farmers age (0.81). The proportion of high SCC was mainly associated with dry cow udder controls (IRR = 0.67), clean bedding material at calving (IRR = 1.72), using total merit values to select bulls (IRR = 1.57) and body condition scoring (IRR = 0.74). In free-stall systems, the IRR for clinical mastitis was mainly associated with stall climate/temperature (IRR = 1.65), comfort mats as resting surface (IRR = 0.75) and when no feed analysis was carried out (IRR = 1.18). The proportion of high SSC was only associated with hand and arm cleaning after calving (IRR = 0.81) and beef producing value to select bulls (IRR = 0.66). CONCLUSIONS There were substantial differences in identified risk factors in the four models. Some of the factors were in agreement with the reported literature while others were not. This highlights the multifactorial nature of the disease and the differences in the risks for both mastitis manifestations. Attempting to understand these multifactorial associations for mastitis within larger management groups continues to play an important role in mastitis control programs.

A Stratified Model for Psychosis Prediction in Clinical Practice

Objective: Impaired cognition is an important dimension in psychosis and its at-risk states. Research on the value of impaired cognition for psychosis prediction in at-risk samples, however, mainly relies on study-specific sample means of neurocognitive tests, which unlike widely available general test norms are difficult to translate into clinical practice. The aim of this study was to explore the combined predictive value of at-risk criteria and neurocognitive deficits according to test norms with a risk stratification approach. Method: Potential predictors of psychosis (neurocognitive deficits and at-risk criteria) over 24 months were investigated in 97 at-risk patients. Results: The final prediction model included (1) at-risk criteria (attenuated psychotic symptoms plus subjective cognitive disturbances) and (2) a processing speed deficit (digit symbol test). The model was stratified into 4 risk classes with hazard rates between 0.0 (both predictors absent) and 1.29 (both predictors present). Conclusions: The combination of a processing speed deficit and at-risk criteria provides an optimized stratified risk assessment. Based on neurocognitive test norms, the validity of our proposed 3 risk classes could easily be examined in independent at-risk samples and, pending positive validation results, our approach could easily be applied in clinical practice in the future.

Reinforcement learning in dendritic structures

The discovery of binary dendritic events such as local NMDA spikes in dendritic subbranches led to the suggestion that dendritic trees could be computationally equivalent to a 2-layer network of point neurons, with a single output unit represented by the soma, and input units represented by the dendritic branches. Although this interpretation endows a neuron with a high computational power, it is functionally not clear why nature would have preferred the dendritic solution with a single but complex neuron, as opposed to the network solution with many but simple units. We show that the dendritic solution has a distinguished advantage over the network solution when considering different learning tasks. Its key property is that the dendritic branches receive an immediate feedback from the somatic output spike, while in the corresponding network architecture the feedback would require additional backpropagating connections to the input units. Assuming a reinforcement learning scenario we formally derive a learning rule for the synaptic contacts on the individual dendritic trees which depends on the presynaptic activity, the local NMDA spikes, the somatic action potential, and a delayed reinforcement signal. We test the model for two scenarios: the learning of binary classifications and of precise spike timings. We show that the immediate feedback represented by the backpropagating action potential supplies the individual dendritic branches with enough information to efficiently adapt their synapses and to speed up the learning process.

Reinforcement learning in dendritic structures

The discovery of binary dendritic events such as local NMDA spikes in dendritic subbranches led to the suggestion that dendritic trees could be computationally equivalent to a 2-layer network of point neurons, with a single output unit represented by the soma, and input units represented by the dendritic branches. Although this interpretation endows a neuron with a high computational power, it is functionally not clear why nature would have preferred the dendritic solution with a single but complex neuron, as opposed to the network solution with many but simple units. We show that the dendritic solution has a distinguished advantage over the network solution when considering different learning tasks. Its key property is that the dendritic branches receive an immediate feedback from the somatic output spike, while in the corresponding network architecture the feedback would require additional backpropagating connections to the input units. Assuming a reinforcement learning scenario we formally derive a learning rule for the synaptic contacts on the individual dendritic trees which depends on the presynaptic activity, the local NMDA spikes, the somatic action potential, and a delayed reinforcement signal. We test the model for two scenarios: the learning of binary classifications and of precise spike timings. We show that the immediate feedback represented by the backpropagating action potential supplies the individual dendritic branches with enough information to efficiently adapt their synapses and to speed up the learning process.

Effect of eprinomectin treatment on milk yield and quality in dairy cows in South Tyrol, Italy

The effect of treatment with eprinomectin on milk yield, milk composition and somatic cell counts (SCCs) was studied in 105 dairy cows located on seven farms in South Tyrol, Italy. On each farm, half of the animals were treated with eprinomectin and the other half were used as an untreated control group. Three test day records per animal were obtained before treatment (days -117, -75 and -33) and another three test day records were obtained after treatment (days 22, 62 and 131). Test day records comprised milk yield, milk composition, SCC and days in milk. On the day of treatment, blood samples and faecal samples were taken for parasitological analysis. Cows with positive faecal egg counts yielded less milk. A significant effect of eprinomectin on milk yield was observed after treatment and was most pronounced on the second and the third test days after treatment (+1.90 kg [P=0.002] and +2.63 kg [P<0.001], respectively). Furthermore, a significant decrease in SCC was observed on the second test day after treatment.

Genotype-specific risk factors for Staphylococcus aureus in Swiss dairy herds with an elevated yield-corrected herd somatic cell count

Bovine mastitis is a frequent problem in Swiss dairy herds. One of the main pathogens causing significant economic loss is Staphylococcus aureus. Various Staph. aureus genotypes with different biological properties have been described. Genotype B (GTB) of Staph. aureus was identified as the most contagious and one of the most prevalent strains in Switzerland. The aim of this study was to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB in Swiss dairy herds with an elevated yield-corrected herd somatic cell count (YCHSCC). One hundred dairy herds with a mean YCHSCC between 200,000 and 300,000cells/mL in 2010 were recruited and each farm was visited once during milking. A standardized protocol investigating demography, mastitis management, cow husbandry, milking system, and milking routine was completed during the visit. A bulk tank milk (BTM) sample was analyzed by real-time PCR for the presence of Staph. aureus GTB to classify the herds into 2 groups: Staph. aureus GTB-positive and Staph. aureus GTB-negative. Moreover, quarter milk samples were aseptically collected for bacteriological culture from cows with a somatic cell count ≥150,000cells/mL on the last test-day before the visit. The culture results allowed us to allocate the Staph. aureus GTB-negative farms to Staph. aureus non-GTB and Staph. aureus-free groups. Multivariable multinomial logistic regression models were built to identify risk factors associated with the herd-level presence of Staph. aureus GTB and Staph. aureus non-GTB. The prevalence of Staph. aureus GTB herds was 16% (n=16), whereas that of Staph. aureus non-GTB herds was 38% (n=38). Herds that sent lactating cows to seasonal communal pastures had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 10.2, 95% CI: 1.9-56.6), compared with herds without communal pasturing. Herds that purchased heifers had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds without purchase of heifers. Furthermore, herds that did not use udder ointment as supportive therapy for acute mastitis had significantly higher odds of being infected with Staph. aureus GTB (odds ratio: 8.5, 95% CI: 1.6-58.4) or Staph. aureus non-GTB (odds ratio: 6.1, 95% CI: 1.3-27.8) than herds that used udder ointment occasionally or regularly. Herds in which the milker performed unrelated activities during milking had significantly higher odds of being infected with Staph. aureus GTB (rather than Staph. aureus non-GTB) compared with herds in which the milker did not perform unrelated activities at milking. Awareness of 4 potential risk factors identified in this study guides implementation of intervention strategies to improve udder health in both Staph. aureus GTB and Staph. aureus non-GTB herds.

Mastitis in dairy heifers: Prevalence and risk factors

Poor udder health represents a serious problem in dairy production and has been investigated intensively, but heifers generally have not been the main focus of mastitis control. The aim of this study was to evaluate the prevalence, risk factors and consequences of heifer mastitis in Switzerland. The study included 166,518 heifers of different breeds (Swiss Red Pied, Swiss Brown Cattle and Holstein). Monthly somatic cell counts (SCCs) provided by the main dairy breeding organisations in Switzerland were monitored for 3 years; the prevalence of subclinical mastitis (SCM) was determined on the basis of SCCs ≥100,000 cells/mL at the first test date. The probability of having SCM at the first test date during lactation was modelled using logistic regression. Analysed factors included data for the genetic background, morphological traits, geographical region, season of parturition and milk composition. The overall prevalence of SCM in heifers during the period from 2006 to 2010 was 20.6%. Higher frequencies of SCM were present in heifers of the Holstein breed (odds ratio, OR, 1.62), heifers with high fat:protein ratios (OR 1.97) and heifers with low milk urea concentrations combined with high milk protein concentrations (OR 3.97). Traits associated with a low risk of SCM were high set udders, high overall breeding values and low milk breeding values. Heifers with SCM on the first test day had a higher risk of either developing chronic mastitis or leaving the herd prematurely.

Focal Epilepsy: MR Imaging of Nonhemodynamic Field Effects by Using a Phase-cycled Stimulus-induced Rotary Saturation Approach with Spin-Lock Preparation.

Purpose To investigate whether nonhemodynamic resonant saturation effects can be detected in patients with focal epilepsy by using a phase-cycled stimulus-induced rotary saturation (PC-SIRS) approach with spin-lock (SL) preparation and whether they colocalize with the seizure onset zone and surface interictal epileptiform discharges (IED). Materials and Methods The study was approved by the local ethics committee, and all subjects gave written informed consent. Eight patients with focal epilepsy undergoing presurgical surface and intracranial electroencephalography (EEG) underwent magnetic resonance (MR) imaging at 3 T with a whole-brain PC-SIRS imaging sequence with alternating SL-on and SL-off and two-dimensional echo-planar readout. The power of the SL radiofrequency pulse was set to 120 Hz to sensitize the sequence to high gamma oscillations present in epileptogenic tissue. Phase cycling was applied to capture distributed current orientations. Voxel-wise subtraction of SL-off from SL-on images enabled the separation of T2* effects from rotary saturation effects. The topography of PC-SIRS effects was compared with the seizure onset zone at intracranial EEG and with surface IED-related potentials. Bayesian statistics were used to test whether prior PC-SIRS information could improve IED source reconstruction. Results Nonhemodynamic resonant saturation effects ipsilateral to the seizure onset zone were detected in six of eight patients (concordance rate, 0.75; 95% confidence interval: 0.40, 0.94) by means of the PC-SIRS technique. They were concordant with IED surface negativity in seven of eight patients (0.88; 95% confidence interval: 0.51, 1.00). Including PC-SIRS as prior information improved the evidence of the standard EEG source models compared with the use of uninformed reconstructions (exceedance probability, 0.77 vs 0.12; Wilcoxon test of model evidence, P < .05). Nonhemodynamic resonant saturation effects resolved in patients with favorable postsurgical outcomes, but persisted in patients with postsurgical seizure recurrence. Conclusion Nonhemodynamic resonant saturation effects are detectable during interictal periods with the PC-SIRS approach in patients with epilepsy. The method may be useful for MR imaging-based detection of neuronal currents in a clinical environment. (©) RSNA, 2016 Online supplemental material is available for this article.

Experimental model to evaluate in vivo and in vitro cartilage MR imaging by means of histological analyses

OBJECTIVES: Implementation of an experimental model to compare cartilage MR imaging by means of histological analyses. MATERIAL AND METHODS: MRI was obtained from 4 patients expecting total knee replacement at 1.5 and/or 3T prior surgery. The timeframe between pre-op MRI and knee replacement was within two days. Resected cartilage-bone samples were tagged with Ethi((R))-pins to reproduce the histological cutting course. Pre-operative scanning at 1.5T included following parameters for fast low angle shot (FLASH: TR/TE/FA=33ms/6ms/30 degrees , BW=110kHz, 120mmx120mm FOV, 256x256 matrix, 0.65mm slice-thickness) and double echo steady state (DESS: TR/TE/FA=23.7ms/6.9ms/40 degrees , BW=130kHz, 120x120mm FOV, 256x256 matrix, 0.65mm slice-thickness). At 3T, scan parameters were: FLASH (TR/TE/FA=12.2ms/5.1ms/10 degrees , BW=130kHz, 170x170mm FOV, 320x320, 0.5mm slice-thickness) and DESS (TR/TE/FA=15.6ms/4.5ms/25 degrees , BW=200kHz, 135mmx150mm FOV, 288x320matrix, 0.5mm slice-thickness). Imaging of the specimens was done the same day at 1.5T. MRI (Noyes) and histological (Mankin) score scales were correlated using the paired t-test. Sensitivity and specificity for the detection of different grades of cartilage degeneration were assessed. Inter-reader and intra-reader reliability was determined using Kappa analysis. RESULTS: Low correlation (sensitivity, specificity) was found for both sequences in normal to mild Mankin grades. Only moderate to severe changes were diagnosed with higher significance and specificity. The use of higher field-strengths was advantageous for both protocols with sensitivity values ranging from 13.6% to 93.3% (FLASH) and 20.5% to 96.2% (DESS). Kappa values ranged from 0.488 to 0.944. CONCLUSIONS: Correlating MR images with continuous histological slices was feasible by using three-dimensional imaging, multi-planar-reformat and marker pins. The capability of diagnosing early cartilage changes with high accuracy could not be proven for both FLASH and DESS.

Granulocyte colony stimulating factor supports liver regeneration in a surgical small for size liver remnant mouse model

ntense liver regeneration and almost 100% survival follows partial hepatectomy of up to 70% of liver mass in rodents. More extensive resections of 70 to 80% have an increased mortality and partial hepatectomies of >80% constantly lead to acute hepatic failure and death in mice. The aim of the study was to determine the effect of systemically administered granulocyte colony stimulating factor (G-CSF) on animal survival and liver regeneration in a small for size liver remnant mouse model after 83% partial hepatectomy (liver weight <0.8% of mouse body weight). Methods: Male Balb C mice (n=80, 20-24g) were preconditioned daily for five days with 5μg G-CSF subcutaneously or sham injected (aqua ad inj). Subsequently 83% hepatic resection was performed and daily sham or G-CSF injection continued. Survival was determined in both groups (G-CSF n=35; Sham: n=33). In a second series BrdU was injected (50mg/kg Body weight) two hours prior to tissue harvest and animals euthanized 36 and 48 hours after 83% liver resection (n=3 each group). To measure hepatic regeneration the BrdU labeling index and Ki67 expression were determined by immunohistochemistry by two independent observers. Harvested liver tissue was dried to constant weight at 65 deg C for 48 hours. Results: Survival was 0% in the sham group on day 3 postoperatively and significantly better (26.2% on day 7 and thereafter) in the G-CSF group (Log rank test: p<0.0001). Dry liver weight was increased in the G-CSF group (T-test: p<0.05) 36 hours after 83% partial hepatectomy. Ki67 expression was elevated in the G-CSF group at 36 hours (2.8±2.6% (Standard deviation) vs 0.03±0.2%; Rank sum test: p<0.0001) and at 48 hours (45.1±34.6% vs 0.7±1.0%; Rank sum test: p<0.0001) after 83% liver resection. BrdU labeling at 48 hours was 0.1±0.3% in the sham and 35.2±34.2% in the G-CSF group (Rank sum test: p<0.0001) Conclusions: The surgical 83% resection mouse model is suitable to test hepatic supportive regimens in the setting of small for size liver remnants. Administration of G-CSF supports hepatic regeneration after microsurgical 83% partial hepatectomy and leads to improved long-term survival in the mouse. G-CSF might prove to be a clinically valuable supportive substance in small for size liver remnants in humans after major hepatic resections due to primary or secondary liver tumors or in the setting of living related liver donation.

Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis

A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athymic rnu-rats by surgical excision of the femoral vessels. Blood flow of the limb was monitored for 60 days by laser Doppler imaging. Following a short postoperative period of substantially depressed perfusion, the animals showed a status of moderate hind limb ischemia from day 14 onwards. Thereafter, the perfusion remained at a constant level (55.5% of normal value) until the end of the observation period. Histopathological assessment of the ischemic musculature on postoperative days 28 and 60 showed essentially no inflammatory cell infiltrate or fibrosis. However, the mitochondrial activity and capillary-to-fiber ratio of the muscular tissue was reduced to 52.7% of normal, presenting with a significant weakness of the ischemic limb evidenced by a progressive decline in performance. Intramuscular injection of culture-expanded human endothelial progenitor cells (EPC) resulted in a significant increase in blood flow (82.0+/-3.5% of normal), capillary density (1.60+/-0.08/muscle fiber) and smooth muscle covered arterioles (8.0+/-0.6/high power field) in the ischemic hind limb as compared to controls (55.0+/-3.1%; 0.99+/-0.03; 5.0+/-0.2). In conclusion, chronic, moderate hind limb ischemia with consistently reduced perfusion levels persisting over a prolonged period can be established reliably in rnu athymic nude rats and is responsive to pro-angiogenic treatments such as EPC transplantation. This study provides a detailed protocol of a highly reproducible reference model to test novel therapeutic options for limb ischemia.