Evaluation of sensor-based health monitoring in dairy cows: Exploiting rumination times for health alerts around parturition.

The use of sensor-based measures of rumination time as a parameter for early disease detection has received significant attention in scientific research. This study aimed to assess the accuracy of health alerts triggered by a sensor-based accelerometer system within 2 different management strategies on a commercial dairy farm. Multiparous Holstein cows were enrolled during the dry-off period and randomly allocated to conventional (CON) or sensor-based (SEN) management groups at calving. All cows were monitored for disorders for a minimum of 10 DIM following standardized operating procedures (SOPs). The CON group (n = 199) followed an established monitoring protocol on the farm. The health alerts of this group were not available during the study but were later included in the analysis. The SEN group (n = 197) was only investigated when the sensor system triggered a health alert, and a more intensive monitoring approach according to the SOPs was implemented. To analyze the efficiency of the health alerts in detecting disorders, the sensitivity (SE) and specificity (SP) of health alerts were determined for the CON group. In addition, all cows were divided into 3 subgroups based on the status of the health alerts and their health status, to retrospectively compare the course of rumination time. Most health alerts (87%, n = 217) occurred on DIM 1. For the confirmation of diagnoses, health alerts showed SE and SP levels of 71% and 47% for CON cows. In SEN cows, a SE of 71% and 75% and SP of 48% and 43% were found for the detection of ketosis and hypocalcemia, respectively. The rumination time of the subgroups was affected by DIM and the interaction between DIM and the status of health alert and health condition.

Large-Area SiPM Pixels (LASiPs): A cost-effective solution towards compact large SPECT cameras.

Single Photon Emission Computed Tomography (SPECT) scanners based on photomultiplier tubes (PMTs) are still largely employed in the clinical environment. A standard camera for full-body SPECT employs ~50-100 PMTs of 4-8 cm diameter and is shielded by a thick layer of lead, becoming a heavy and bulky system that can weight a few hundred kilograms. The volume, weight and cost of a camera can be significantly reduced if the PMTs are replaced by silicon photomultipliers (SiPMs). The main obstacle to use SiPMs in full-body SPECT is the limited size of their sensitive area. A few thousand channels would be needed to fill a camera if using the largest commercially-available SiPMs of 6 × 6 mm2. As a solution, we propose to use Large-Area SiPM Pixels (LASiPs), built by summing individual currents of several SiPMs into a single output. We developed a LASiP prototype that has a sensitive area 8 times larger than a 6 × 6 mm2 SiPM. We built a proof-of-concept micro-camera consisting of a 40 × 40 × 8 mm3 NaI(Tl) crystal coupled to 4 LASiPs. We evaluated its performance in a central region of 15×15 mm2, where we were able to reconstruct images of a 99mTc capillary with an intrinsic spatial resolution of ~2 mm and an energy resolution of ~11.6% at 140 keV. We used these measurements to validate Geant4 simulations of the system. This can be extended to simulate a larger camera with more and larger pixels, which could be used to optimize the implementation of LASiPs in large SPECT cameras. We provide some guidelines towards this implementation.

Intestinal insulin/IGF1 signalling through FoxO1 regulates epithelial integrity and susceptibility to colon cancer.

Obesity promotes the development of insulin resistance and increases the incidence of colitis-associated cancer (CAC), but whether a blunted insulin action specifically in intestinal epithelial cells (IECs) affects CAC is unknown. Here, we show that obesity impairs insulin sensitivity in IECs and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibit enhanced CAC development as a consequence of impaired restoration of gut barrier function. Blunted insulin signalling retains the transcription factor FOXO1 in the nucleus to inhibit expression of Dsc3, thereby impairing desmosome formation and epithelial integrity. Both IEC-specific nuclear FoxO1ADA expression and IEC-specific Dsc3 inactivation recapitulate the impaired intestinal integrity and increased CAC burden. Spontaneous colonic tumour formation and compromised intestinal integrity are also observed upon IEC-specific coexpression of FoxO1ADA and a stable Myc variant, thus suggesting a molecular mechanism through which impaired insulin action and nuclear FOXO1 in IECs promotes CAC.

Short communication: Pilot study on hormonal, metabolic, and behavioral stress response to treatment of claw horn lesions in acutely lame dairy cows.

Short-term effects of therapeutic claw trimming in acutely lame cows (n=21) with nonadvanced claw horn lesions on the endocrine, metabolic, and behavioral stress responses were investigated in comparison to regular claw trimming in nonlame control cows (n=21). Controls were matched to lame cows by parity and stage of lactation. Lame cows suffering from typical sole ulcers or white line disease were blinded and randomly assigned to 2 treatments, receiving 15 min before interventions either ketoprofen (n=11; 3mg/kg of BW intramuscularly; Romefen, Merial, Lyon, France) or placebo (n=10; saline in equivalent amount and route of administration). All cows underwent functional claw trimming in lateral recumbency on a surgical tipping table, and claw horn lesions in lame cows were conventionally treated (removal of loose horn, block on opposing claw, bandaging of affected claw). Blood samples collected 15 min before, at the end, and 24h after claw trimming were analyzed for concentrations of cortisol, fatty acids, lactate, and glucose, and fecal samples (collected before treatment and after 24 h) for cortisol metabolites. Behavioral stress responses during functional and therapeutic claw trimming were recorded. Concentrations of blood cortisol, fatty acids, glucose, and fecal cortisol metabolites were higher in lame than in nonlame cows after treatment. During claw treatment, more leg movements were recorded for lame cows than nonlame cows. Pre-emptive administration of ketoprofen had no obvious effects on stress responses to therapeutic claw trimming. Treatments of claw horn lesions caused a significant stress and pain reaction in acutely lame cows, demonstrating the necessity of adequate pain management protocols for such interventions.

Prostaglandin E2 as a read out for endotoxin detection in a bovine whole blood assay.

The detection of endotoxin contamination is an essential part of drug safety testing. The rabbit pyrogen test (RPT), the limulus amoebocyte lysate (LAL) test, and the monocyte activation test (MAT) are established methods for the detection of pyrogens. However, the RPT is insufficiently standardized; the LAL test is solely capable of identifying the presence of endotoxins, whereas the use of the MAT is limited by the availability of human blood. Here, we introduce a new procedure for testing endotoxin contamination using prostaglandin E2 (PGE2 ) release from bovine whole blood. We incubated bovine whole blood overnight with lipopolysaccharide (LPS) from Escherichia coli 0111:B4, concentrations ranging from 1.56 to 12.5 pg/mL, and found significantly increased PGE2 production for even the lowest LPS concentrations. Testing the possibility of storing the blood at 4 °C before use also yielded positive results as 1.56 pg/mL still significantly increased PGE2 production, thus suggesting some flexibility of the assay regarding time. These results emphasize the potential of using bovine whole blood for highly sensitive endotoxin testing. As a perspective, currently ongoing research aims to show whether the assay is also capable of detecting nonendotoxin pyrogens.

A trapped-ion-based quantum byte with 10(-5) next-neighbour cross-talk.

The addressing of a particular qubit within a quantum register is a key pre-requisite for scalable quantum computing. In general, executing a quantum gate with a single qubit, or a subset of qubits, affects the quantum states of all other qubits. This reduced fidelity of the whole-quantum register could prevent the application of quantum error correction protocols and thus preclude scalability. Here we demonstrate addressing of individual qubits within a quantum byte (eight qubits) and measure the error induced in all non-addressed qubits (cross-talk) associated with the application of single-qubit gates. The quantum byte is implemented using microwave-driven hyperfine qubits of (171)Yb(+) ions confined in a Paul trap augmented with a magnetic gradient field. The measured cross-talk is on the order of 10(-5) and therefore below the threshold commonly agreed sufficient to efficiently realize fault-tolerant quantum computing. Hence, our results demonstrate how this threshold can be overcome with respect to cross-talk.

Intra-aortic balloon pump (IABP) counterpulsation improves cerebral perfusion in patients with decreased left ventricular function.

BACKGROUND: The current goal of treatment after acute ischemic stroke is the increase of cerebral blood flow (CBF) in ischemic brain tissue. Intra-aortic balloon pump (IABP) counterpulsation in the setting of cardiogenic shock is able to reduce left ventricular afterload and increase coronary blood flow. The effects of an IABP on CBF have not been sufficiently examined. We hypothesize that the use of an IABP especially enhances cerebral blood flow in patients with pre-existing heart failure. METHODS: In this pilot study, 36 subjects were examined to investigate the effect of an IABP on middle cerebral artery (MCA) transcranial Doppler (TCD) flow velocity change and relative CBF augmentation by determining velocity time integral changes (ΔVTI) in a constant caliber of the MCA compared to a baseline measurement without an IABP. Subjects were divided into two groups according to their left ventricular ejection fraction (LVEF): Group 1 LVEF >30% and Group 2 LVEF ≤30%. RESULTS: Both groups showed an increase in CBF using an IABP. Patients with a LVEF ≤30% showed a significantly higher increase of ΔVTI in the MCA under IABP augmentation compared to patients with a LVEF >30% (20.9% ± 3.9% Group 2 vs.10.5% ± 2.2% Group 1, p<0,05). The mean arterial pressure (MAP) increased only marginally in both groups under IABP augmentation. CONCLUSIONS: IABP improves cerebral blood flow, particularly in patients with pre-existing heart failure and highly impaired LVEF. Hence, an IABP might be a treatment option to improve cerebral perfusion in selected patients with cerebral misperfusion and simultaneously existing severe heart failure.

High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest.

INTRODUCTION: After cardiac arrest due to acute coronary syndromes (ACS) therapeutic hypothermia (HT) is the standard care to reduce neurologic damage. Additionally, the concomitant medical treatment with aspirin and a P2Y12 receptor inhibitor like clopidogrel (Cl), prasugrel (Pr) or ticagrelor (Ti) is mandatory. The platelet inhibitory effect of these drugs under hypothermia remains unclear. METHODS: 164 patients with ACS were prospectively enrolled in this study. 84 patients were treated with HT, 80 patients were under normothermia (NT). All patients were treated with aspirin and one of the P2Y12 receptor inhibitors Cl, Pr or Ti. 24h after the initial loading dose the platelet reactivity index (PRI/VASP-index) was determined to achieve the platelet inhibitory effect. RESULTS: In the HT-group the PRI/VASP-index was significantly higher compared to the NT-group (54.86%±25.1 vs. 28.98%±22.8; p<0.001). In patients under HT receiving Cl, the platelet inhibition was most markedly reduced (HT vs. NT: 66.39%±19.1 vs. 33.36%±22.1; p<0.001) compared to Pr (HT vs. NT: 37.6%±25.0 vs. 27.04%±25.5; p=0.143) and Ti (HT vs. NT: 41.5%±21.0 vs. 17.83%±14.5; p=0.009). The rate of non-responder defined as PRI/VASP-index>50% was increased in HT compared to NT (60.7% vs. 22.5%; p<0.001) with the highest rates in the group receiving Cl (CL: 82% vs. 26%, p<0.001; Pr: 32% vs. 23%; n.s.; Ti: 30% vs. 8%, n.s.). CONCLUSION: The platelet inhibitory effect in patients treated with HT after cardiac arrest is significantly reduced. This effect was most marked with the use of Cl. The new P2Y12-inhibitors Pr and Ti improved platelet inhibition in HT, but could not completely prevent non-responsiveness.

As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout.

We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid-femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤ 360 µmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.

Implantable cardioverter defibrillator lead implantation in patients with a persistent left superior vena cava--feasibility, chances, and limitations: representative cases in adults.

AIMS: Device implantation may be challenging in patients with venous abnormalities. The most common congenital variation--frequently associated with other congenital abnormalities--is described as persistent left superior vena cava (PLSVC). METHODS AND RESULTS: The present case series demonstrates successful implantable cardioverter defibrillator (ICD) lead implantation in the most common anatomic variations of PLSVC. All types of current ICD models (single and dual chamber, VDD, and cardiac resynchronization therapy devices) were used. Angiographic findings and implantation techniques (e.g. guiding and diagnostic catheters, wires, occlusion balloons, and rotation sequences) are presented in images and movie sequences. CONCLUSION: Device implantation in patients with PLSVC may be complex but a successful transvenous approach is possible in most of the cases. Careful imaging prior to implantation procedure is essential for understanding the individual anatomy and in order to choose adequate material and implantation strategy.

A scalable, fast, and multichannel arbitrary waveform generator.

This article reports on the development of a multichannel arbitrary waveform generator that simultaneously generates arbitrary voltage waveforms on 24 independent channels with a dynamic update rate of up to 25 Msps. A real-time execution of a single waveform and/or sequence of multiple waveforms in succession, with a user programmable arbitrary sequence order is provided under the control of a stand-alone sequencer circuit implemented using a field programmable gate array. The device is operated using an internal clock and can be synced to other devices by means of transistor-transistor logic (TTL) pulses. The device can provide up to 24 independent voltages in the range of up to ± 9 V with a dynamic update-rate of up to 25 Msps and a power consumption of less than 35 W. Every channel can be programmed for 16 independent arbitrary waveforms that can be accessed during run time with a minimum switching delay of 160 ns. The device has a low-noise of 250 µV(rms) and provides a stable long-term operation with a drift rate below 10 µV/min and a maximum deviation less than ± 300 µV(pp) over a period of 2 h.

Pre-hospital discharge testing after implantable cardioverter defibrillator implantation: a measure of safety or out of date? A retrospective analysis of 975 patients.

AIMS: The present study evaluates the relevance and additional safety value of pre-hospital discharge (PHD) testing in patients with implantable cardioverter defibrillator (ICD) therapy. METHODS: From June 1998 to May 2009, 975 patients (830 male, 145 female) with ICD were screened retrospectively for failed PHD and analysed for its consequences, risk factors, and patient characteristics after successful intra-operative testing in the implantation procedure. RESULTS: Pre-hospital discharge testing procedure was performed in 809 cases. No serious adverse events (e.g. death, persistant ventricular fibrillation or ventricular tachycardia, stroke) occurred. The overall incidence of failed PHD was 1.4% (n = 11). The underlying mechanisms were defibrillation threshold failure in 9/11 cases and sensing failure in 2/11 cases. CONCLUSIONS: In this study predictors for PHD-failure are: (i) cardiomyopathy other than ischaemic or dilative, (ii) young age, and (iii) small or very large left ventricular end-diastolic diameter ( < 40 or > 65 mm). Particularly, (i) manufacture of device or leads, (ii) lead design, (iii) medical treatment, or (iv) gender have no significant influence on PHD failure.

[Maintenance of AAI(R) mode at the time of generator replacement]. / Fortbestehen des AAI(R)-Modus zum Austauschzeitpunkt.

BACKGROUND: In isolated sinus node disease single lead atrial stimulation is recommended. However, an inherent risk includes emerging AV node disturbances with serious bradycardia in the follow-up. This possible scenario frequently results in the implantation of an additional ventricular lead. PATIENTS AND METHODS: In this single-centre retrospective study the interval between 1982 and 2007 was analysed. During this period a total of 6,309 antibradycardia pacemakers were implanted for the first time. Ten percent (n=631) of these devices were single lead atrial pacemakers for treatment of the sick sinus syndrome (SSS). In these 26 years 136 pacemaker replacement operations were performed. During this procedure a thorough reevaluation of the stimulation mode was done. RESULTS: In 80.6% (n=112) AAI(R) was continued, in 10.1% (n=14) the system was upgraded to DDD(R), and in 9.3% the mode was changed to VVI(R). There were no significant differences in the lifetime of the AAI(R) pacemakers up to the time of this operation: 7.9 vs 6.3 vs 7.0 years. CONCLUSION: The single lead atrial pacing mode in SSS is mostly safe also in the long term. A premature change of stimulation mode is rarely necessary.

[Hyperuricemia and gout: diagnosis and therapy]. / Hyperurikämie und Gicht : Diagnostik und Therapie.

In our modern society hyperuricemia is one of the most frequent metabolism disturbances. So far, every fourth man and every tenth woman suffer from an asymptomatic or a symptomatic hyperuricemia named gout. Mostly, over nutrition and malnutrition as well as other secondary factors with a genetically determined renal secretion disturbance of uric acid lead to an increase of serum uric acid. By deposition of uric acid crystals in tissues with intermittent immunologic activation of inflammation cells a manifestation of gout can be seen. The clinical image of gout varies widely. It may manifest as acute or chronic arthritis, tophi on the skin, subcutaneous tissue and the skeletal system as well as urate nephropathy. To eliminate the consequences of hyperuricemia in the long term, apart from a thorough anamnesis of nutritional habits a general examination of metabolic parameters is necessary to exclude a metabolic syndrome and other causes for a secondarily caused hyperuricemia. As gout is very often primarily caused by a renal secretion disturbance of uric acid special diagnostics should be done. Basing on literature research and inclusion of experts opinions this article represents the therapeutically options in treatment of hyperuricemia and gout with their resulting side effects and contraindications.

Distinct factors correlating with adverse cardiac events after major vascular surgery.

INTRODUCTION: Cardiovascular complications remain the principal cause of both morbidity and mortality after major vascular surgery. The well-known coincidence between vascular disease and coronary artery disease provided the rationale for a detailed analysis of major perioperative cardiovascular complications in their relation to preoperative and intraoperative parameter METHODS AND PATIENTS: 90 patients scheduled to undergo either femoral-popliteal bypass (n = 74) or repair of an infrarenal aortic aneurysm (n = 16) were prospectively included in the study. All patients had no signs of unstable cardiac disease and required no cardiac testing. Both preoperative and intraoperative parameter were correlated to adverse cardiac events (cardiac death and myocardial infarction -MI). RESULTS: Univariate analysis identified the following parameter to be significantly related to cardiac complications: prior MI and intraoperative hypertension (systolic blood pressure above 200 mmHg). In contrast perioperative betablocker therapy was revealed to be protective. In multivariate analysis the history of MI and intraoperative hypertension correlated with poor cardiac outcome. CONCLUSIONS: Our results underline the importance of the individual history in predicting perioperative risk and corroborate the beneficial effects of long-standing beta-blocker therapy. Additionally the significance of stable intraoperative hemodynamic parameter is demonstrated.