A comparison of the performance of contemporary, historical, and cross-lab controls in QTc assessment in conscious nonhuman primates.

Cardiovascular safety pharmacology and toxicology studies include vehicle control animals in most studies. Electrocardiogram data on common vehicles is accumulated relatively quickly. In the interests of the 3Rs principles it may be useful to use this historical information to reduce the use of animals or to refine the sensitivity of studies. We used implanted telemetry data from a large nonhuman primate (NHP) cardiovascular study (n = 48) evaluating the effect of moxifloxacin. We extracted 24 animals to conduct a n = 3/sex/group analysis. The remaining 24 animals were used to generate 1000 unique combinations of 3 male and 3 female NHP to act as control groups for the three treated groups in the n = 3/sex/group analysis. The distribution of treatment effects, median minimum detectable difference (MDD) values were gathered from the 1000 studies. These represent contemporary controls. Data were available from 42 NHP from 3 other studies in the same laboratory using the same technology. These were used to generate 1000 unique combinations of 6, 12, 18, 24 and 36 NHP to act as historical control animals for the 18 animals in the treated groups of the moxifloxacin study. Data from an additional laboratory were also available for 20 NHP. The QT, RR and QT-RR data from the three sources were comparable. However, differences in the time course of QTc effect in the vehicle data from the two laboratories meant that it was not possible to use cross-lab controls. In the case of historical controls from the same laboratory, these could be used in place of the contemporary controls in determining a treatment's effect. There appeared to be an advantage in using larger (≥18) group sizes for historical controls. These data support the opportunity of using historical controls to reduce the number of animals used in new cardiovascular studies.

Improving Telemetry use in the Acute Assessment Unit.

BACKGROUND AND AIMS: Despite published guidelines, telemetry use is inappropriate in 25-43% of cases. This impacts patient safety and telemetry effectiveness. QI methodology was used to review telemetry in a hospital acute medical unit with the aim of reducing inappropriate use and addressing alarm fatigue. METHODS: A 'Telemetry Indication Form' was created. Eight weeks of baseline data was collated before introducing the 'Indication Form'. Four plan-do-study-act cycles were conducted. At each cycle, data was analysed using statistical process control charts. RESULTS: Inappropriate telemetry use significantly reduced from 32% to 4%. Total telemetry use also fell. Unfortunately, interventions to address alarm rates did not result in significant reduction in false alarms. CONCLUSIONS: A 'Telemetry Indication Form' has significant potential to improve patient safety through reducing inappropriate use.

Comparing the outcomes and costs of cardiac monitoring with implantable loop recorders and mobile cardiac outpatient telemetry following stroke using real-world evidence.

Aim: Patients with ischemic stroke (IS) commonly undergo monitoring to identify atrial fibrillation with mobile cardiac outpatient telemetry (MCOT) or implantable loop recorders (ILRs). The authors compared readmission, healthcare cost and survival in patients monitored post-stroke with either MCOT or ILR. Materials & methods: The authors used claims data from Optum's de-identified Clinformatics® Data Mart Database to identify patients with IS hospitalized from January 2017 to December 2020 who were prescribed ambulatory cardiac monitoring via MCOT or ILR. They compared the costs associated with the initial inpatient visit as well as the rate and causes of readmission, survival and healthcare costs over the following 18 months. Datasets were balanced using patient baseline and hospitalization characteristics. Multivariable generalized linear gamma regression was used for cost comparisons. Cox proportional hazard regression was used for survival and readmission analysis. Sub-cohorts were analyzed based on the severity of the index IS. Results: In 2244 patients, readmissions were significantly lower in the MCOT monitored group (30.2%) compared with the ILR group (35.4%) (hazard ratio [HR] 1.23; 95% CI: 1.04-1.46). Average cost over 18 months starting with the index IS was $27,429 (USD) lower in the MCOT group (95% CI: $22,353-$32,633). Survival difference bordered on statistical significance and trended to lower mortality in MCOT (8.9%) versus ILR (11.3%) (HR 1.30; 95% CI: 1:00-1.69), led by significance in patients with complications or comorbidities with the index event (MCOT 7.5%, ILR 11.5%; HR 1.62; 95% CI: 1.11-2.36). Conclusion: The use of MCOT versus ILR as the primary monitor following IS was associated with significant decreases in readmission, lower costs for the initial IS and total care over the next 18 months, significantly lower mortality for patients with complications and comorbidities at the index stroke, and a trend toward improved survival across all patients.

A systematic review of the use of in-vehicle telematics in monitoring driving behaviours.

BACKGROUND: Road traffic deaths are increasing globally, and preventable driving behaviours are a significant cause of these deaths. In-vehicle telematics has been seen as technology that can improve driving behaviour. The technology has been adopted by many insurance companies to track the behaviours of their consumers. This systematic review presents a summary of the ways that in-vehicle telematics has been modelled and analysed. METHODOLOGY: Electronic searches were conducted on Scopus and Web of Science. Studies were only included if they had a sample size of 10 or more participants, collected their data over at least multiple days, and were published during or after 2010. 45 relevant papers were included in the review. 27 of these articles received a rating of "good" in the quality assessment. RESULTS: We found a divide in the literature regarding the use of in-vehicle telematics. Some articles were interested in the utility of in-vehicle telematics for insurance purposes, while others were interested in determining the influence that in-vehicle telematics has on driving behaviour. Machine learning analyses were the most common forms of analysis seen throughout the review, being especially common in articles with insurance-based outcomes. Acceleration, braking, and speed were the most common variables identified in the review. CONCLUSION: We recommend that future studies provide the demographical information of their sample so that the influence of in-vehicle telematics on the driving behaviours of different groups can be understood. It is also recommended that future studies use multi-level models to account for the hierarchical structure of the telematics data. This hierarchical structure refers to the individual trips for each driver.

Timing is everything; operational changes at a pumping station with a gravity sluice to provide safe downstream passage for silver European eels and deliver considerable financial savings.

Catadromous European eel (Anguilla anguilla) are a critically endangered fish species due in part to in-river anthropogenic barriers (e.g., pumping stations, weirs, hydropower facilities). European legislation stipulates that safe downstream passage must be provided at hazardous intakes. Where present, gravity sluices have the potential to act as safe and low-cost downstream passage for seaward migrating silver eels at pumping station, but operational changes are required. This study used catchment-wide and fine-scale acoustic telemetry to investigate if operational changes (OC) at a pumping station (PS) with a co-located gravity sluice (GS) facilitated safe downstream passage for silver European eels. Specifically, night-time pump operations were ceased, river levels prior to sluicing were elevated and the GS was opened during key eel migration windows, i.e., at night during the new moon phase in autumn. No tagged eels passed through any pumps and the majority (2018 = 87.5%, 2020 = 88.9%) that approached the PS during OC passed downstream through the GS. Most eels approached during the first period of night sluicing after release (2018 = 73.9% and 2020 = 76.5%) and passed downstream during the first sluice event they experienced at the PS (2018 = 66.7% and 2020 = 75.0%). During the final approach prior to passage, very few retreats back upstream occurred at a median (IQR) distance of 34 (7.25) m from the GS and were predominantly a short distance (1-8 m). Overall, OC at a PS with a GS are considered a win-win-win, despite opening the sluice for <3% of the study period, given safe downstream passage was maximised, the financial benefits of sluicing water (∼£14,670 in direct operational costs over two years) and the relative ease of implementation.

Low-Cost GNSS and PPP-RTK: Investigating the Capabilities of the u-blox ZED-F9P Module.

GNSS has become ubiquitous in high-precision applications, although the cost of high-end GNSS receivers remains a major obstacle for many applications. Recent advances in GNSS receiver technology have led to the development of low-cost GNSS receivers, making high-precision positioning available to a wider range of users. One such technique for achieving high-precision positioning is Precise Point Positioning-Real Time Kinematic (PPP-RTK). It is a GNSS processing technique that combines the PPP and RTK approaches to provide high-precision positioning in real time without the need for a base station. In this work, we aim to assess the performance of the low-cost u-blox ZED-F9P GNSS module in PPP-RTK mode using the low-cost u-blox ANN-MB antenna. The experiment was designed to investigate both the time it takes the receiver to resolve the phase ambiguity and to determine the positioning accuracies achievable. Results showed that the u-blox ZED-F9P GNSS module could achieve centimeter-level positioning accuracy in about 60 s in PPP-RTK mode. These results make the PPP-RTK technique a good candidate to fulfill the demand for mass-market accurate and robust navigation since uses satellite-based corrections to provide accurate positioning information without the need for a local base station or network. Furthermore, due to its rapid acquisition capabilities and accurate data georeferencing, the technique has the potential to serve as a valuable method to improve the accuracy of the three-S techniques (GIS, remote sensing, and GPS/GNSS).

Scheduling Sparse LEO Satellite Transmissions for Remote Water Level Monitoring.

This paper explores the use of low earth orbit (LEO) satellite links in long-term monitoring of water levels across remote areas. Emerging sparse LEO satellite constellations maintain sporadic connection to the ground station, and transmissions need to be scheduled for satellite overfly periods. For remote sensing, the energy consumption optimization is critical, and we develop a learning approach for scheduling the transmission times from the sensors. Our online learning-based approach combines Monte Carlo and modified k-armed bandit approaches, to produce an inexpensive scheme that is applicable to scheduling any LEO satellite transmissions. We demonstrate its ability to adapt in three common scenarios, to save the transmission energy 20-fold, and provide the means to explore the parameters. The presented study is applicable to wide range of IoT applications in areas with no existing wireless coverages.

Human locomotion over obstacles reveals real-time prediction of energy expenditure for optimized decision-making.

Despite decades of evidence revealing a multitude of ways in which animals are adapted to minimize the energy cost of locomotion, little is known about how energy expenditure shapes adaptive gait over complex terrain. Here, we show that the principle of energy optimality in human locomotion can be generalized to complex task-level locomotor behaviours requiring advance decision-making and anticipatory control. Participants completed a forced-choice locomotor task requiring them to choose between discrete multi-step obstacle negotiation strategies to cross a 'hole' in the ground. By modelling and analysing mechanical energy cost of transport for preferred and non-preferred manoeuvres over a wide range of obstacle dimensions, we showed that strategy selection was predicted by relative energy cost integrated across the complete multi-step task. Vision-based remote sensing was sufficient to select the strategy associated with the lowest prospective energy cost in advance of obstacle encounter, demonstrating the capacity for energetic optimization of locomotor behaviour in the absence of online proprioceptive or chemosensory feedback mechanisms. We highlight the integrative hierarchic optimizations that are required to facilitate energetically efficient locomotion over complex terrain and propose a new behavioural level linking mechanics, remote sensing and cognition that can be leveraged to explore locomotor control and decision-making.

Simultaneous assessment of central nervous and respiratory systems using jacketed telemetry in socially-housed rats: Application of the "3Rs" principles in core battery safety pharmacology studies.

Central nervous (CNS) and respiratory systems are routinely investigated in safety pharmacology core battery studies. For small molecules, the assessment of both vital organ systems is frequently done in rats in two distinct studies. With the advent of a miniaturized technology of jacketed external telemetry for rats (DECRO system), the simultaneous assessment of modified Irwin's or functional observational battery (FOB) test and respiratory (Resp) studies has become possible within a single study. Therefore, the objectives of this study were to perform the FOB and the Resp studies simultaneously in pair-housed rats fitted with jacketed telemetry, and to assess the feasibility and the outcome of this combination in control, baclofen, caffeine, and clonidine treated groups, i.e., with three agents having both respiratory and CNS effects. Our results provided evidence that performing both Resp and FOB assessment simultaneously in the same rat was feasible and the outcome was successful. The expected CNS and respiratory effects of the 3 reference compounds were accurately captured in each assay confirming the results' relevance. In addition, heart rate and activity level were recorded as additional parameters making this design as an enhanced approach for nonclinical safety assessment in rats. This work provides clear evidence that the "3Rs" principles can be effectively applied in core battery safety pharmacology studies while remaining in compliance with worldwide regulatory guidelines. Both reduction in animal use and refinements in procedures are demonstrated with this model.

Spatio-Temporal Development of Vegetation Carbon Sinks and Sources in the Arid Region of Northwest China.

Drylands, which account for 41% of Earth's land surface and are home to more than two billion people, play an important role in the global carbon balance. This study analyzes the spatio-temporal patterns of vegetation carbon sinks and sources in the arid region of northwest China (NWC), using the net ecosystem production (NEP) through the Carnegie-Ames-Stanford approach (CASA). It quantitatively evaluates regional ecological security over a 20-year period (2000-2020) via a remote sensing ecological index (RSEI) and other ecological indexes, such as the Normalized Difference Vegetation Index (NDVI), fraction of vegetation cover (FVC), net primary productivity (NPP), and land use. The results show that the annual average carbon capacity of vegetation in NWC changed from carbon sources to carbon sinks, and the vegetation NEP increased at a rate of 1.98 gC m-2 yr-1 from 2000 to 2020. Spatially, the annual NEP in northern Xinjiang (NXJ), southern Xinjiang (SXJ) and Hexi Corridor (HX) increased at even faster rates of 2.11, 2.22, and 1.98 gC m-2 yr-1, respectively. Obvious geographically heterogeneous distributions and changes occurred in vegetation carbon sinks and carbon sources. Some 65.78% of the vegetation areas in NWC were carbon sources during 2000-2020, which were concentrated in the plains, and SXJ, the majority carbon sink areas are located in the mountains. The vegetation NEP in the plains exhibited a positive trend (1.21 gC m-2 yr-1) during 2000-2020, but this speed has slowed since 2010. The vegetation NEP in the mountain exhibited only intermittent changes (2.55 gC m-2 yr-1) during 2000-2020; it exhibited a negative trend during 2000-2010, but this trend has reversed strongly since 2010. The entire ecological security of NWC was enhanced during the study period. Specifically, the RSEI increased from 0.34 to 0.49, the NDVI increased by 0.03 (17.65%), the FVC expanded by 19.56%, and the NPP increased by 27.44%. Recent positive trends in NDVI, FVC and NPP have enhanced the capacity of vegetation carbon sinks, and improved the eco-environment of NWC. The scientific outcomes of this study are of great importance for maintaining ecological stability and sustainable economic development along China's Silk Road Economic Belt.

Postoperative Severity Assessment in Sheep.

INTRODUCTION: Sheep are frequently used in translational surgical orthopedic studies. Naturally, a good pain management is mandatory for animal welfare, although it is also important with regard to data quality. However, methods for adequate severity assessment, especially considering pain, are rather rare regarding large animal models. Therefore, in the present study, accompanying a surgical pilot study, telemetry and the Sheep Grimace Scale (SGS) were used in addition to clinical scoring for severity assessment after surgical interventions in sheep. METHODS: Telemetric devices were implanted in a first surgery subcutaneously into four German black-headed mutton ewes (4-5 years, 77-115 kg). After 3-4 weeks of recovery, sheep underwent tendon ablation of the left M. infraspinatus. Clinical scoring and video recordings for SGS analysis were performed after both surgeries, and the heart rate (HR) and general activity were monitored by telemetry. RESULTS: Immediately after surgery, clinical score and HR were slightly increased, and activity was decreased in individual sheep after both surgeries. The SGS mildly elevated directly after transmitter implantation but increased to higher levels after tendon ablation immediately after surgery and on the following day. CONCLUSION: In summary, SGS- and telemetry-derived data were suitable to detect postoperative pain in sheep with the potential to improve individual pain recognition and postoperative management, which consequently contributes to refinement.

Inequality in urban green space benefits: Combining street greenery and park greenery.

In this paper, we measured the amount of urban green space (UGS), defined here as park greenery and street greenery, in the Guangzhou Beltway region using remote sensing image data and the green view index (GVI) based on human visual images. We also evaluated the benefits of UGS comprehensively considering park greenery and street greenery within the Guangzhou Beltway region. We then calculated the urban green space score (UGSS) by assessing the amount of street greenery and park greenery and then juxtaposing the score with the population distribution of the region. The results show inequities in the spatial distribution of UGSS values within the Guangzhou Beltway region. The benefit score of street greenery is low. The service area of parks can't cover the whole study area. The comprehensive benefit score of UGS is composed of two parts, the park greenery score and the street greenery score, but the spatial distribution of UGSS values remains uneven. The UGS benefits enjoyed by one-half of the population of the study area are low, and the UGSS values of the more densely populated areas are not high.

Costs and outcomes of mobile cardiac outpatient telemetry monitoring post-transcatheter aortic valve replacement.

Aim: To estimate the costs and outcomes of transcatheter aortic valve replacement (TAVR) recipients based on the use of mobile cardiac outpatient telemetry (MCOT) monitoring. Materials & methods: A retrospective database study was conducted to estimate costs, contribution margins (CMs), pacemaker insertions and other outcomes for patients undergoing TAVR procedures with MCOT monitoring post-procedure versus non-MCOT monitoring. Results: A total of 4164 patients were identified (283 MCOT monitoring and 3881 non-MCOT monitoring). The rate of pacemaker insertion following hospital discharge was higher in the MCOT cohort (6.6 MCOT vs 2.1% non-MCOT; p = 0.007). MCOT use was associated with lower costs and improved CMs of the index TAVR admission (costs: US$40,569 MCOT vs $43,289 non-MCOT; p = 0.003; CMs: US$7087 MCOT vs $5177 non-MCOT; p = 0.047) with no difference through the subsequent 60-day period following discharge. Conclusion: MCOT for ambulatory cardiac monitoring post-TAVR discharge is associated with higher rates of pacemaker insertion, at no overall greater costs.

Non invasive jacketed telemetry in socially-housed rats for a combined assessment of respiratory system, electrocardiogram and activity using the DECRO system.

Respiratory and cardiovascular systems are among the vital organ systems that should be studied in safety pharmacology core battery test. Non-invasive jacketed external telemetry technology that enables concomitant monitoring of both systems has been available and used widely for non-rodent species. Recently, the DECRO system, a miniaturized technology system in line with the "3Rs" principles, has been developed to provide a similar approach in rats. However, data to evaluate this system in socially-housed rats is lacking. Therefore, the objectives of this study were to determine the tolerability and the material integrity of this novel solution in pair-housed rats in two conditions: i) in a single session of 22 h simulating a stand-alone safety pharmacology study design, and ii) in three repeated sessions of 22 h each, simulating the inclusion of safety pharmacology endpoints in a 1-month toxicology study. In both conditions, the GABAB receptor agonist baclofen was used as a reference compound inducing cardiorespiratory changes. Our results provided evidence that this novel solution was well tolerated, the material was resistant to deterioration and that it allowed the accurate recording, in a non-invasive manner, of cardiorespiratory parameters and activity level in freely moving, pair-housed rats in the above two conditions. In addition, the expected respiratory depressant effects of baclofen were recorded. These results pave the way for considering this novel solution as an enhanced approach for nonclinical safety assessment in rats.

Nonclinical cardiovascular safety assessment of thioridazine: Impact of autonomic tone, body temperature, and choice of species.

Pending updates to ICH S7B/E14 guidelines will enable the substitution of human TQT studies with support from concomitant negative hERG and non-rodent CV studies. This retrospective analysis compared the effects of thioridazine (THD) (5-20 mg/kg) on heart rate (HR), blood pressure (BP), body temperature (Tc), and QT in the dog (n = 6), cynomolgus monkey (n = 4), and Goettingen minipig (n = 4) with data from previously completed studies employing crossover designs. As QT measurements are confounded by HR and Tc changes, QT effects were individually corrected for changes in HR (QTca) and Tc (QTcaT). THD-induced hemodynamic changes seen in humans were most accurately reflected in the monkey and, to a lesser extent, the dog, but not in the minipig. The minipig was most sensitive to THD QTc effects. When QTca was adjusted for THD-associated Tc decreases in minipigs and monkeys, the minipig revealed a lessened but pronounced QTcaT increase (48 ms). In the monkey, a persistent QTca increase was reduced to only a transient (0.5-3 h) QTcaT increase (20 ms). The dog's lack of THD QTca effects triggered co-administration of atenolol (AT) to attenuate THD-induced HR increases in the dog and monkey. THD + AT revealed peak QTcaT increases of 32 ms in the dog and 40 ms in the monkey, suggesting potential autonomic nervous system (ANS) interference in detecting repolarization changes. These results highlight critical species-specific differences in the outcome of parallel safety investigations. Species selection for nonclinical safety studies should consider the potential impact of Tc and ANS effects to avoid false-negative or overly positive outcomes.

Investigational New Drug Enabling Nonclinical Safety Pharmacology Assessment of the Iminosugar UV-4, a Broad-Spectrum Host-Targeted Antiviral Agent.

UV-4 (N-(9-methoxynonyl)-1-deoxynojirimycin) is a broad-spectrum antiviral drug candidate with demonstrated activity in vitro and in vivo against multiple, diverse viruses. Nonclinical safety pharmacology studies were conducted to support the filing of an Investigational New Drug (IND) application. Preliminary in vitro pharmacology testing evaluating potential for binding to "off-target" receptors and enzymes indicated no significant liability for advanced development of UV-4. The safety pharmacology of UV-4 was evaluated in the in vitro human ether-à-go-go-related gene (hERG) assay, in a central nervous system (CNS) study in the mouse (modified Irwin test), in a respiratory safety study in conscious mice using whole body plethysmography, and in a cardiovascular safety study in conscious, radiotelemetry-instrumented beagle dogs. There were no observed adverse treatment-related effects following administration of UV-4 as the hydrochloride salt in the hERG potassium channel assay, on respiratory function, in the CNS study, or in the cardiovascular assessment. Treatment-related cardiovascular effect of decreased arterial pulse pressure after 50 or 200 mg of UV-4/kg was the only change outside the normal range, and all hemodynamic parameters returned to control levels by the end of the telemetry recording period. These nonclinical safety pharmacology assessments support the evaluation of this host-targeted broad-spectrum antiviral drug candidate in clinical studies.

Evaluation of six methods for external attachment of electronic tags to fish: assessment of tag retention, growth and fish welfare.

External attachment of electronic tags has been increasingly used in fish studies. Many researchers have used ad hoc attachment methods and provided little or no validation for the assumption that tagging itself does not bias animal behaviour or survival. The authors compared six previously published methods for externally attaching acoustic transmitters to fish in a tank holding experiment with black sea bass Centropristis striata (L.). They tracked tag retention, fish growth and external trauma (as a measure of fish welfare) for 60 days. For each of these metrics, the results showed a wide range of responses among tagging treatments. A simple attachment method using a spaghetti tag passed through the dorsal musculature of the fish and tied to the end cap of the transmitter emerged as the preferred option based on high retention, no impact on growth and relatively low detriment to fish welfare. Future field studies using external electronic tagging should consider tag-related effects that could compromise results when selecting a method for tag attachment.

Food resources affect territoriality of invasive wild pig sounders with implications for control.

Interest in control methods for invasive wild pigs (Sus scrofa) has increased due to their range expansion, population growth, and an improved understanding of their destructive ecological and economic effects. Recent technological advances in traps for control of pig populations facilitate capture of entire social groups (sounders), but the efficacy of "whole-sounder" trapping strategies is heavily dependent on the degree of territoriality among sounders, a topic little research has explored. We assessed territoriality in wild pig sounders on the Savannah River Site, South Carolina, USA, and examined whether availability of food resources provided by a municipal-waste landfill affected among-sounder territoriality. We estimated utilization distribution overlap and dynamic interactions among 18 neighboring sounders around a landfill. We found that although neighboring sounders overlapped in space, intensity of use in shared areas was uniformly low, indicating territorial behavior. Neighbors tended to share slightly more space when closer to the landfill waste cells, indicating availability of a super-abundant resource somewhat weakens the degree of territoriality among sounders. Nevertheless, we conclude that sounders behaved in a generally territorial manner, and we discuss implications for whole-sounder trapping programs, particularly near concentrated resources such as landfills and crop fields.

Automated blood sampling in canine telemetry model: Enhanced assessment of immune liabilities.

INTRODUCTION: This manuscript presents a successful integration of multi-timepoint biomarker blood sampling (e.g., cytokines) in a conscious dog cardiovascular study using automated blood sampling via vascular access ports in telemetry instrumented dogs. In addition to determining plasma exposure of the test compound, the assessment of biomarkers of interest allows for more comprehensive preclinical evaluation on a traditional conscious dog cardiovascular (CV) telemetry study especially for immunology and immune-oncology molecules. This model system provides a rapid and efficient means to quickly gain understanding of potential effects on key cardiovascular parameters in large species that are commonly used for preclinical safety evaluations while collecting multiple blood samples for drug and cytokine analysis. METHODS: Male beagle dogs were chronically implanted with telemetry devices (PhysioTel™ model D70-PCTP) and vascular access ports (SPMID-GRIDAC-5NC). BASi Culex-L automated blood sampling (ABS) (Bioanalytical Systems, Inc) system was used to collect blood samples at multiple time points for cytokine analysis. Four beagles received low-dose lipopolysaccharide solution (LPS) (0.1 and 0.5 µg/mL). The following cytokines were measured by Milliplex® map Canine Cytokine Magnetic Bead Panel: Interleukin (IL) 2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, TNF-α, MCP-1, KC-like, GM-CSF, IFN gamma, and IP10. RESULTS: Low dose LPS administration induced a pronounced dose-dependent, transient release of key inflammatory cytokines (IL-2, IL-6, IL-10, TNF-α, MCP-1, and KC-like). Cytokine responses were similar to other canine and human endotoxin models. LPS administration led to an increase in body temperature, heart rate, and mean arterial pressure, as well as a decrease in QTcV interval. CONCLUSION: Successful incorporation of cytokine analysis in telemetry instrumented dogs with vascular access ports allows for translational PK/PD modeling of both efficacy and safety of compounds in the immunology as well as the immune-oncology therapeutic areas designed to modulate the immune system. Remote collection of blood samples simultaneously with CV endpoints is a significant enhancement for assessment of biomarkers that are sensitive to animal handling and excitement associated with room disturbances which are obligatory with manual blood collection. Furthermore, implementing this approach has also refined our animal welfare procedure by reducing the handling during a study and thereby reducing stress (positive refinement 3R impact).