Meeting Report of the 35th Annual Meeting of the Academy of Surgical Research: Summary of Presentations, Labs, and Workshops, Focusing on Experimental Surgery, Clearwater Beach, FL, 25-27 September 2019.

The 35th Annual Meeting of the Academy of Surgical Research took place in Clearwater Beach, Florida on 25-27 September 2019. This meeting brings together the experimental surgery community to share the latest in research and surgical techniques and fosters professional development through education, training, and certification. The Academy is made up of a diverse group of technicians, veterinarians, medical doctors, and biomedical researchers from industry, academia, and complimentary disciplines supporting discovery and translational research. Over 165 participants from 30 different states and 6 countries were in attendance for the scientific program and social events. Four keynotes were presented together with breakout and poster session tracks. Participants were able to work on applied skills in practical courses that included hands-on surgical technique wet-labs complimented with dry-lab suture technique and surgical anesthesia, plus workshops and roundtables focused on improving study design and publication best practices. Attendees were able to enjoy sun and fun while connecting with potential mentors and collaborators during the social program. We present the highlights from this meeting in this report together with selected abstracts that illustrate the diverse scientific expertise of the Academy and promising new surgical research.

Production of high-fidelity electropherograms results in improved and consistent DNA interpretation: Standardizing the forensic validation process.

Samples containing low-copy numbers of DNA are routinely encountered in casework. The signal acquired from these sample types can be difficult to interpret as they do not always contain all of the genotypic information from each contributor, where the loss of genetic information is associated with sampling and detection effects. The present work focuses on developing a validation scheme to aid in mitigating the effects of the latter. We establish a scheme designed to simultaneously improve signal resolution and detection rates without costly large-scale experimental validation studies by applying a combined simulation and experimental based approach. Specifically, we parameterize an in silico DNA pipeline with experimental data acquired from the laboratory and use this to evaluate multifarious scenarios in a cost-effective manner. Metrics such as signal1copy-to-noise resolution, false positive and false negative signal detection rates are used to select tenable laboratory parameters that result in high-fidelity signal in the single-copy regime. We demonstrate that the metrics acquired from simulation are consistent with experimental data obtained from two capillary electrophoresis platforms and various injection parameters. Once good resolution is obtained, analytical thresholds can be determined using detection error tradeoff analysis, if necessary. Decreasing the limit of detection of the forensic process to one copy of DNA is a powerful mechanism by which to increase the information content on minor components of a mixture, which is particularly important for probabilistic system inference. If the forensic pipeline is engineered such that high-fidelity electropherogram signal is obtained, then the likelihood ratio (LR) of a true contributor increases and the probability that the LR of a randomly chosen person is greater than one decreases. This is, potentially, the first step towards standardization of the analytical pipeline across operational laboratories.

Antiviral Activity of TMC353121, a Respiratory Syncytial Virus (RSV) Fusion Inhibitor, in a Non-Human Primate Model.

BACKGROUND: The study assessed the antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a preclinical non-human primate challenge model with a viral shedding pattern similar to that seen in humans, following continuous infusion (CI). METHODS: African green monkeys were administered TMC353121 through CI, in 2 studies. Study 1 evaluated the prophylactic and therapeutic efficacy of TMC353121 at a target plasma level of 50 ng/mL (n=15; Group 1: prophylactic arm [Px50], 0.033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 24 hours pre-infection to 10 days; Group 2: therapeutic arm [Tx50], 0.033 mg/mL TMC353121 from 24 hours postinfection to 8 days; Group 3: control [Vh1] vehicle, 24 hours post-infection to 8 days). Study 2 evaluated the prophylactic efficacy of TMC353121 at target plasma levels of 5 and 500 ng/mL (n=12; Group 1: prophylactic 5 arm [Px5], 0.0033 mg/mL TMC353121, flow rate 2.5 mL/kg/h from 72 hours pre-infection to 14 days; Group 2: prophylactic 500 arm [Px500], 0.33 mg/mL TMC353121; Group 3: control [Vh2] vehicle, 14 days). Bronchoalveolar lavage fluid and plasma were collected every 2 days from day 1 postinfection for pharmacokinetics and safety analysis. FINDINGS: TMC353121 showed a dose-dependent antiviral activity, varying from 1 log10 reduction of peak viral load to complete inhibition of the RSV replication. Complete inhibition of RSV shedding was observed for a relatively low plasma exposure (0.39 µg/mL) and was associated with a dose-dependent reduction in INFγ, IL6 and MIP1α. TMC353121 administered as CI for 16 days was generally well-tolerated. CONCLUSION: TMC353121 exerted dose-dependent antiviral effect ranging from full inhibition to absence of antiviral activity, in a preclinical model highly permissive for RSV replication. No new safety findings emerged from the study.

Cardiorespiratory safety evaluation in non-human primates.

INTRODUCTION: This study was designed to provide a comprehensive nonclinical respiratory safety pharmacology assessment using respiratory inductance plethysmography (RIP) concomitant with a standard cardiovascular (CV) safety assessment in non-human primates (NHP) in a single cardiorespiratory study. METHODS: RIP calibration data were generated in conscious, ketamine-sedated, or propofol-anesthetized NHP to determine the most appropriate method. Calibration accuracy was assessed using a CO(2) rebreathe maneuver. Regardless of the technique, the RIP system reliably demonstrated accurate assessment of the CO(2) rebreathe response when expressed as a percent change with respect to control. Four male NHP were given single oral doses of vehicle, 1.25 and 5 mg/kg test article followed by 20 mg/kg repeatedly for 7 days. Telemetry-derived cardiovascular parameters (PR, QRS, QT, heart rate corrected QT (QTcR) intervals, blood pressure [BP], and heart rate [HR]) and RIP-derived respiratory parameters (respiration rate [RR], tidal volume [TV], and minute volume [MV]) were determined for 24 h pretest, 2 h predose and 24 h postdose. RESULTS: A single dose of the test article at 5 or 20 mg/kg was associated with slight increases in HR, BP, RR, and MV at 2 to 7 h postdose, followed by decreases in HR, RR, TV, and MV at 5-23 h postdose. Decreases in HR, RR, TV, and MV were observed following 7 days of dosing at 20 mg/kg. Slight QTcR prolongation at 1 to 11 h postdose was observed following a single dose of 20 mg/kg. CONCLUSION: These data show that the integrated assessment of cardiovascular and respiratory parameters in NHP is achievable continuously for at least 24 h postdose. The use of RIP as a method to assess the effects of a novel compound on the respiratory system complements, but does not interfere with, the cardiovascular assessment of new drugs.

Capital planning for operating theatres based on projecting future theatre requirements.

During 2006, NSW and ACT Health Departments jointly engaged KPMG to develop an Operating Theatre Requirements' Projection Model and an accompanying planning guideline. A research scan was carried out to identify drivers of surgical demand, theatre capacity and theatre performance, as well as locating existing approaches to modelling operating theatre requirements for planning purposes. The project delivered a Microsoft Excel-based model for projecting future operating theatre requirements, together with an accompanying guideline for use of the model and interpretation of its outputs. It provides a valuable addition to the suite of tools available to Health staff for service and capital planning. The model operates with several limitations, largely due to being data dependent, and the state and completeness of available theatre activity data. However, the operational flexibility built into the model allows users to compensate for these limitations, on a case by case basis, when the user has access to suitable, local data. The design flexibility of the model means that updating the model as improved data become available is not difficult; resulting in revisions being able to be made quickly, and disseminated to users rapidly.

Projecting subacute inpatient activity in New South Wales.

We describe the development of a method for estimating and modelling future demand for sub- and non-acute inpatient activity across New South Wales, Australia to 2016. A time series linear regression equation was used, which is consistent with projection models found in the literature. Results of the modelling indicated an increase in rehabilitation, palliative care and maintenance episodes and bed-days. Projections for other categories of care are problematic due to smaller levels of activity and data quality issues. This project indicated a need for ongoing monitoring of type-changing by facilities and management of data quality. Local planners will need to consider a range of factors when considering the applicability activity projections at a local level, particularly within the specific age and clinical groupings.

Estimating and projecting subacute care demand: findings from a review of international methods.

A review of projection methodologies used to project sub-acute inpatient activity in various international health care jurisdictions was undertaken as part of a project to develop subacute inpatient activity projections for the state with the largest population in Australia. The literature search identified nearly 200 articles and found three main groups of projection methodologies: projections with a focus on subacute care; projections with a focus on acute care, but which often included subacute activity in the overall projections; and projections of specific diseases/conditions influencing the demand for subacute care. In terms of the examples in the literature specifically regarding subacute care, the most common method of estimating current or future need was the use of normative benchmark ratios of beds to population. This was mainly to provide a policy basis to encourage development of subacute services, but also because of convenience. In the literature regarding acute activity projection methodologies, many incorporated subacute activity in the overall activity measures of the acute hospital unit. The most common method of acute care activity projection was use of current or trended utilisation rates applied to population projections. It appears that a significant amount of planning and demand projection being undertaken internationally on subacute care takes place within acute care methodologies. In regard to the potential use of specific diseases/conditions that drive demand for subacute care, such as stroke or cancer, it is suggested that the best use of these disease-specific projections is in reality testing the results of other modelling. A number of conclusions are made and issues highlighted regarding projections of subacute inpatient activity.

Projected acute inpatient activity in New South Wales - aIM2005.

OBJECTIVES: To describe the statewide projections of acute inpatient activity in New South Wales. METHODS: Data on acute inpatient activity in NSW for the period 1998-1999 to 2003-04 were derived from the Admitted Patient Data Collection. Regression analysis was used to project trends in utilisation and length of stay by age group, clinical specialty groups and stay type (day-only and overnight). The projected separation rates and length of stay were subject to clinical review. Projected separation rates (by age group, clinical speciality and stay type) were applied to NSW population projections to derive the projected number of separations. Bed-days were calculated by applying projected overnight average length of stay. RESULTS: Total acute inpatient activity in NSW public hospitals is projected to increase from around 1.05 million separations in 2004 to around 1.3 million separations by 2017 (24%). Same-day separations are projected to increase from around 368 000 to around 514 000 (40%). Overnight separations are projected to rise from around 690 000 in 2003-04 to around 798 000 in 2016-17 (18%). Overnight bed-days are projected to increase from around 3.7 million in 2003-04 to around 4.1 million bed-days in 2017 (12%). Differences across age groups and clinical specialties are also evident from the modelling.