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Introduction The treatment of burn injured patients requires accurate wound assessment to determine appropriate interventions. Clinical assessment of burn depth, even by experts in the field, has an accuracy of only 60–80%. The purpose of this study is to estimate the performance of burn wound assessment by burn care professionals from still images. Methods This was an IRB-approved prospective cohort study in which burn care providers used a tablet-based digital interface to answer a 10-item questionnaire and to identify non-healing burn wounds from 5 patients scenarios. Each wound was evaluated using a polygon software interface to mark non-healing regions within the wound. Each wound had a ground truth determined by a consensus panel of study investigators using still photograph at 21-days post-injury to discern healing and non-healing regions. A power analysis and sample size of 100 participants produced a two-sided 95% confidence interval with a width equal to 0.20 when the sample proportion is 0.60. Continuous variables were analyzed by mean, standard deviations, median and quartiles while categorical data was analyzed as exact number and percentage. Burn wound assessment performance metrics for the providers were calculated for the whole cohort and then for subgroups using point estimate at a pixel level. Accuracy, sensitivity, specificity, area positive predictive value (APPV), and area negative predictive value (ANPV) were calculated from the ground truth and participants selected regions of non-healing wounds. Results One hundred fifty-six healthcare providers enrolled (50 physicians, 14 APPs, 63 nurses, 24 therapists, and 5 paramedics) with 9.96 ± 9.49 mean years of experience and 70% employed at a verified burn center. All five regions were represented in the analysis (Eastern Great Lakes (4%), Midwestern (6.5%), Northeastern (22%), Southern (53.5%), and Western (14%). 29.3% of the participants selected “schedule for surgery” when reviewing images of wounds that healed without surgery. 28.7% of the participants selected, “local wound care no surgery needed or, “local wound care, reassess in 7+ days for possible surgery.” Performance measures were not associated with years of experience. Overall performance is available in Table 1. Conclusions Improving burn wound assessment performance could improve our use of limited resources in burn care by optimizing patient transfers/treatments and avoiding unnecessary surgeries. Our study expands upon prior work in the field and demonstrates that burn wound assessment has significant room for improvement. These findings open the proverbial door for diagnostic devices found in other fields of medicine and our partnership with emergency room providers to advance burn care. Applicability of Research to Practice More accurate wound assessment will lead to improved treatment and triage by EM and Burn practitioners.

Introduction An FDA-approved bioengineered allogeneic cellularized construct (BACC) provides burn surgeons with an alternative treatment for deep partial-thickness (DPT) burns and may reduce the need for autografting. A phase 3b, open-label, single-arm, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of BACC treatment in adults with DPT thermal burns containing intact dermal elements. Methods Patients aged ≥18 years with 3% to < 50% total body surface area of partial-thickness ± full-thickness thermal burns were enrolled. A single application of up to 1:1 meshed BACC was applied to ≤3 burn areas on the torso or extremities (≤2000 cm2 area of BACC). Patients were followed for 24 weeks. The primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Additional endpoints were patients and treatment sites with confirmed wound closure (complete re-epithelialization without drainage for 2 consecutive visits ≥2 weeks apart) of the BACC treatment site without autografting by Week 12; durable wound closure by Week 24; time to wound closure without autografting (determined by Kaplan-Meier estimate); scar evaluation using the Patient and Observer Scar Assessment Scale (POSAS); and patients with wound infection-related events. The sample was not designed or sized to determine efficacy. Results Overall, 52 patients were enrolled. Pruritus was the most frequently reported TEAE (n=22 [42.3%]). There were 2 (3.8%) BACC-related TEAEs; both were pruritus and mild in severity. There were 20 serious AEs in 10 (19.2%) patients; none were related to BACC. No patients discontinued the study due to TEAEs. There were 4 (7.7%) deaths (aspiration, myocardial infarction, self-injury, and Gram-negative rod sepsis); none were related to BACC. Wound infection-related events occurred in 5 (9.6%) patients. Overall, 46 (88.5%) patients and 87 (90.6%) BACC-treated wounds did not require autografting. Half of patients achieved wound closure by Week 5. At Weeks 12 and 24, observer and patient total POSAS scores (mean ± SD) were 18.7 ± 8.08 and 18.8 ± 9.84, and 24.5 ± 11.0 and 20.2 ± 12.5, respectively. Wound closure of the BACC treatment site without autografting Conclusions There were no unexpected wound or BACC-related events. The safety of BACC supported its prescribing information. Patients treated with BACC achieved durable wound closure without autografting and thus showed expected clinical benefit in this population. The use of BACC in DPT burns in this study was donor-site sparing. Applicability of Research to Practice Treatment with BACC may offer a promising alternative to autografting for DPT burns.

Introduction Based on studies showing the use of autologous skin cell suspensions (ASCS) leads to burn wound closure with significantly smaller amounts of harvested donor skin, the Food and Drug Administration approved the first ASCS for the reconstruction of thermal injuries in September, 2018. The benefit of needing less donor skin to heal a given soft tissue wound has led to off-label usage of ASCS in a variety of clinical situations, such as necrotizing soft tissue infections (NSTI), toxic epidermal necrolysis (TEN), and traumatic injuries with soft tissue loss among others. Here, we report on a single-institution case series of ASCS usage for closure of soft tissue wounds caused by nonthermal mechanisms. Methods We performed a retrospective chart review of all patients treated with ASCS for an indication of non-thermal soft tissue wounds at our American Burn Association-verified academic burn center between April 1, 2018 to June 1, 2022. Descriptive demographic data were collected. Results Eight patients (6 male/2 female, mean age 57 + 17 yrs, mean length of stay 46 + 30 days) were found to have undergone closure of their wounds using ASCS during the time period of the chart review. Indications were NSTI (n=2), frostbite (n=2), antiphospholipid syndrome (n=2), and TEN (n=2). ASCS was used as a sole therapy for the TEN patients while ASCS was used in combination with meshed autografting for all other patients. The mean size of wounds treated with ASCS was 2835 + 2670 cm2, and the mean ASCS take rate was 86 + 7%. No ASCS-related complications were found. Conclusions These results bolster the off-label use of ASCS solutions for closure of nonthermal wounds while the surgical world awaits the results of an ongoing Phase III trial on this question Applicability of Research to Practice This study seeks to contribute to the literature supporting off-label uses of ASCS in non-thermal injuries & diseases.

Introduction Burn centers serve an essential role in providing specialized care for the injured. Professional societies (verify) and state agencies (designate) these facilities through a process that evaluates the resources, processes, and capabilities of each burn center. Over 90% of the level 1 or 2 trauma centers in the US and only around 50% of burn centers are verified. The goal of our study was to evaluate the variability of verified and designated burn centers and trauma centers in the US. Methods The Databases for Optimal Resources for Injury Care (DORIC) is a centralized database developed by the American Hospital Association, American College of Surgeons Committee on Trauma, American Burn Association, all fifty US states’ Departments of Health, and claims databases through a collaboration with BData, LSUHSC, Spectral MD, and UNO. Categorical data was assessed using Fisher’s exact while continuous variables were assessed with paired t-test and confidence intervals. The analysis included hospital and burn ICU bed count, hospital revenue, ED visits, discharges, and urban vs rural geography. Results The database includes 134 burn centers of which 75 were verified (56%), 91% were in an urban setting and 87% were co-located with a trauma center. Hospitals had a median of 492 staffed beds, 79,449 ER visits, and 18,437 discharges. Burn centers had a median of 11 burn ICU beds and 3,285 hospital days/year. Urban vs rural geography was not different between verified and designated burn centers (p=0.54). All categories of revenue were associated with burn center verification. Conclusions Our study demonstrates no significant difference with the hospital size, location (urban vs rural), ER volume, hospital beds, or burn ICU beds. Significant differences were identified with the rate of discharge and revenues which could be attributed to services, quality, or reimbursement. Given that only half of burn care occurs at verified burn centers, additional research is needed to better understand these significant differences. Applicability of Research to Practice A keen understanding of burn center characteristics is essential to serve the burn professionals that work at burn centers and the communities they serve.

Introduction Adipose-derived stem cells (ADSCs) have an important role in the modulation of burned tissue repair through the release of paracrine factors that stimulate the wound healing response. In this study, we tested the hypothesis that smoking status alters the profile of paracrine factors secreted from ADSCs isolated from damaged adipose tissue. Methods Adipose tissue was collected from adult patients (N=8) with severe burn injuries ( >20% total body surface area) at the index operation. ADSCs were extracted and cultured in vitro. Supernatants were harvested 30 hours after plating and used for cytokine determinations by Multiplex assay. Fluorescence activated single cell sorting (FACS) confirmed their phenotype with markers CD 90, CD 166, and CD 73. Univariate analyses were performed to compare the two cohorts (Smokers vs non smokers). All outliers were removed. Results Higher amounts of anti-inflammatory cytokines IL-4(p=0.03) and IL-10(p=0.04) and pro-inflammatory cytokines TNF-alpha (0.03), IL-8, and IFN-gamma (p=0.03) were detected in burn patients who were current everyday smokers when compared to nonsmokers, or former smokers. No significant differences in supernatant concentrations of IL-17, IL-1 beta, TGF-alpha, IL-6, and IL-13 were observed (p >0.05). Mortality was higher in the smoker group when compared to non-smokers (p=0.02). Conclusions The results from this study suggest that smoking status in patients with a major burn injury may alter the profile of paracrine factors secreted from ADSCs, and on-going studies will increase sample size and refine experimental approach. Furthermore, these results support the need for studies examining the systemic effects of smoking status of patients suffering burn injuries impacts the wound healing. Applicability of Research to Practice Study the effects of smoking on wound healing in burn injuries.

Introduction Accurate clinical differentiation of deep partial-thickness (DPT) and full-thickness (FT) wounds is essential in justifying appropriate treatments for heterogeneous burns. Only recently has non-invasive burn depth imaging been ground-truthed with tissue punch biopsies; an endeavor that will no doubt improve AI imaging algorithms in the near future. Prior literature supports unique apoptotic and necrotic properties of DPT and FT wounds, suggesting a use for not only standard stains (H&E), but apoptotic marker staining in assisting clinical diagnosis of burn depth, progression and/or conversion. Methods The aim of this study was to evaluate the presence of apoptotic cells in DPT and FT samples previously diagnosed by a burn biopsy algorithm (BBA-V2) for burn depth and severity by expert review of H&E-stained slides. Eight paired biopsies were collected from DPT and FT wounds in four patients within 72 hours of thermal injury and were immunofluorescently labeled for apoptosis markers by detection of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and cleaved caspase-3 (CC-3) staining. Fluorescence intensity in dermal appendages within images was used to quantify signal at 40x magnification for CC-3. % positive TUNEL cells were graded by an investigator blinded to the burn severity. A higher grade indicated higher % positivity. TUNEL grading was evaluated by Chi square test. CC-3 intensity was evaluated by Student’s t-test. Results Across all four patients, FT burns had higher levels of CC-3 in dermal appendages compared to DPT burns (Cy3:DAPI ratios: 1.53 ± 0.28 vs. 0.75 ± 0.13; p=0.1074). Within each patient, all FT biopsy sites had significantly higher levels of CC-3 versus DPT biopsy sites (p< 0.05)(Table). DPT burns had a greater proportion of patients with increasing grades of TUNEL positive cells (DPT: Grade 1: 16%, Grade 2: 36%, Grade 3: 48%; FT: Grade 1: 42.3%, Grade 2: 23.1%, Grade 3: 34.6%, p=0.1178). Conclusions CC-3 and TUNEL levels within dermal appendages align with burn depth classification by H&E staining, wherein appendages graded as necrotic had higher levels of CC-3 and lower levels of TUNEL. Therefore, CC-3 and TUNEL are potential secondary histological markers for burn depth. Further analysis of isolated, individual dermal appendages is underway to identify what additional information this secondary marker may add to the diagnosis of burn depth. Applicability of Research to Practice For the first time there is access to a large tissue repository of biopsies from burn wounds. Although staining from these samples has been used to build diagnosis algorithms with success, much more can be learned from the cellular pathophysiology when secondary analyses are performed. These assays may help us understand the processes of burn conversion.

Introduction Disaster planning and preparedness for a Burn Mass Causality Incident (BMCI) must consider both worst-case scenarios as well as most likely events that could strain a burn center (BC) resources. This study evaluates the growing threat of utilizing fire as a weapon for terrorist attacks and criminal acts in the United States. Methods Statistics regarding the use of fire as a weapon over a 2-year period were reviewed and summarized along with a review of significant events over 30 years. In addition, data regarding the type of weapon used in these attacks, intended target, and motives were collected and compared. Results According to the Cyber Security and Infrastructure Security Agency (CSISA), incidents related to arson or fire as a weapon in the US increased by 56.9% in cities with populations over 1 million people between 2019 and 2020 and 11.3% in towns with populations under 10,000. In addition, improvised Incendiary Device (IID) incidents increased by 210% at government facilities, 113% at commercial facilities, and 114% at critical infrastructure facilities during the same time frame. Conclusions The US continues to face complex and evolving threats from extremists, criminals, and terrorists. Methods have included attacks utilizing arson, IIDs, deliberate forest fires, and more. Assailants have used fire as a weapon to target public gatherings, individuals, and government property and as a component of complex coordinated attacks. These attacks have resulted in both large numbers of fatalities and burn injuries. The materials required to create a weapon utilizing fire are cheap, readily available, and require no formal training. Applicability of Research to Practice Criminal or terrorism-related incidents involving the use of fire as a weapon can result in mass causality events with large numbers of burn patients. These incidents can potentially overwhelm both first responders and local BC quickly. Therefore, BCs must have an updated disaster plan that has been evaluated and communicated with local fire and EMS, neighboring hospitals, and regional BCs.

Introduction Only 2% of US hospitals have designated burn centers (BC), of which 57% are verified by the American Burn Association (ABA). Further, of the non-verified burn centers, it is unclear which ones meet requirements set by their state departments of health. This gap in knowledge of BC verification and/or designation status combined with the lack of an accurate, publicly available database to route patients and characterize BC resources creates challenges in burn care, especially in disaster preparedness. The goal of our study was to characterize the net effect of domestic BC openings and closings over the last decade on US burn resources and, thus, access to care. Methods Our group has recently created the National Injury Resource Database (NIRD), a comprehensive list of every US Level I and II trauma center and/or burn center. NIRD was created by culling these facilities from 1) the current ABA burn center directory, 2) the current ABA burn center regional map, 3) the American Hospital Association database, 4) the American College of Surgeons Committee on Trauma database, and 5) data from all 50 State Departments of Health. Redundant entries were omitted, and 100% of the remaining institutions were then personally contacted by one of the study investigators to confirm or clarify the status of each center as well as the resources listed in the various databases. The NIRD database was then compared to the ABA’s 2012 burn center directory to compare the number, identities, and characteristics of those US BCs which had either closed or opened in the intervening ten years. Results In 2012, there were 127 total BC, 63 of which were ABA verified. Currently, NIRD shows that there are 134 total BC recognized by the ABA, 76 of which are verified. Since 2012, 11 BC have been removed from the ABA’s burn center directory after either closing or failing to maintain ABA recognition, while 18 BC have been added. In the same time frame, there have been changes in BC verification status across the US, with 14 BC gaining ABA verification and 1 BC losing verification. In comparing the ABA’s current BC directory to their burn center regional map, we found variability in 18 centers across 15 states (CA, DC, IL, IN, KS, MD, ME, MI, MS, MO, NY, TN, TX, VA, VT), i.e., instances in which 1 or more BC found on the ABA’s BC regional map were not found on the ABA’s BC directory list. Conclusions The last 10 years have shown an upward trend in the number of US BC. Further, we found variability in the ABA’s online resources in 15 states, suggesting that their resources are outdated. NIRD can serve as a resource for the construction of publicly available real-time tools to aid in routing burn patients. Applicability of Research to Practice NIRD can serve as a resource for the construction of publicly available real-time tools to aid in routing burn patients.

Integration of advanced practitioners (APs) into academic medical centers can improve processes of care and decrease physician workload but may adversely impact general surgery residency training. The aim of the present study was to characterize general surgery resident perceptions of APs and their impact on resident training. We conducted an institutional review board-approved survey covering five topic areas: knowledge of AP training, interaction with APs, scope-of-practice of APs, role of APs in the health-care team, and impact of APs on physician training. The survey was administered to general surgery residents at six large academic medical centers. One hundred eighteen general surgery residents completed the survey. The majority (43.6%) of respondents were junior residents. All respondents had interactions with APs with 90.7 per cent having worked directly with an AP in the last month. Residents reported minimal formal educational involvement by APs with 6.8 per cent reporting participation in didactics and 22.2 per cent teaching operative techniques. Almost half (44.1%) of the respondents reported that APs played an important role in their education, and 42.4 per cent of respondents disagreed or strongly disagreed that the role of the AP is well defined in their hospital. Today's general surgery residents work closely with APs who seem to positively impact resident education. Although residents perceive significant benefit with integration of APs, well-defined roles are lacking.

Biopharmaceutical manufacturers rely on consumable materials to manufacture their drug products. Along with the benefits of these consumables come attendant risks, one being an interruption to their supply chain. This risk may be actively managed through the institution of a security of supply program. This chapter discusses four main elements to supply security: material selection, supplier selection, risk management, and communication. It explores considerations for three consumable segments: single-use manufacturing equipment, cell culture media, and chromatography resins.

This paper presents a comparative study of electromagnetic performance and power losses of a high-speed surface-mounted permanent magnet (SPM) machine supplied by a pulse-width modulation (PWM) and pulse-amplitude modulation (PAM), also known as quasi-square wave modulation (QSM). In the simulation the inverter is operated at different DC-bus voltage levels and different modulation indices, i.e. amplitude and frequency, for the PWM. The analysis is achieved using circuit simulation of the inverter linked with a 2D-finite element analysis (FEA) of the machine. The comparison focuses on the phase current and voltage, and distortion of the torque waveforms and the core, rotor and inverter losses. It is found that, at higher DC-bus voltage, higher phase current distortion is found and consequently higher torque ripple and induced harmonics in the rotor loss. Moreover, similar effect is found when higher amplitude modulation index is applied. Furthermore, higher frequency modulation index results in lower phase current harmonics and hence lower torque ripple and rotor loss however, this comes at the expense of the inverter loss.

Membrane adsorbers provide an attractive alternative to traditional bead-based chromatography columns used to remove trace impurities in downstream applications. A linearly scalable novel membrane adsorber family designed for the efficient removal of trace impurities from biotherapeutics, are capable of reproducibly achieving greater than 4 log removal of mammalian viruses, 3 log removal of endotoxin and DNA, and greater than 1 log removal of host cell protein. Single use, disposable membrane adsorbers eliminate the need for costly and time consuming column packing and cleaning validation associated with bead-based chromatography systems, and minimize the required number and volume of buffers. A membrane adsorber step reduces process time, floor space, buffer usage, labor cost, and improves manufacturing flexibility. This "process compression" effect is commonly associated with reducing the number of processing steps. The rigid microporous structure of the membrane layers allows for high process flux operation and uniform bed consistency at all processing scales.

This essay presents a methodological framework for the comparative study of religion by analyzing academic description and explanation. It demonstrates how these two methods are in fact different forms of comparison with distinct goals and objectives. It further argues that description and explanation are related according to Bertrand Russell's theory of logical types and that successful comparative study adheres to the principles of logical typing. The essay aims to encourage more confident comparative studies in the History of Religions.

By use of a survey that assessed practice patterns and responses to case vignettes of anxiety and depression in the medically ill, 38 psychiatrists were compared with 10 national leaders in consultation-liaison psychiatry. On the case vignettes, percentage agreement with the experts varied significantly by case and by question. Fifty-eight percent of the time the psychiatrists agreed with the experts on whether to order laboratory tests as compared with an 81% agreement level on whether to use psychotherapy. Multiple regression analysis revealed that the best model to predict lower agreement with the experts was years in practice plus percentage of time spent in solo (vs. group) practice (r 2 = 0.40). This study extended previous data-based pharmaco-epidemiology by assessing multiple aspects of psychiatrists’ practice patterns. Psychiatrists who are more distant from training years and more isolated from the current stimulation of colleagues may be particularly appropriate targets for continuing education

Single-use biopharmaceutical manufacturing requires monitoring of critical manufacturing parameters. However, the lack of reliable single-use sensors prevents the biopharmaceutical industry from fully embracing single-use biomanufacturing processes. We report an approach for temperature-independent pressure sensing in single-use bioprocess components using passive radio-frequency identification (RFID) sensors. An RFID pressure sensor is fabricated by applying a pressure sensitive flexible membrane to an RFID-tag-based transducer and a layer that modulates the electromagnetic field (EMF) generated in the RFID sensor antenna. The sensor signal is modulated upon pressure-induced flexing of the membrane, providing a desired quantitative response of pressure of the fluid during the operation of the single-use component. We demonstrate a temperature-independent RFID pressure sensor that was tested to measure pressures from −5 to 33 psi with the ± 0.25 psi accuracy after gamma irradiation. Temperature-independent pressure response is provided from the multivariate analysis of the measured impedance of the sensor.

Single-use biopharmaceutical manufacturing requires monitoring of critical manufacturing parameters. We have developed an approach for passive radio-frequency identification (RFID)-based sensing that converts ubiquitous passive 13.56 MHz RFID tags into inductively coupled sensors. We combine several measured parameters from the resonant sensor antenna with multivariate data analysis and deliver unique capability of multiparameter sensing and rejection of environmental interferences with a single sensor. We demonstrate here the integration of these RFID sensors into single-use biopharmaceutical manufacturing components. We have tested these sensors for over 500 h for measurements of temperature and solution conductivity with the accuracy of 0.1°C (32-48°C range) and accuracy of 0.3-2.9 mS/cm (0.5-230 mS/cm range). We further demonstrate simultaneous temperature and conductivity measurements with an individual RFID sensor with the accuracy of 0.2°C (5-60°C range) and accuracy of 0.9 mS/cm (0.5-183 mS/cm range). Developed RFID sensors provide several important features previously unavailable from other single-use sensing technologies such as the same sensor platform for measurements of physical, chemical, and biological parameters; multi-parameter monitoring with individual sensors; and simultaneous digital identification.

Single-use biopharmaceutical manufacturing requires monitoring of critical manufacturing parameters. However, the lack of reliable single-use sensors prevents the biopharmaceutical industry from fully embracing single-use biomanufacturing processes. We report here an approach for passive radio-frequency identification (RFID)-based sensing that does not rely on costly proprietary RFID memory chips with an analog input but rather implement ubiquitous passive 13.56 MHz RFID tags as inductively coupled sensors with 16-bit resolution provided by a sensor reader. Developed RFID sensors combine several measured parameters from the resonant sensor antenna with multivariate data analysis and deliver unique capability of multiparameter sensing and rejection of environmental interferences with a single sensor. In this study we are integrating these RFID sensors into single-use biopharmaceutical manufacturing components such as buffer bags. Performance of these sensors for simultaneous solution conductivity and temperature sensing is discussed.

The single-use bioprocessing is an attractive new approach of biopharmaceutical manufacturing. Digital identification of single-use bioprocess components is critical to facilitate their asset management, to document electronic pedigree, and to provide authentication. This identification can be achieved using radio frequency identification (RFID) tags. In this study, we critically analyze the challenges for the gamma-sterilizable RFID tag technology to retain the reliable read/write ability of the tags after their gamma irradiation. In RFID tags, the gamma radiation induced loss of device performance (i.e. the ability to reliably write and read data from an integrated circuit (IC) memory chip) originates from two independent sources such as (1) radiation effects on the non-charge-based storage memory material and (2) radiation effects on the performance of analog and digital circuit components of an IC memory chip device. Our interdisciplinary knowledge of product design, analytical instrumentation, RF engineering, and Six Sigma statistics has resulted in the design and implementation of the tag interrogation concept that insures the high reliability of tag read/write after the gamma irradiation.

Mammalian cell-expressed therapeutic proteins are particularly vulnerable to contamination by endogenous retrovirus-like particles (RVLPs). The Viresolve NFR filter was designed to meet the critical requirement of manufacturing a safe and virus-free therapeutic by retaining RVLPs by a minimum of six log reduction value (LRV). The NFR designation refers to retrovirus removal in a normal flow format. To qualify the product, we tested two model viruses: the 78 nm diameter phi6 bacteriophage and the 80-110 nm diameter Xenotropic Murine Leukemia Virus (X-MuLV). Robust retention was demonstrated over a wide range of process parameters. Viresolve NFR filters also retain other model adventitious viruses including 70-85 nm diameter Reovirus 3 (Reo3), 70-90 nm diameter Adenovirus 2 (Ad2), and 53 nm diameter PR772 by >6 LRV. In addition to these model viruses, the filter retains >7 LRV of both the mycoplasma Acholeplasma laidlawii and the bacterium Brevundimonas diminuta. Protein passage is shown to be consistently high (95-100%) for a variety of therapeutic protein products, including monoclonal antibodies. Characterization of the filter in specific applications is made simple by availability of ultralow surface area (5 cm(2)) disks, which are shown to scale linearly to the manufacturing scale pleated-filters. Viresolve NFR filters provide consistent water permeability performance (34-37 LMH/psi) and show very little plugging for all feedstocks evaluated. The Viresolve NFR filter incorporates Retropore, a unique asymmetric polyethersulfone membrane, the surface of which has been modified to minimize protein binding.

The problem this Phase 2 SBIR effort addressed was the absence of an established, standard intermediate form (IF) for the exchange of VHDL encoded electronic data among CAD systems. This absence has severely constrained basic research environments, and has precipitated the current sub-optimal nature of CAD in VHDL tool development. Our Baseline Program developed this standard intermediate form (IF), as well as a VHDL design environment utilizing it, which is provided to the research community at no cost, and to commercial developers or users under a licensing fee. The SAVANT environment consists of an Analyzer (implementing the IF), a Code Generator, and a System Support Environment (SSE) containing debugger and visualization/analysis tools (called the VHDLyzer Toolkit or VTK). An option task implemented Object Oriented Extensions to VHDL in the SAVANT environment, and assessed their utility and effectiveness. The Phase 2 baseline objectives focused upon developing and validating the SAVANT system (analyzer, code, generator, debugger, visualization tools), and commercializing the resultant technology. The option task objectives addressed implementation of O-O VHDL constructs in SAVANT, and subsequent model selection, implementation and assessment of O-O VHDL performance in the SAVANT environment. All baseline and option task objectives were achieved, except for commercialization. which was partially achieved.

The lack of reliable single-use sensors prevents the biopharmaceutical industry from fully embracing single-use biomanufacturing processes. Sensors based on the same detection platform for all critical parameters in single-use bioprocess components would be highly desirable to significantly simplify their installation, calibration and operation. We review here our approach for passive radio-frequency identification (RFID)-based sensing that does not rely on costly proprietary RFID memory chips with an analog input but rather implements ubiquitous passive 13.56 MHz RFID tags as inductively coupled sensors with at least 16 bit resolution provided by a sensor reader. The developed RFID sensors combine several measured parameters from the resonant sensor antenna with multivariate data analysis and deliver unique capability of multiparameter sensing and rejection of environmental interferences with a single sensor. This general sensing approach provides an elegant solution for both analytical measurement and identification and documentation of the measured location.