Enhancing Partner Nation Security: A Mixed-Methods Evaluation of A Peacekeeping Public Health Capacity Building Initiative.

INTRODUCTION: One way the U.S. Department of Defense (DoD) works to achieve national security is through security cooperation, by way of building and enhancing partner nation capacity. This study evaluated a health-related security cooperation training initiative delivered by the DoD to military peacekeepers. The study specifically examined outcomes of change, including the beginning phase of sustainability. MATERIALS AND METHODS: The U.S. DoD employed a train-the-trainer model in Ghana, Rwanda, Senegal, and Uganda to support the African Peacekeeping Rapid Response Partnership program. U.S. instructors trained 192 peacekeepers through 11 training iterations between December 2016 and March 2020. A mixed-method explanatory sequential design was used to explore training outcomes. Quantitatively, three hypotheses were tested using nonparametric statistical analysis. Qualitative analysis of documents was used to inform and contextually understand the quantitative results. This study was submitted to the George Washington University Institutional Review Board and was fully approved (NCR202918). RESULTS: Quantitative and qualitative results indicated improved short-term public health knowledge and upskill among partner nation participants. There was the beginning of a cascade effect of the partner nations' ability to autonomously teach tasks and skills to their military to sustain the initiative. Differences in achieving and maintaining change outcomes were related to student characteristics, the training course, and the partner nation. CONCLUSIONS: This research serves as the first published study to empirically examine health-related security cooperation train-the-trainer initiative change outcomes. This research is an essential building block to empirically evaluate and capture change outcomes from security cooperation capacity building training initiatives. The findings and recommendations inform security cooperation policy and associated investments.

Thawed solvent/detergent-treated plasma demonstrates comparable clinical efficacy to thawed plasma.

BACKGROUND: Thawed Plasma (TP), plasma thawed and refrigerated for up to 5 days, is a commonly transfused plasma product. This pilot study was conducted to determine whether Thawed Solvent/Detergent-treated Plasma stored refrigerated for up to 5-days post-thaw (T-S/D) was as efficacious as TP. STUDY DESIGN AND METHODS: This single institution retrospective cohort analysis evaluated the efficacy of T-S/D in reversing coagulopathies in comparison to TP. Utilizing the institution's electronic medical records, transfusion data were collected in adult patients who received either TP or T-S/D. The primary outcome was the incidence of subsequent transfusions within 24 hours after first dose of either type of plasma. Secondary outcomes included the number of blood products transfused within 24 hours of first-dose plasma, correction of pre-transfusion coagulation laboratory values, volume transfused, and clinical outcomes. RESULTS: TP was received by 301 patients and 137 received T-S/D during the first 32 months post-implementation of T-S/D. There was no difference in incidence of subsequent transfusions or number of blood products given. The median pre-INR of both the TP and T-S/D cohorts was 1.9, with a similar decrease in INR of 0.2 and 0.3 (p = 0.36), respectively, post plasma transfusion. There was no difference in correction of PT/aPTT, mortality, transfusion reactions, readmission rates, length of stay, or inpatient deep venous thrombosis. The median volume of T-S/D plasma transfused for the first dose was 126 mL less than TP (p = .0001). CONCLUSION: T-S/D was as efficacious as TP for the treatment of coagulopathies and the reversal of coagulation laboratory values.

The impact of Daratumumab on transfusion service costs.

BACKGROUND: Daratumumab (DARA) is a human IgG1κ monoclonal antibody directed against CD38, approved for the treatment of multiple myeloma. As CD38 is expressed on RBCs, DARA can interfere with pretransfusion testing. DARA interference can be negated by denaturation of CD38 on RBCs with dithiothreitol (DTT) reagents. Because of this interference in pretransfusion testing, our hospital implemented a notification and testing/transfusion algorithm (NATTA) for pretransfusion testing and RBC product provision for DARA patients. This standardized approach combines DTT-based testing with selective genotyping and the provision of phenotypically similar RBCs for patients with clinically significant antibodies. STUDY DESIGN AND METHODS: We evaluated pretransfusion test results and transfusion requirements for 91 DARA patients in an academic medical center over 1 year to determine the incremental cost of pretransfusion testing and RBC selection. The actual costs for the NATTA approach were compared to a theoretical approach using universal genotyping with a provision of phenotypically similar RBC transfusions. RESULTS: The annual cost of testing related to DARA after NATTA implementation was $535.76 per patient. The simulated annual cost for the alternative genotyping with provision of phenotypically similar RBC transfusions approach was $934.83 per patient. CONCLUSION: In our entire cohort of DARA patients, a DTT-based testing algorithm with selective genotyping and provision of phenotypically similar RBCs only for patients with clinically significant antibodies was less expensive than a simulated model of universal genotyping and provision of phenotypically similar RBCs.

Logistical and safety implications of temperature-based acceptance of returned red blood cell units.

BACKGROUND: AABB requires that red blood cells (RBCs) are maintained at 1 to 10°C during transport. Historically, blood banks used the 30-minute rule for returned RBCs transported outside of validated containers. The implications of this policy have not been previously reported in a real-life hospital setting. STUDY DESIGN AND METHODS: A 2-year, retrospective review of RBC units returned outside of qualified containers was conducted. During the first year, the 30-minute rule was used to accept RBCs back into inventory. Sequentially, the following year, a temperature-based approach was implemented using a thermometer with an accuracy of ±1°C. Time out of the blood bank, temperature upon return, wastage, and transfusion reactions associated with the reissued RBCs were analyzed. RESULTS: In our practice, the 30-minute rule would have accepted 15.2% of RBC units outside of the allowed temperature. Compared to the 30-minute rule, temperature-based acceptance was associated with a 13% increase in wastage (p < 0.001). During the 30-minute rule period, transfusion of returned and subsequently reissued RBCs was associated with a nonsignificant trend toward a higher transfusion reaction rate compared to the overall RBC transfusion reaction rate (1.4% vs. 0.6%, p = 0.084). During the temperature period, transfusion of returned and subsequently reissued RBCs had the same transfusion reaction rate compared to the overall RBC transfusion reaction rate (0.5% vs. 0.5%, p = 1.0). CONCLUSION: Temperature-based acceptance of returned RBCs is associated with significantly higher wastage compared to the 30-minute rule. A temperature-based acceptance practice mitigates the risk of accepting RBCs with unacceptable temperatures returned within 30 minutes of issue.

Assessment of Natural Variability of Maize Lipid Transfer Protein Using a Validated Sandwich ELISA.

Lipid transfer protein (LTP) is the main causative agent for rare food allergic reactions to maize. This paper describes a new, validated ELISA that accurately measures maize LTP concentrations from 0.2 to 6.4 ng/mL. The levels of LTP ranged from 171 to 865 µg/g of grain, a 5.1-fold difference, across a set of 49 samples of maize B73 hybrids derived from the Nested Association Mapping (NAM) founder lines and a diverse collection of landrace accessions from North and South America. A second set of 107 unique samples from 18 commercial hybrids grown over two years across 10 U.S. states showed a comparable range of LTP level (212-751 µg/g of grain). Statistical analysis showed that genetic and environmental factors contributed 63 and 6%, respectively, to the variance in LTP levels. Therefore, the natural variation of maize LTP is up to 5-fold different across a diverse collection of varieties that have a history of safe cultivation and consumption.

Analyzing pepsin degradation assay conditions used for allergenicity assessments to ensure that pepsin susceptible and pepsin resistant dietary proteins are distinguishable.

The susceptibility of a dietary protein to proteolytic degradation by digestive enzymes, such as gastric pepsin, provides information on the likelihood of systemic exposure to a structurally intact and biologically active macromolecule, thus informing on the safety of proteins for human and animal consumption. Therefore, the purpose of standardized in vitro degradation studies that are performed during protein safety assessments is to distinguish whether proteins of interest are susceptible or resistant to pepsin degradation via a study design that enables study-to-study comparison. Attempting to assess pepsin degradation under a wide-range of possible physiological conditions poses a problem because of the lack of robust and consistent data collected under a large-range of sub-optimal conditions, which undermines the needs to harmonize in vitro degradation conditions. This report systematically compares the effects of pH, incubation time, and pepsin-to-substrate protein ratio on the relative degradation of five dietary proteins: three pepsin susceptible proteins [ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco), horseradish peroxidase (HRP), hemoglobin (Hb)], and two pepsin resistant proteins [lipid transfer protein (LTP) and soybean trypsin inhibitor (STI)]. The results indicate that proteins susceptible to pepsin degradation are readily distinguishable from pepsin-resistant proteins when the reaction conditions are within the well-characterized optima for pepsin. The current standardized in vitro pepsin resistant assay with low pH and high pepsin-to-substrate ratio fits this purpose. Using non-optimal pH and/or pepsin-to-substrate protein ratios resulted in susceptible proteins no longer being reliably degraded by this stomach enzyme, which compromises the ability of this in vitro assay to distinguish between resistant and susceptible proteins and, therefore, no longer providing useful data to an overall weight-of-evidence approach to assessing safety of proteins.

One-step purification of phosphinothricin acetyltransferase using reactive dye-affinity chromatography.

Reactive dye purification is an affinity purification technique offering unique selectivity and high purification potential. Historically, purification of phosphinothricin acetyltransferase (PAT) has involved several steps of precipitation and column chromatography. Here, we describe a novel purification method that is simple, time-saving, inexpensive, and reproducible. The novel method employs a single chromatography step using a reactive dye resin, Reactive brown 10-agarose. Reactive brown 10 preferentially binds the PAT protein, which can then be specifically released by one of its substrates, acetyl-CoA. Using Reactive brown 10-agarose, PAT protein can be purified to homogeneity from E. coli or plant tissue with high recovery efficiency.

Using participatory action research to identify strategies to improve pandemic vaccination.

OBJECTIVE: Developing and implementing effective strategies to increase influenza vaccination rates among health care personnel is an ongoing challenge, especially during a pandemic. We used participatory action research (PAR) methodology to identify targeted vaccination interventions that could potentially improve vaccine uptake in a medical center. METHODS: Front-line medical center personnel were recruited to participate in 2 PAR teams (clinical and nonclinical staff). Data from a recent medical center survey on barriers and facilitators to influenza (seasonal, pandemic, and combination) vaccine uptake were reviewed, and strategies to increase vaccination rates among medical center personnel were identified. RESULTS: Feasible, creative, and low-cost interventions were identified, including organizational strategies that differed from investigator-identified interventions. The recommended strategies also differed by team. The nonclinical team suggested programs focused on dispelling vaccination-related myths, and the clinical team suggested campaigns emphasizing the importance of vaccination to protect patients. CONCLUSIONS: PAR methodology was useful to identify innovative and targeted recommendations for increasing vaccine uptake. By involving representative front-line workers, PAR may help medical centers improve influenza vaccination rates across all work groups.

Purification of phosphinothricin acetyltransferase using Reactive brown 10 affinity in a single chromatography step.

The expression of phosphinothricin N-acetyltransferase (PAT) protein in transgenic plants confers tolerance to the herbicide glufosinate. To enable the characterization of PAT protein expressed in plants, it is necessary to obtain high purity PAT protein from the transgenic grain. Because transgenically expressed proteins are typical present at very low levels (i.e. 0.1-50 µg protein/g grain), a highly specific and efficient purification protocol is required to purify them. Based on the physicochemical properties of PAT, we developed a novel purification method that is simple, time-saving, inexpensive and reproducible. The novel method employs a single chromatography step using a reactive dye resin, Reactive brown 10-agarose. Reactive brown 10 preferentially binds the PAT protein, which can then be specifically released by one of its substrates, acetyl-CoA. Using Reactive brown 10-agarose, PAT protein was purified to homogeneity from cottonseed with high recovery efficiency. As expected, the Reactive brown 10-produced PAT was enzymatically active. Other applications of the method on protein expression and purification, and development of PAT enzymatic inhibitors were also discussed.

Prevalence and factors associated with 2009 to 2011 influenza vaccinations at a university medical center.

BACKGROUND: Information on the rates and factors associated with influenza vaccinations, although limited, is important because it can inform the development of effective vaccination campaigns in a university medical center setting. METHODS: A study was conducted in 2011 to identify individual and organizational level barriers and facilitators to influenza vaccination among clinical and nonclinical personnel (N = 428) from a major university medical center. RESULTS: Seventy-one percent of clinical personnel (n = 170) reported pandemic H1N1 vaccination compared with 27% of nonclinical personnel (n = 258), even though vaccine was made widely available to all personnel at no cost. Similarly, disparate rates between clinical and nonclinical personnel were noted for the 2009/2010 seasonal influenza vaccine (82% vs 42%, respectively) and 2010/2011 combination (pandemic plus seasonal) influenza vaccine (73% vs 28%, respectively). Factors associated with pandemic vaccination in nonclinical personnel included the following: high level of influenza-related knowledge, concern regarding influenza contagion, history of previous influenza vaccinations or influenza illness, participation in vaccine-related training, and awareness of the institution's written pandemic plan. For clinicians, past history of seasonal influenza vaccination was associated with pandemic vaccination. For all participants, taking any 1 or more of the 3 influenza vaccines available in 2009 to 2011 was associated with intent to take a hypothetical future novel pandemic vaccine (odds ratio, 6.7; 95% confidence interval: 4.32-10.44; P < .001). CONCLUSION: Most of the risk factors associated with lack of vaccination uptake are amenable to organizational strategies.

National Cancer Institute's Small Grants Program for behavioral research in cancer control boosts careers for new investigators and fulfills NIH research priorities.

BACKGROUND: In 1998, the NIH's National Cancer Institute created the Behavioral Research Program (BRP) within the Division of Cancer Control and Population Sciences. A primary goal of the BRP is to stimulate and expand the field of behavioral research in cancer prevention and control. To help achieve this end, BRP created the Small Grants Program. This study examines the effect of the program on the careers of new investigators in cancer prevention and control. METHODS: A mixed-method analysis was conducted on data from a grantee survey and publication and post-award activity records. RESULTS: A majority of grantees (n=197) submitted additional research grant applications, and of these grantees, 37% (n=73) were awarded funding from the NIH and 20% (n=40) received funding at the R01 level. Grantees published research results in journals or presented at professional conferences. Of the 47 grantees who provided their curriculum vitae, 72% (n=34) published or had in press at least one article resulting from their small grant (R03) and 40% (n=19/47) published at least one article as lead author. These articles were cited a total of 134 times in 85 journals. CONCLUSIONS: By supporting investigators' initial behavioral research applications, the Small Grants Program seems to open the door to additional "independent" research opportunities and fulfills the NIH's goals of supporting early career investigators and stimulating promising new areas of cancer research.

Controlling the intracellular localization of fluorescent polyamide analogues in cultured cells.

The intracellular distribution of fluorescent-labeled polyamides was examined in live cells. We showed that BODIPY-labeled polyamides accumulate in acidic vesicles, mainly lysosomes, in the cytoplasm of HCT116 colon cancer cells and human rheumatoid synovial fibroblasts (RSF). Verapamil blocked vesicular accumulation and led to nuclear accumulation of the BODIPY-labeled polyamide in RSFs. We infer that the basic amine group commonly found at the end of synthetic polyamide chains is responsible for their accumulation in cytoplasmic vesicles in mammalian cells. Modifying the charge on a polyamide by replacing the BODIPY moiety with a fluorescein moiety on the amine tail allowed the polyamide to localize in the nucleus of the cell and bypass the cytoplasmic vesicles in HCT116 cells.