Southern Region Produce Safety Alliance Grower Training: Using Pre- and Post-Training Knowledge Assessments to Understand Training Effectiveness.

The Produce Safety Alliance (PSA) grower training was introduced in 2016 as the standardized curriculum to meet the training requirements of the Food and Drug Administration's (FDA) Food Safety Modernization Act's (FSMA) Produce Safety Rule (PSR). The PSR states that at least one supervisor or responsible party from each farm must have successfully completed this food safety training or one equivalent to the standardized curriculum, as recognized by the FDA. This study evaluated the effectiveness of PSA trainings conducted between 2017 and 2019 in the Southern United States by the Southern Regional Center for Food Safety Training, Outreach, and Technical Assistance by analyzing pre- and posttest assessments. Effectiveness was based on a 25-question knowledge assessment administered to participants before (n = 2494) and after (n = 2460) each training. The knowledge assessment indicated the overall effectiveness of the training, with average scores increasing significantly from pretest (15.9/25, 63.4%) to posttest (20.3/25, 81.3%) (P < 0.001). The greatest knowledge gains were seen in the Postharvest Handling and Sanitation, How to Develop a Farm Food Safety Plan, and Agricultural Water modules. Notably, these modules had lower posttest scores compared to the other modules, indicating that the amount of knowledge gained did not necessarily correspond with a sufficient understanding of the material. To ensure that participants understand all aspects of the PSR and best practices to minimize food safety risks, additional or advanced trainings may be needed. Additionally, the current testing instrument (pre-/posttest) used for PSA grower training, while validated, may not be optimal, thus alternative methods to assess the training effectiveness are likely needed.

Viability and Proliferation Assessment of Gingival Fibroblasts Cultured on Silver Nanoparticle-Doped Ti-6Al-4V Surfaces.

PURPOSE: To investigate the biocompatibility of silver nanoparticle (AgNP)-doped Ti-6Al-4V surfaces by evaluating the viability and proliferation rate of human gingival fibroblasts (HGFs)-as the dominant cells of peri-implant soft tissues-seeded on the modified surfaces. MATERIALS AND METHODS: AgNPs (sizes 8 nm and 30 nm) were incorporated onto Ti-6Al-4V specimen surfaces via electrochemical deposition, using colloid silver dispersions with increasing AgNP concentrations of 100 ppm, 200 ppm, and 300 ppm. One control and six experimental groups were included in the study: (1) control (Ti-6Al-4V), (2) 8 nm/100 ppm, (3) 8 nm/200 ppm, (4) 8 nm/300 ppm, (5) 30 nm/100 ppm, (6) 30 nm/200 ppm, and (7) 30 nm/300 ppm. HGF cell primary cultures were isolated from periodontally healthy donor patients and cultured in direct contact with the group specimens for 24 and 72 hours. The cytotoxicity of AgNP-doped Ti-6Al-4V specimens toward HGF was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and BrdU (5-bromo-2'-deoxyuridine) assay tests. Calcein AM and ethidium homodimer (EthD-1) fluorescent stains were used to determine the live and dead cells. The morphology and attachment properties of the HGFs were determined via scanning electron microscopy (SEM). RESULTS: Energy dispersive x-ray (EDX) analysis confirmed the presence of AgNPs on the specimens. The MTT test revealed that AgNPs of both sizes and all concentrations presented a decreased cellular metabolic activity compared to the control discs. All concentrations of both sizes of AgNPs affected the cell proliferation rate compared to the control group, as revealed by the BrdU assay. Overall, cytotoxicity of the modified Ti-6Al-4V surfaces depended on cell exposure time. Observation via confocal microscopy confirmed the results of the MTT and BrdU assay tests. Specifically, most cells remained alive throughout the 72-hour culture period. SEM images revealed that adjacent cells form bonds with each other, creating confluent layers of conjugated cells. CONCLUSIONS: The findings of the present study indicate that Ti-6Al-4V surfaces modified with 8 nm and 30 nm AgNPs at concentrations of 100 ppm, 200 ppm, and 300 ppm do not produce any serious cytotoxicity toward HGFs. The initial arrest of the HGF proliferation rate recovered at 72 hours. These results on the antibacterial activity against common periodontal pathogens, in combination with the results found in a previous study by the same research group, suggest that AgNP-doped Ti-6Al-4V surfaces are potential candidates for use in implant abutments for preventing peri-implant diseases.

Randomized controlled multi-centre study comparing shorter dental implants (6 mm) to longer dental implants (11-15 mm) in combination with sinus floor elevation procedures: 10-year data.

AIM: To compare implant survival and complication rates between shorter and standard-length implants with sinus augmentation and restored with single crowns, at 10 years of loading. MATERIALS AND METHODS: One-hundred and one patients (137 implants) with a ridge height of 5-7 mm in the posterior maxilla were randomly assigned to two treatment modalities: shorter implants (6 mm) (group short [GS]) or standard-length implants (11-15 mm) with sinus grafting (group graft [GG]). Following the insertion of final restorations, patients were regularly recalled for up to 10 years. Assessed outcomes encompassed implant survival, marginal bone levels (MBLs), biological and technical parameters and patient-reported outcome measures (OHIP-49 = Oral Health Impact Profile). Non-parametric statistical analysis was used to analyse the data. RESULTS: For the 5- to 10-year follow-up period, 77 patients with 105 implants (GS: 36 patients/48 implants; GG: 41/57) were available for re-examination (drop-out rate 21%). Implant survival rates at the patient level were 96.0% (GS; 2 failures) and 100% (GG) (inter-group p = .24). Median MBLs amounted to 0.00 mm (min 0.00; max 3.25; GS) and 0.00 mm (min 0.00; max 4.55; GG) (inter-group p = .73). Technical complications predominantly occurred within the first 5 years (inter-group p > .05). Peri-implantitis rates were 4.2% (GS) and 13.3% (GG) (intergroup p = .37). Median OHIP-49 scores were 7.00 (0.00; 39.00; GS) and 9.00 (0.00; 196; GG) (inter-group p = .61) at 10 years. CONCLUSIONS: Based on similar 10-year implant survival rates, reduced patient morbidity and lower costs, the use of shorter dental implants might well serve as an alternative treatment concept to longer implants placed in conjunction with sinus grafting for patients with a limited ridge height in the posterior maxilla. Study register: https://clinicaltrials.gov/ct2/show/NCT01030523.

Edible nano-encapsulated cinnamon essential oil hybrid wax coatings for enhancing apple safety against food borne pathogens.

Post-harvest losses of fruits due to decay and concerns regarding microbial food safety are significant within the produce processing industry. Additionally, maintaining the quality of exported commodities to distant countries continues to pose a challenge. To address these issues, the application of bioactive compounds, such as essential oils, has gained recognition as a means to extend shelf life by acting as antimicrobials. Herein, we have undertaken an innovative approach by nano-encapsulating cinnamon-bark essential oil using whey protein concentrate and imbibing nano-encapsulates into food-grade wax commonly applied on produce surfaces. We have comprehensively examined the physical, chemical, and antimicrobial properties of this hybrid wax to evaluate its efficacy in combatting the various foodborne pathogens that frequently trouble producers and handlers in the post-harvest processing industry. The coatings as applied demonstrated a static contact angle of 85 ± 1.6°, and advancing and receding contact angles of 90 ± 1.1° and 53.0 ± 1.6°, respectively, resembling the wetting properties of natural waxes on apples. Nanoencapsulation significantly delayed the release of essential oil, increasing the half-life by 61 h compared to its unencapsulated counterparts. This delay correlated with statistically significant reductions (p = 0.05) in bacterial populations providing both immediate and delayed (up to 72 h) antibacterial effects as well as expanded fungal growth inhibition zones compared to existing wax technologies, demonstrating promising applicability for high-quality fruit storage and export. The utilization of this advanced produce wax coating technology offers considerable potential for bolstering food safety and providing enhanced protection against bacteria and fungi for produce commodities.

Estimation of Numbers of Testing Personnel and Test Volume in the Clinical Laboratory Improvement Amendments of 1988 Certificate of Accreditation and Certificate of Compliance Laboratories in the United States.

CONTEXT.­: Two major categories of laboratories performing nonwaived testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) are the Certificate of Accreditation (CoA) and Certificate of Compliance (CoC) laboratories. Accreditation organizations collect more detailed laboratory personnel information than the Centers for Medicare & Medicaid Services (CMS) Quality Improvement and Evaluation System (QIES). OBJECTIVE.­: To estimate total numbers of testing personnel and testing volumes in CoA and CoC laboratories, by laboratory type and state. DESIGN.­: We developed a statistical inference method by using the respective correlations between testing personnel counts and test volume by laboratory type. RESULTS.­: QIES reported 33 033 active CoA and CoC laboratories in July 2021. We estimated testing personnel to be 328 000 (95% CI, 309 000-348 000), which is supported by the count of 318 780 reported by the US Bureau of Labor Statistics. There were twice as many testing personnel in hospital laboratories as in independent laboratories (158 778 versus 74 904, P < .001). Independent laboratories had the highest test volume per person, which was twice as high as physician office laboratories (62 228 versus 30 102, P < .001). Hospital and independent laboratories comprised 34% of all CoA and CoC laboratories but performed the largest portion of testing (81%). Physician office laboratories, accounting for 44% of all CoA and CoC laboratories, performed a comparatively low proportion of total tests (9%). CONCLUSIONS.­: Numbers of testing personnel vary considerably by laboratory type and across states. These data can provide valuable insight when assessing laboratory workforce training needs and planning for public health emergencies.

Prenatal FGFR2 Signaling via PI3K/AKT Specifies the PDGFRA+ Myofibroblast.

It is well known that FGFR2 (fibroblast growth factor receptor 2) signaling is critical for proper lung development. Recent studies demonstrate that epithelial FGFR2 signaling during the saccular phase of lung development (sacculation) regulates alveolar type 1 (AT1) and AT2 cell differentiation. During sacculation, PDGFRA (platelet-derived growth factor receptor-α)-positive lung fibroblasts exist as three functional subtypes: contractile myofibroblasts, extracellular matrix-producing matrix fibroblasts, and lipofibroblasts. All three subtypes are required during alveolarization to establish a niche that supports AT2 epithelial cell self-renewal and AT1 epithelial cell differentiation. FGFR2 signaling directs myofibroblast differentiation in PDGFRA+ fibroblasts during alveolar reseptation after pneumonectomy. However, it remains unknown if FGFR2 signaling regulates PDGFRA+ myo-, matrix, or lipofibroblast differentiation during sacculation. In this study, FGFR2 signaling was inhibited by temporal expression of a secreted dominant-negative FGFR2b (dnFGFR2) by AT2 cells from embryonic day (E) 16.5 to E18.5. Fibroblast and epithelial differentiation were analyzed at E18.5 and postnatal days 7 and 21. At all time points, the number of myofibroblasts was reduced and the number of lipo-/matrix fibroblasts was increased. AT2 cells are increased and AT1 cells are reduced postnatally, but not at E18.5. Similarly, in organoids made with PDGFRA+ fibroblasts from dnFGFR2 lungs, increased AT2 cells and reduced AT1 cells were observed. In vitro treatment of primary wild-type E16.5 adherent saccular lung fibroblasts with recombinant dnFGFR2b/c resulted in reduced myofibroblast contraction. Treatment with the PI3K/AKT activator 740 Y-P rescued the lack of myofibroblast differentiation caused by dnFGFR2b/2c. Moreover, treatment with the PI3K/AKT activator 740 Y-P rescued myofibroblast differentiation in E18.5 fibroblasts isolated from dnFGFR2 lungs.

The role of the retinal vasculature in age-related macular degeneration: a spotlight on OCTA.

Age-related macular degeneration (AMD) remains a disease with high morbidity and an incompletely understood pathophysiological mechanism. The ocular blood supply has been implicated in the development of the disease process, of which most research has focused on the role of the choroid and choriocapillaris. Recently, interest has developed into the role of the retinal vasculature in AMD, particularly with the advent of optical coherence tomography angiography (OCTA), which enables non-invasive imaging of the eye's blood vessels. This review summarises the up-to-date body of work in this field including the proposed links between observed changes in the retinal vessels and the development of AMD and potential future directions for research in this area. The review highlights that the strongest evidence supports the observation that patients with early to intermediate AMD have reduced vessel density in the superficial vascular complex of the retina, but also emphasises the need for caution when interpreting such studies due to their variable methodologies and nomenclature.

A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma.

INTRODUCTION: This study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC). PATIENTS AND METHODS: Single institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed. RESULTS: Fifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%. CONCLUSION: The combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC. CLINICALTRIALS: GOV: NCT04868773.

Conversion of the anatomic crown of a natural tooth to an interim-retained restoration for enhanced esthetics and soft tissue stability in the maxillary esthetic zone: A clinical report.

Immediate non-functional loading of an implant in the anterior region is a documented treatment modality with high success rates. This therapeutic approach is frequently used to overcome esthetic and functional problems during the provisionalization period, but also because it provides better support of the peri-implant soft tissues. For that purpose, an implant-supported resin restoration, either traditionally or digitally made, is used. This clinical report describes the modification of patient's natural tooth, that was previously fractured, used as an implant-supported provisional restoration to obtain better esthetics and preservation of the soft tissues in their original, pre-extraction, position.

Knowledge, Attitude, Behavior Practices and Compliance of Workers Exposed to Respirable Dust in a Zambian Copper Mine.

Work in the copper mining industry is often associated with exposure to respirable dust and respirable crystalline silica. This exposure has the potential to cause silicosis, an incurable occupational respiratory lung disease. This study aimed at establishing the relationship between knowledge, attitudes, work behavioral practices and compliance with safety standards and workers' exposure to respirable dust. A cross-sectional descriptive survey was conducted on 528 mine workers. The Statistical Package for Social Sciences (SPSS) was used for the descriptives. Structural equation modeling (SEM) with latent variables and partial least squares (LVPLS) analysis were employed to determine the relationship among these variables. The results indicated that of the four hypotheses, two were supported, and two were rejected, showing that there is a significant relationship between exposure to respirable dust and work behavioral practices, as well as compliance with safety standards. Knowledge and attitudes toward respirable dust exposure did not significantly influence exposure. According to the results from the survey, positive work behavioral practices as well as compliance with safety standards were significantly associated with exposure to respirable dust. It is recommended that mines should focus on the miners' work behavioral practices and compliance with safety standards.

Affimer-mediated locking of p21-activated kinase 5 in an intermediate activation state results in kinase inhibition.

Kinases are important therapeutic targets, and their inhibitors are classified according to their mechanism of action, which range from blocking ATP binding to covalent inhibition. Here, a mechanism of inhibition is highlighted by capturing p21-activated kinase 5 (PAK5) in an intermediate state of activation using an Affimer reagent that binds in the P+1 pocket. PAK5 was identified from a non-hypothesis-driven high-content imaging RNAi screen in urothelial cancer cells. Silencing of PAK5 resulted in reduced cell number, G1/S arrest, and enlargement of cells, suggesting it to be important in urothelial cancer cell line survival and proliferation. Affimer reagents were isolated to identify mechanisms of inhibition. The Affimer PAK5-Af17 recapitulated the phenotype seen with siRNA. Co-crystallization revealed that PAK5-Af17 bound in the P+1 pocket of PAK5, locking the kinase into a partial activation state. This mechanism of inhibition indicates that another class of kinase inhibitors is possible.

Lethality Validation for Human Pathogenic Salmonella enterica on Chicken Feathers and Blood during Simulated Commercial Low-Temperature Dry Rendering.

Poultry rendering is the process of upcycling inedible poultry carcass materials into useful animal food/feed components as well as other valuable commercial products. Microbiological safety validation is nonetheless critical to ensuring the prevention of food safety hazard(s) transmission. This study determined the death kinetics of the thermotolerant Salmonella enterica serovar Senftenberg isolate 775W in chicken feathers and blood in low-temperature dry rendering (i.e., no direct contact with heating medium) to validate pathogen inactivation in commercial processing. Chicken feathers and blood were inoculated with Salmonella Senftenberg 775W and heated to 60, 70, or 80 °C for up to 60, 20, and 5 min, respectively. Three identically completed replicates (N = 3) for each product were conducted. Pathogen inactivation data were fitted to a non-linear model, providing for the detection and characterization of shoulder, log-linear death, and tailing components in death curves. The analysis showed a >7-log10 reduction in Salmonella was achieved across all processing temperatures, with t7D values (time for 7.0 log-cycle lethality) ranging from 21.68, 7.30, and 4.26 min for feathers and 18.38, 5.03, and 2.79 min in blood at 60, 70, and 80 °C, respectively. Study findings validate that low-temperature processing conditions can inactivate Salmonella in poultry-rendered offal.

Comparison of electronic versus mechanical torque-limiting devices for dental implants: An in vitro study.

PURPOSE: To determine the accuracy of new electronic torque-limiting devices (ET) when compared to new and used conventional-style beam-type (BT) mechanical torque-limiting devices and hand-piece style (HS) mechanical torque-limiting devices. The secondary purpose was to compare any difference in accuracy between new and used mechanical torque-limiting devices, and any difference in accuracy when used on a straight versus an angled screw channel abutment. MATERIALS AND METHODS: A total of five torque-limiting devices were used to obtain 2000 readings under standardized conditions. An implant analog was fastened into a digital torque meter, to which an abutment was connected. Pre-determined torque values of 15 Ncm and 35 Ncm were applied, and actual torque values were recorded. A straight and an angled abutment were used to record 1000 readings each using the five torque-limiting devices. An overall Kruskal-Wallis test was applied to compare the median deviation among devices followed by a pairwise comparison ( = 0.05). RESULTS: For a target torque value of 15 Ncm on a straight abutment, the electronic device (ET) was statistically more accurate than the beam type (BT) new (p < 0.001) and used (p < 0.048) devices but less accurate than the hand-piece style (HS) used device (p < 0.001). On an angled abutment for a target value of 15 Ncm, the electronic device (ET) was statistically more accurate than hand-piece style (HS) new and used devices (p < 0.001). For a target torque value of 35 Ncm on a straight abutment, the ET was statistically more accurate than the HS new device (p < 0.001) but less accurate than the BT new device (p < 0.001). On an angled abutment for a target value of 35 Ncm, the electronic device (ET) was statistically less accurate than the beam-type (BT) new device (p < 0.001), the beam-type (BT) used device (p = 0.001), and the hand-piece style (HS) used device (p < 0.001). The electronic device (ET) was the only device accurate within the ISO standard of accuracy of 6% for each of the target torque value/abutment design combinations. There was no statistically significant difference related to the type of abutment used (angled vs. straight). CONCLUSIONS: Electronic torque limiting devices (ET) are an acceptable method for delivering torque for implant restorations for straight and angled abutments at 15 Ncm and 35 Ncm torque values. Conventional style beam-type (BT) mechanical torque-limiting devices are a simple, predictable, validated, and inexpensive tool for delivering accurate torque at 15 Ncm and 35 Ncm torque values. The hand-piece style (HS) mechanical torque-limiting devices are predictable to deliver 15 Ncm torque values.

Phase IIa Clinical Biomarker Trial of Dietary Arginine Restriction and Aspirin in Colorectal Cancer Patients.

After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD (p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention (p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine (p < 0.13), spermine (p < 0.21), spermidine:spermine ratio (p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.

Immunotherapy with CD25/CD71-allodepleted T cells to improve T-cell reconstitution after matched unrelated donor hematopoietic stem cell transplant: a randomized trial.

BACKGROUND AIMS: Delayed immune reconstitution is a major challenge after matched unrelated donor (MUD) stem cell transplant (SCT). In this randomized phase 2 multi-center trial, Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant (NCT01827579), the authors tested whether allodepleted donor T cells (ADTs) can safely be used to improve immune reconstitution after alemtuzumab-based MUD SCT for hematological malignancies. METHODS: Patients received standard of care or up to three escalating doses of ADTs generated through CD25+/CD71+ immunomagnetic depletion. The primary endpoint of the study was circulating CD3+ T-cell count at 4 months post-SCT. Twenty-one patients were treated, 13 in the ADT arm and eight in the control arm. RESULTS: The authors observed a trend toward improved CD3+ T-cell count at 4 months in the ADT arm versus the control arm (230/µL versus 145/µL, P = 0.18), and three ADT patients achieved normal CD3+ T-cell count at 4 months (>700/µL). The rates of significant graft-versus-host disease (GVHD) were comparable in both cohorts, with grade ≥2 acute GVHD in seven of 13 and four of eight patients and chronic GVHD in three of 13 and three of eight patients in the ADT and control arms, respectively. CONCLUSIONS: These data suggest that adoptive transfer of ADTs is safe, but that in the MUD setting the benefit in terms of T-cell reconstitution is limited. This approach may be of more use in the context of more rigorous T-cell depletion.

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment.

BACKGROUND: Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival. METHODS: Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 µg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration. RESULTS: Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%. CONCLUSIONS: AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted. TRIAL REGISTRATION: NCT, NCT03400917 , Registered 10 January 2018.

Role of space station instruments for improving tropical carbon flux estimates using atmospheric data.

The tropics is the nexus for many of the remaining gaps in our knowledge of environmental science, including the carbon cycle and atmospheric chemistry, with dire consequences for our ability to describe the Earth system response to a warming world. Difficulties associated with accessibility, coordinated funding models and economic instabilities preclude the establishment of a dense pan-tropical ground-based atmospheric measurement network that would otherwise help to describe the evolving state of tropical ecosystems and the associated biosphere-atmosphere fluxes on decadal timescales. The growing number of relevant sensors aboard sun-synchronous polar orbiters provide invaluable information over the remote tropics, but a large fraction of the data collected along their orbits is from higher latitudes. The International Space Station (ISS), which is in a low-inclination, precessing orbit, has already demonstrated value as a proving ground for Earth observing atmospheric sensors and as a testbed for new technology. Because low-inclination orbits spend more time collecting data over the tropics, we argue that the ISS and its successors, offer key opportunities to host new Earth-observing atmospheric sensors that can lead to a step change in our understanding of tropical carbon fluxes.

Teaching pharmacy students a systematic approach to medication order verification.

BACKGROUND AND PURPOSE: Inpatient medication order verification is an important skill for pharmacy students to learn for patient safety. This article describes a systematic approach to order verification that enables students to apply didactic knowledge and determine the presence of drug therapy problems during verification decisions. EDUCATIONAL ACTIVITY AND SETTING: At two different colleges of pharmacy, an order verification module for second-year pharmacy students introduced a checklist for reviewing medication orders in a patient chart and identifying the presence of drug therapy problems. Students had to make a "verify or not" decision for each non-verified order and document their decision in both the chart and on a game-based learning platform. FINDINGS: Over four academic years, 756 students participated in the module. With the checklist approach to order verification, students were able to identify the drug therapy problems of "dose too high" and "no drug therapy problem present" but were challenged by "wrong drug," "dose too low/renal dosing," and "duplication of therapy." SUMMARY: The order verification checklist was a beneficial tool for teaching a systematic approach to inpatient medication order verification.

A digital approach to asthma self-management in adults: Protocol for a pragmatic randomized controlled trial.

Asthma self-management can improve symptom control, but adherence to established self-management behaviors is often poor. With adult asthma uncontrolled in over 60% of U.S. cases, there is a need for scalable, cost-effective tools to improve asthma outcomes. Here we describe a protocol for the Asthma Digital Study, a 24-month, decentralized, pragmatic, open-label, randomized controlled trial investigating the impact of a digital asthma self-management (DASM) program on asthma outcomes in adults. The program leverages consumer-grade devices with a smartphone app to provide "smart nudges," symptom logging, trigger tracking, and other features. Participants are recruited (target N = 900) from throughout the U.S., and randomized to a DASM or control arm (1:1). Co-primary outcomes at one year are a) asthma-associated costs for acute care and b) change from baseline in Asthma Control Test™ scores. Findings may inform decisions around adoption of digital tools for asthma self-management. Trial registration:clinicaltrials.gov identifier: NCT04609644. Registered: Oct 30, 2020.