Montmorillonites saturated with small quaternary alkylammonium ions such as tetramethyl-ammonium (TMA) or trimethylphenylammonium (TMPA) are excellent sorbents for aromatic pollutants. In some cases, water inhibits arene sorption, but the inhibition mechanism is not understood completely. The objectives of this study were to determine whether arenes interact with adsorbed TMA and TMPA ions and/or with siloxane surfaces, and how water affects these interactions. We reacted benzene and ethylbenzene vapors with normal- and reduced-charge TMA- and TMPA-montmorillonite films at several relative humidities, and obtained infrared spectra of the resulting sorbate-clay complexes. Arene sorption caused the methyl asymmetric deformation vibrations adsorbed TMA and TMPA to shift to lower wave-number, whereas water sorption caused shifts to higher wavenumber. In the absence of water, benzene and ethylbenzene adsorbed on the siloxane surface as well as interacted directly with TMA and TMPA ions. The proportion of TMA and TMPA ions that interacted with benzene and ethylbenzene was greater for reduced-charge than normal-charge montmorillonite. Comparison of the HOH deformation and cation methyl asymmetric deformation vibrations indicated that both benzene and ethylbenzene inhibited water sorption substantially, and that water more readily displaced benzene and ethylbenzene from TMA and TMPA ions than from siloxane surfaces. Water inhibited arene sorption mainly by hydrating exchangeable cations, thereby obscuring siloxane surfaces adjacent to adsorbed TMA and TMPA ions and decreasing the average pore dimensions. These results indicate that in the presence of bulk water, arene adsorption likely occurs primarily on the siloxane surface.

Water inhibits sorption of uncharged organic compounds on montmorillonites saturated with small alkylammonium cations such as tetramethylammonium (TMA) and trimethylphenylammonium (TMPA). As a first step toward understanding the mechanism by which water inhibits arene sorption on TMA- and TMPA-montmorillonites, infrared spectroscopy and water sorption isotherm experiments were conducted to determine whether water preferentially hydrates adsorbed TMA and TMPA cations rather than the siloxane surface. Infrared spectra of normal-charge and reduced-charge TMA- and TMPA-montmorillonites were obtained at partial water vapor pressures from 0.075 to 0.92 to determine if water vapor hydrates the adsorbed cations. Water adsorbed at partial pressures from 0 to about 0.2 caused the wave-number position of the HOH deformation vibration of adsorbed water to shift 4 to 10 cm-1 to higher wavenumber and the methyl deformation vibrations of adsorbed TMA and TMPA cations to shift 1 to 2 cm-1 to higher wavenumber, providing evidence that water interacts directly with adsorbed TMA and TMPA ions. There were no shifts in the ring stretching or C-H out-of-plane vibrations of TMPA, which indicates that water interacts with the methyl groups of TMPA, not with TMPA's aromatic ring. Water vapor sorption isotherms showed that normal-charge montmorillonites adsorb more water than do reduced-charge montmorillonites, consistent with the higher concentration of adsorbed cations on normal-charge clay. More water was adsorbed by TMA-montmorillonite than by TMPA-montmorillonite, consistent with the higher hydration energy of TMA. Thus, both the infrared and sorption isotherm results show that water preferentially hydrates adsorbed TMA and TMPA, not the siloxane surface of montmorillonite.

The orientation of TMPA cations on montmorillonite affects the adsorbate-accessible siloxane surface area and determines whether the TMPA phenyl ring can interact with other aromatic adsorbates by π-π interactions. The purpose of this study was to determine the orientation of TMPA ions in the interlayer of normal-charge and reduced-charge Wyoming montmorillonite. The orientation of TMPA's phenyl group was investigated using infrared dichroism of selected aromatic ring vibrations. X-ray diffraction (XRD) and MacEwan Fourier transforms were used to determine interlayer spacings and to ascertain whether reduced-charge Wyoming montmorillonite is a randomly interstratified mixture of layers with two different d-spacings. For normal-charge montmorillonite, the infrared results showed that the C-N bond axis is neither perpendicular nor parallel to the surface, yet X-ray data suggested that the TMPA phenyl ring is perpendicular or nearly perpendicular to the siloxane surface. In this orientation, the average adsorbate-accessible space between adjacent TMPA ions is 24 Å2, or about 1/3 of the total surface. When the phenyl ring of TMPA is perpendicular to the clay surface, aromatic compounds should be able to interact with TMPA's aromatic ring by π-π interactions, while polar compounds such as water can interact with positively charged nitrogen atom. The reduced-charge montmorillonite used in this study is a randomly interstratified mixture of about 25% collapsed layers with no adsorbed cations and 75% expanded layers that are propped open by TMPA's methyl groups, not by the aromatic ring. The adsorbate-accessible surface area on expanded layers of reduced-charge montmorillonite is 1.5 to 2 times that on normal-charge TMPA-clay, depending on the orientation of TMPA's aromatic ring.

State Medical Boards (SMBs) can take severe disciplinary actions (e.g., license revocation or suspension) against physicians who commit egregious wrongdoing in order to protect the public. However, there is noteworthy variability in the extent to which SMBs impose severe disciplinary action. In this manuscript, we present and synthesize a subset of 11 recommendations based on findings from our team’s larger consensus-building project that identified a list of 56 policies and legal provisions SMBs can use to better protect patients from egregious wrongdoing by physicians.

Over the past 2 decades, several categorizations have been proposed for the abnormalities of the aortic root. These schemes have mostly been devoid of input from specialists of congenital cardiac disease. The aim of this review is to provide a classification, from the perspective of these specialists, based on an understanding of normal and abnormal morphogenesis and anatomy, with emphasis placed on the features of clinical and surgical relevance. We contend that the description of the congenitally malformed aortic root is simplified when approached in a fashion that recognizes the normal root to be made up of 3 leaflets, supported by their own sinuses, with the sinuses themselves separated by the interleaflet triangles. The malformed root, usually found in the setting of 3 sinuses, can also be found with 2 sinuses, and very rarely with 4 sinuses. This permits description of trisinuate, bisinuate, and quadrisinuate variants, respectively. This feature then provides the basis for classification of the anatomical and functional number of leaflets present. By offering standardized terms and definitions, we submit that our classification will be suitable for those working in all cardiac specialties, whether pediatric or adult. It is of equal value in the settings of acquired or congenital cardiac disease. Our recommendations will serve to amend and/or add to the existing International Paediatric and Congenital Cardiac Code, along with the Eleventh iteration of the International Classification of Diseases provided by the World Health Organization.

We honour a great man and a true giant. Lodewyk H.S. van Mierop (March 31, 1927 – October 17, 2021), known as Bob, was not only a Paediatric Cardiologist but also a dedicated Scientist. He made many significant and ground-breaking contributions to the fields of cardiac anatomy and embryology. He was devoted as a teacher, spending many hours with medical students, Residents, and Fellows, all of whom appreciated his regularly scheduled educational sessions. Those of us who were fortunate to know and spend time with him will always remember his great mind, his willingness to share his knowledge, and his ability to encourage spirited and fruitful discussions. His life was most productive, and he will long be remembered by many through his awesome and exemplary scientific contributions.

His legacy continues to influence the current and future generations of surgeons and all providers of paediatric and congenital cardiac care through the invaluable archive he established at University of Florida in Gainesville: The University of Florida van Mierop Heart Archive. Undoubtedly, with these extraordinary contributions to the fields of cardiac anatomy and embryology, which were way ahead of his time, Professor van Mierop was a true giant in Paediatric Cardiology. The invaluable archive he established at University of Florida in Gainesville, The University of Florida van Mierop Heart Archive, has been instrumental in teaching medical students, Residents, Medical Fellows, and Surgical Fellows. Only a handful of similar archives exist across the globe, and these archives are the true legacy of giants such as Dr. van Mierop. We have an important obligation to leave no stone unturned to continue to preserve these archives for the future generations of surgeons, physicians, all providers of paediatric and congenital cardiac care, and, most importantly, our patients.

In the December 2021 issue of Cardiology in the Young, Hubrechts and colleagues, from Brussels and Leuven in Belgium, describe their experience in which the pulmonary veins were normally connected to the morphologically left atrium. By virtue of the presence of a shelf dividing the morphologically left atrium, however, the venous return was to the morphologically right atrium, with no evidence of formation of the superior interatrial fold, meaning that there was no obstruction of flow into the systemic venous circulation. The question posed by the Belgian authors is whether the shelf dividing the morphologically left atrium is a deviated primary atrial septum, as the arrangement has previously been interpreted. As they discuss, it is currently impossible to arbitrate this conundrum. In our commentary, we discuss the background to the dilemma. We point out that, as yet, it is not possible to code accurately this congenital cardiac malformation within The International Paediatric and Congenital Cardiac Code (IPCCC), nor within the newly produced 11th Revision of the International Classification of Diseases (ICD-11).

OBJECTIVES/GOALS: Evaluate the migration and immune suppressive functions of CCR2+/CX3CR1+ myeloid-derived suppressor cells (MDSCs). Integrate experimental data and biologically relevant mathematical models of infiltrating MDSCs in the context of glioblastoma (GBM). METHODS/STUDY POPULATION: CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from CCR2(+/RFP)/CX3CR1(+/GFP) glioma-bearing mice to evaluate their immune-suppressive phenotype and ability to migrate to CCL2 and CCL7. Fluorescent imaging and quantification were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and MDSC densities. A system of ordinary differential equations was constructed to represent the temporal dynamics of glioma cells, T cells, and MDSCs within the tumor microenvironment. The Approximate Bayesian Computation method was used to determine probability distributions of important parameters, such as the suppression rate of T cells by MDSCs. RESULTS/ANTICIPATED RESULTS: CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor-bearing mice suppress CD8+ T cell proliferation and IFNγ production. CCR2+/CX3CR1+ cells migrate to recombinant and KR158B glioma sourced CCL2 and CCL7. Parameter values determined by the Approximate Bayesian Computation method agreed with parameter values from experimental data. This result further validated the structure and results of the mathematical model when performing computer simulations; thus, we can predict CCR2+/CX3CR1+ M-MDSC infiltration over time. DISCUSSION/SIGNIFICANCE: The immune-suppressive microenvironment in GBM contributes to poor outcomes despite standard of care. This study integrates biological and mathematical models to better understand infiltrating immune-suppressive cells, namely CCR2+/CX3CR1+ M-MDSCs. Future directions include modeling immunotherapies.

Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.

We identified quality indicators (QIs) for care during transitions of older persons (≥ 65 years of age). Through systematic literature review, we catalogued QIs related to older persons’ transitions in care among continuing care settings and between continuing care and acute care settings and back. Through two Delphi survey rounds, experts ranked relevance, feasibility, and scientific soundness of QIs. A steering committee reviewed QIs for their feasible capture in Canadian administrative databases. Our search yielded 326 QIs from 53 sources. A final set of 38 feasible indicators to measure in current practice was included. The highest proportions of indicators were for the emergency department (47%) and the Institute of Medicine (IOM) quality domain of effectiveness (39.5%). Most feasible indicators were outcome indicators. Our work highlights a lack of standardized transition QI development in practice, and the limitations of current free-text documentation systems in capturing relevant and consistent data.

ABSTRACT IMPACT: Predicting therapeutic responses in GBM. OBJECTIVES/GOALS: The goal of this team approach is to integrate mathematical models of glioblastoma (GBM) infiltrating myeloid cells that contribute to the immunosuppressive phenotype in glioma with experimental data to predict therapeutic responses to combined chemokine receptor and immune checkpoint blockade. METHODS/STUDY POPULATION: Orthotopic murine KR158-luc gliomas were established in fluorescent reporter CCR2WT/RFP CX3CR1WT/GFP mice. Subsequently, an anti-CD31 injection was administered to label the vasculature. Fluorescent imaging and quantification of anti-CD3 stained sections were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and myeloid cell densities. In parallel, a system of ordinary differential equations was formulated based on biological assumptions to evaluate the change over time of tumor cells, T cells, and infiltrating myeloid cells. The model was then refined and validated by experimental results. RESULTS/ANTICIPATED RESULTS: Fluorescent imaging and quantification revealed a correlation between tumor size and abundance of (CX3CR1+, CCR2-) and (CX3CR1+, CCR2+) myeloid cell populations in the tumor microenvironment. The density of these cell populations and vasculature remained constant as the tumors increased in size. Computer simulations of the mathematical model will predict tumor, myeloid, and T cell dynamics. These simulations will be particularly useful to uncover information regarding myeloid cell dynamics, such as cell entry time into the tumor microenvironment. Parameter sensitivity analysis of the model will inform us of the biological processes driving these tumor-immune cell dynamics. DISCUSSION/SIGNIFICANCE OF FINDINGS: GBM is a challenge as current intervention are ineffective. This study improves the understanding of glioma infiltrating myeloid cells and their impact on tumor progression. The data will serve as a basis for quantitatively predicting therapeutic responses of a novel combination treatment.

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.