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1. The Available Criteria for Different Sepsis Scoring Systems in the Emergency Department—A Retrospective Assessment

Author

Ramdeen S, Ferrell B, Bonk C, Schubel L, Littlejohn R, Capan M, Arnold R, and Miller K

Subjects
sepsis, scoring systems, available criteria, emergency department, patient safety, quality improvement, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Sanjhai Ramdeen,1 Brandon Ferrell,1 Christopher Bonk,2 Laura Schubel,2 Robin Littlejohn,2 Muge Capan,3 Ryan Arnold,4 Kristen Miller1,2 1Georgetown University School of Medicine, Washington, DC, USA; 2National Center for Human Factors in Healthcare, MedStar Health Research Institute, Washington, DC, USA; 3Decision Sciences & MIS Department, LeBow College of Business, Drexel University, Philadelphia, PA, USA; 4Department of Emergency Medicine, Drexel University School of Medicine, Philadelphia, PA, USACorrespondence: Kristen MillerNational Center for Human Factors in Healthcare, MedStar Health Research Institute, 3007 Tilden Street NW, Suite 6N, Washington, DC, 20008, USATel +1 2022433873Fax +1 8553449800Email Kristen.E.Miller@medstar.netObjective: The goal of the study was to assess the criteria availability of eight sepsis scoring methods within 6 hours of triage in the emergency department (ED).Design: Retrospective data analysis study.Setting: ED of MedStar Washington Hospital Center (MWHC), a 912-bed urban, tertiary hospital.Patients: Adult (age ≥ 18 years) patients presenting to the MWHC ED between June 1, 2017 and May 31, 2018 and admitted with a diagnosis of severe sepsis with or without shock.Main Outcomes Measured: Availability of sepsis scoring criteria of eight different sepsis scoring methods at three time points— 0 Hours (T0), 3 Hours (T1) and 6 Hours (T2) after arrival to the ED.Results: A total of 50 charts were reviewed, which included 23 (46%) males and 27 (54%) females. Forty-eight patients (96%) were Black or African American. Glasgow Coma Scale was available for all 50 patients at T0. Vital signs, except for temperature, were readily available (> 90%) at T0. The majority of laboratory values relevant for sepsis scoring criteria were available (> 90%) at T1, with exception to bilirubin (66%) and creatinine (80%). NEWS, PRESEP and qSOFA had greater than 90% criteria availability at triage. SOFA and SIRS consistently had the least percent of available criteria at all time points in the ED.Conclusion: The availability of patient data at different time points in a patient’s ED visit suggests that different scoring methods could be utilized to assess for sepsis as more patient information becomes available.Keywords: sepsis, scoring systems, available criteria, emergency department, patient safety, quality improvement

Published
2021

2. Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals

Author

Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Kloeckner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, McDonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, Bryant, LM, Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Kloeckner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, McDonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, and Bryant, LM

Abstract

Bryant-Li-Bhoj syndrome (BLBS), which became OMIM-classified in 2022 (OMIM: 619720, 619721), is caused by germline variants in the two genes that encode histone H3.3 (H3-3A/H3F3A and H3-3B/H3F3B) [1-4]. This syndrome is characterized by developmental delay/intellectual disability, craniofacial anomalies, hyper/hypotonia, and abnormal neuroimaging [1, 5]. BLBS was initially categorized as a progressive neurodegenerative syndrome caused by de novo heterozygous variants in either H3-3A or H3-3B [1-4]. Here, we analyze the data of the 58 previously published individuals along 38 unpublished, unrelated individuals. In this larger cohort of 96 people, we identify causative missense, synonymous, and stop-loss variants. We also expand upon the phenotypic characterization by elaborating on the neurodevelopmental component of BLBS. Notably, phenotypic heterogeneity was present even amongst individuals harboring the same variant. To explore the complex phenotypic variation in this expanded cohort, the relationships between syndromic phenotypes with three variables of interest were interrogated: sex, gene containing the causative variant, and variant location in the H3.3 protein. While specific genotype-phenotype correlations have not been conclusively delineated, the results presented here suggest that the location of the variants within the H3.3 protein and the affected gene (H3-3A or H3-3B) contribute more to the severity of distinct phenotypes than sex. Since these variables do not account for all BLBS phenotypic variability, these findings suggest that additional factors may play a role in modifying the phenotypes of affected individuals. Histones are poised at the interface of genetics and epigenetics, highlighting the potential role for gene-environment interactions and the importance of future research.

Published
2024

3. Correction: Expanded phenotypic spectrum of neurodevelopmental and neurodegenerative disorder Bryant-Li-Bhoj syndrome with 38 additional individuals (vol 3, 2024, 59)

Author

Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Toutain, A, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Klockner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, Mcdonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, Bryant, LM, Layo-Carris, DE, Lubin, EE, Sangree, AK, Clark, KJ, Durham, EL, Gonzalez, EM, Smith, S, Angireddy, R, Wang, XM, Weiss, E, Toutain, A, Mendoza-Londono, R, Dupuis, L, Damseh, N, Velasco, D, Valenzuela, I, Codina-Sola, M, Ziats, C, Have, J, Clarkson, K, Steel, D, Kurian, M, Barwick, K, Carrasco, D, Dagli, AI, Nowaczyk, MJM, Hancarova, M, Bendova, S, Prchalova, D, Sedlacek, Z, Baxova, A, Nowak, CB, Douglas, J, Chung, WK, Longo, N, Platzer, K, Klockner, C, Averdunk, L, Wieczorek, D, Krey, I, Zweier, C, Reis, A, Balci, T, Simon, M, Kroes, HY, Wiesener, A, Vasileiou, G, Marinakis, NM, Veltra, D, Sofocleous, C, Kosma, K, Synodinos, JT, Voudris, KA, Vuillaume, M-L, Gueguen, P, Derive, N, Colin, E, Battault, C, Au, B, Delatycki, M, Wallis, M, Gallacher, L, Majdoub, F, Smal, N, Weckhuysen, S, Schoonjans, A-S, Kooy, RF, Meuwissen, M, Cocanougher, BT, Taylor, K, Pizoli, CE, Mcdonald, MT, James, P, Roeder, ER, Littlejohn, R, Borja, NA, Thorson, W, King, K, Stoeva, R, Suerink, M, Nibbeling, E, Baskin, S, Guyader, GLE, Kaplan, J, Muss, C, Carere, DA, Bhoj, EJK, and Bryant, LM

Published
2024

4. Multidimensional quantum normal forms, Moyal star product, and torus quantization

Author

Cargo, Matthew, Gracia-Saz, Alfonso, and Littlejohn, R G

Subjects
Mathematical Physics
Abstract

A normal form transformation is carried out on the operators of a complete set of commuting observables in a multidimensional, integrable quantum system, mapping them by unitary conjugation into functions of the harmonic oscillators in the various degrees of freedom. The transformation works at the level of the Weyl symbols of the operators, which are manipulated as formal power series in hbar by use of the Moyal star product. It is assumed that the Weyl symbol of one of the operators (the Hamiltonian) has a generic, stable fixed point in phase space. The normal form transformation takes place in a neighborhood of this fixed point. Once the normal form has been achieved, the Einstein-Brillouin-Keller or torus quantization rule follows easily, including higher order corrections in hbar. Crucial parts of the normal form transformation are not obvious generalizations of the one-dimensional case, nor is final quantization rule. The result raises some issues of differential geometry not found in the one-dimensional case., Comment: 34 pages, 2 figures

Published
2005

5. Moyal star product approach to the Bohr-Sommerfeld approximation

Author

Cargo, Matthew, Gracia-Saz, Alfonso, Littlejohn, R. G., Reinsch, M. W., and Rios, P. de M.

Subjects
Mathematical Physics, Mathematics - Symplectic Geometry
Abstract

The Bohr-Sommerfeld approximation to the eigenvalues of a one-dimensional quantum Hamiltonian is derived through order $\hbar^2$ (i.e., including the first correction term beyond the usual result) by means of the Moyal star product. The Hamiltonian need only have a Weyl transform (or symbol) that is a power series in $\hbar$, starting with $\hbar^0$, with a generic fixed point in phase space. The Hamiltonian is not restricted to the kinetic-plus-potential form. The method involves transforming the Hamiltonian to a normal form, in which it becomes a function of the harmonic oscillator Hamiltonian. Diagrammatic and other techniques with potential applications to other normal form problems are presented for manipulating higher order terms in the Moyal series., Comment: 27 pages, no figures

Published
2004
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18. The effects of deer antler velvet extract or powder supplementation on aerobic power, erythropoiesis, and muscular strength and endurance characteristics.

Author

Sleivert G, Burke V, Palmer C, Walmsley A, Gerrard D, Haines S, and Littlejohn R

Abstract

To determine the effects of deer antler velvet on maximal aerobic performance and the trainability of muscular strength and endurance, 38 active males were randomly assigned in a double-blind fashion to either deer antler velvet extract (n = 12), powder (n = 13), or placebo groups (n = 13). Subjects were tested prior to beginning supplementation and a 10-week strength program, and immediately post-training. All subjects were measured for circulating levels of testosterone, insulin-like growth factor, erythropoietin, red cell mass, plasma volume, and total blood volume. Additionally, muscular strength, endurance, and VO2max were determined. All groups improved 6 RM strength equivalently (41 +/- 26%, p < .001), but there was a greater increase in isokinetic knee extensor strength (30 +/- 21% vs. 13 +/- 15%, p = .04) and endurance (21 +/- 19% vs. 7 +/- 12%, p = .02) in the powder compared to placebo group. There were no endocrine, red cell mass or VO2max changes in any group. These findings do not support an erythropoetic or aerobic ergogenic effect of deer antler velvet. Further, the inconsistent findings regarding the effects of deer antler velvet powder supplementation on the development of strength suggests that further work is required to test the robustness of the observation that this supplement enhances the strength training response and to ensure this observation is not a type I error. [ABSTRACT FROM AUTHOR]

Published
2003
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20. DNM1 encephalopathy

Author

Von Spiczak, S, Helbig, KL, Shinde, DN, Huether, R, Pendziwiat, M, Lourenço, C, Nunes, ME, Sarco, DP, Kaplan, RA, Dlugos, DJ, Kirsch, H, Slavotinek, A, Cilio, MR, Cervenka, MC, Cohen, JS, McClellan, R, Fatemi, A, Yuen, A, Sagawa, Y, Littlejohn, R, McLean, SD, Hernandez-Hernandez, L, Maher, B, Møller, RS, Palmer, E, Lawson, JA, Campbell, CA, Joshi, CN, Kolbe, DL, Hollingsworth, G, Neubauer, BA, Muhle, H, Stephani, U, Scheffer, IE, Pena, SDJ, Sisodiya, SM, Helbig, I, Von Spiczak, S, Helbig, KL, Shinde, DN, Huether, R, Pendziwiat, M, Lourenço, C, Nunes, ME, Sarco, DP, Kaplan, RA, Dlugos, DJ, Kirsch, H, Slavotinek, A, Cilio, MR, Cervenka, MC, Cohen, JS, McClellan, R, Fatemi, A, Yuen, A, Sagawa, Y, Littlejohn, R, McLean, SD, Hernandez-Hernandez, L, Maher, B, Møller, RS, Palmer, E, Lawson, JA, Campbell, CA, Joshi, CN, Kolbe, DL, Hollingsworth, G, Neubauer, BA, Muhle, H, Stephani, U, Scheffer, IE, Pena, SDJ, Sisodiya, SM, and Helbig, I

Abstract

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. Methods: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. Results: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. Conclusions: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

Published
2017

21. DNM1 encephalopathy A new disease of vesicle fission

Author

von Spiczak, S, Helbig, KL, Shinde, DN, Huether, R, Pendziwiat, M, Lourenco, C, Nunes, ME, Sarco, DP, Kaplan, RA, Dlugos, DJ, Kirsch, H, Slavotinek, A, Cilio, MR, Cervenka, MC, Cohen, JS, McClellan, R, Fatemi, A, Yuen, A, Sagawa, Y, Littlejohn, R, McLean, SD, Hernandez-Hernandez, L, Maher, B, Moller, RS, Palmer, E, Lawson, JA, Campbell, CA, Joshi, CN, Kolbe, DL, Hollingsworth, G, Neubauer, BA, Muhle, H, Stephani, U, Scheffer, IE, Pena, SDJ, Sisodiya, SM, Helbig, I, von Spiczak, S, Helbig, KL, Shinde, DN, Huether, R, Pendziwiat, M, Lourenco, C, Nunes, ME, Sarco, DP, Kaplan, RA, Dlugos, DJ, Kirsch, H, Slavotinek, A, Cilio, MR, Cervenka, MC, Cohen, JS, McClellan, R, Fatemi, A, Yuen, A, Sagawa, Y, Littlejohn, R, McLean, SD, Hernandez-Hernandez, L, Maher, B, Moller, RS, Palmer, E, Lawson, JA, Campbell, CA, Joshi, CN, Kolbe, DL, Hollingsworth, G, Neubauer, BA, Muhle, H, Stephani, U, Scheffer, IE, Pena, SDJ, Sisodiya, SM, and Helbig, I

Abstract

OBJECTIVE: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling. METHODS: We reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function. RESULTS: We identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function. CONCLUSIONS: The phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention.

Published
2017

27. Divergent Requirements for Technical and Non-Technical Coursework in Undergraduate Engineering Programs.

Author

FORBES, M. H., BIELEFELDT, A. R., SULLIVAN, J. F., and LITTLEJOHN, R. L.

Subjects
ENGINEERING education, UNDERGRADUATES, ENGINEERS, HUMANITIES, SOCIAL sciences, SOCIAL history
Abstract

Engineers need considerable understanding of humanities and social science to serve effectively and responsibly as professionals. Undergraduate engineering education faces pressures to add technical and non-technical content and decrease total credit hours, educational costs, and time to degree. This study characterizes how discipline-based engineering programs in the United States distribute required coursework between technical and non-technical areas of study in comparison to math, chemistry, and physics programs; the results could signal consensus or disparity in educational philosophy between and among institutions or disciplines. The distribution of technical versus non-technical coursework was delineated for 103 US News & World Report top-ranked and ABET EAC-accredited undergraduate programs in chemical, civil, electrical, and mechanical engineering based on 2013 catalog requirements, as well as chemistry, math, and physics programs at the same institutions. Technical was defined as coursework in engineering, math or natural science; non-technical was coursework outside of those disciplines. Findings reveal a wide range of required technical and non-technical course loads for all disciplines. For engineering, technical requirements ranged from 62% to 86% (median 75%) of total degree; non-technical requirements ranged from 12% to 35% (median 20%). The math, chemistry, and physics degrees were more balanced between technical and non-technical requirements. Differences in requirements suggest that consensus does not exist amongst engineering educators from this sampling of programs regarding the appropriate allocation of technical versus non-technical coursework for an undergraduate engineering education, and there are substantially divergent interpretations of what constitutes adequate "general education" for an engineer. Additionally, students who desire more well-rounded education might select non-engineering STEM majors. [ABSTRACT FROM AUTHOR]

Published
2017

37. Wave-packet evolution and quantization

Author

Littlejohn, R. G

Subjects
Physics (General)
Abstract

A general relationship is established between wave-packet evolution and quantization in classically integrable systems. Because of wave-packet spreading, one cannot simply take the Fourier transform of the time evolution of a wave-packet. Instead, one must propagate the wave-packet using the actions as Hamiltonians. The energy eigenvalues which result are the Einstein-Brillouin-Keller values, and new forms for the eigenfunctions appear. These are free of caustic singularities, and represent averages of wave packets over the invariant torus.

Published
1986
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