Interplay of management and environmental drivers shifts size structure of reef fish communities.

Countries are expanding marine protected area (MPA) networks to mitigate fisheries declines and support marine biodiversity. However, MPA impact evaluations typically assess total fish biomass. Here, we examine how fish biomass disaggregated by adult and juvenile life stages responds to environmental drivers, including sea surface temperature (SST) anomalies and human footprint, and multiple management types at 139 reef sites in the Mesoamerican Reef (MAR) region. We found that total fish biomass generally appears stable across the region from 2006 to 2018, with limited rebuilding of fish stocks in MPAs. However, the metric of total fish biomass masked changes in fish community structure, with lower adult than juvenile fish biomass at northern sites, and adult:juvenile ratios closer to 1:1 at southern sites. These shifts were associated with different responses of juvenile and adult fish to environmental drivers and management. Juvenile fish biomass increased at sites with high larval connectivity and coral cover, whereas adult fish biomass decreased at sites with greater human footprint and SST anomalies. Adult fish biomass decreased primarily in Honduran general use zones, which suggests insufficient protection for adult fish in the southern MAR. There was a north-south gradient in management and environmental drivers, with lower coverage of fully protected areas and higher SST anomalies and coastal development in the south that together may undermine the maintenance of adult fish biomass in the southern MAR. Accounting for the interplay between environmental drivers and management in the design of MPAs is critical for increasing fish biomass across life history stages.

Los países están ampliando las redes de áreas marinas protegidas (AMP) para mitigar la disminución de las pesquerías y apoyar la biodiversidad marina. Sin embargo, las evaluaciones de impacto de las AMP típicamente estudian la biomasa total de peces. Aquí, examinamos cómo la biomasa de peces desagregada por etapas de vida adultas y juveniles responde a factores ambientales como anomalías de la temperatura superficial del mar (SST) e impacto humano, y múltiples tipos de manejo en 139 sitios de arrecifes en el sistema arrecifal mesoamericano (SAM). Encontramos que la biomasa total de peces en general parece estable en toda la región entre 2006 y 2018, con una recuperación limitada de las poblaciones de peces en las AMP. Sin embargo, la métrica de biomasa total de peces enmascaró los cambios en la estructura de la comunidad de peces, con una biomasa de peces adultos más baja que juveniles en los sitios del norte, y proporciones adulto:juvenil más cercana a 1:1 en los sitios del sur. Estos cambios fueron asociados con diferentes respuestas de peces juveniles y adultos a variables ambientales y de manejo. La biomasa de peces juveniles aumentó en sitios con alta conectividad larvaria y cobertura coralina, mientras que la biomasa de peces adultos disminuyó en sitios con mayor impacto humano y anomalías en la SST. La biomasa de peces adultos disminuyó principalmente en las zonas de uso general (GUZ) hondureñas, lo cual sugiere una protección insuficiente para peces adultos en el sur del SAM. Hubo un gradiente norte­sur en el manejo y los factores ambientales, con menor cobertura de áreas totalmente protegidas y mayores anomalías de SST y desarrollo costero en el sur. En conjunto esto puede degradar el mantenimiento de la biomasa de peces adultos en el sur del SAM. La interacción entre factores ambientales y el manejo en el diseño de las AMP es fundamental para aumentar la biomasa de peces en todas las etapas del ciclo de vida.

Methicillin-Sensitive Staphylococcus aureus Co-infection in Adolescent Patients With Delta-Variant SARS-CoV-2 Acute Respiratory Failure.

We report a series of five pediatric patients admitted with acute respiratory failure due to delta-variant SARS-CoV-2, found to have a methicillin-sensitive Staphylococcus aureus (MSSA) co-infection. All five patients required escalation of their respiratory support within 24 hours of discovering the MSSA infections. Four out of the five patients received immune-modulating therapies. Four patients required extracorporeal membrane oxygenation support. One patient died, and the other four survived until hospital discharge. Clinicians should consider secondary bacterial infections in patients with COVID-19 treated with immune modulators. MSSA co-infection can lead to increased morbidity and mortality in patients with COVID-19.

Effects of management objectives and rules on marine conservation outcomes.

Understanding the relative effectiveness and enabling conditions of different area-based management tools is essential for supporting efforts that achieve positive biodiversity outcomes as area-based conservation coverage increases to meet newly set international targets. We used data from a coastal social-ecological monitoring program in 6 Indo-Pacific countries to analyze whether social, ecological, and economic objectives and specific management rules (temporal closures, fishing gear-specific, species-specific restrictions) were associated with coral reef fish biomass above sustainable yield levels across different types of area-based management tools (i.e., comparing those designated as marine protected areas [MPAs] with other types of area-based management). All categories of objectives, multiple combinations of rules, and all types of area-based management had some sites that were able to sustain high levels of reef fish biomass-a key measure for coral reef functioning-compared with reference sites with no area-based management. Yet, the same management types also had sites with low biomass. As governments advance their commitments to the Kunming-Montreal Global Biodiversity Framework and the target to conserve 30% of the planet's land and oceans by 2030, we found that although different types of management can be effective, most of the managed areas in our study regions did not meet criteria for effectiveness. These findings underscore the importance of strong management and governance of managed areas and the need to measure the ecological impact of area-based management rather than counting areas because of their designation.

Efectos de las reglas y objetivos de manejo sobre los resultados de conservación marina Resumen Es esencial entender la efectividad relativa y las condiciones habilitantes de las diferentes herramientas de manejo basadas en el área para respaldar los esfuerzos que brindan resultados positivos para la biodiversidad conforme aumenta la cobertura de la conservación basada en el área para alcanzar los objetivos internacionales recién establecidos. Usamos los datos de un programa de monitoreo socioeconómico costero en seis países del Indo-Pacífico para analizar si los objetivos sociales, ecológicos y económicos y las reglas específicas de manejo (cierres temporales, restricciones de equipo de pesca, vedas de especies) se asociaban con la biomasa de los peces de arrecife de coral por encima de los niveles de producción sustentable en diferentes tipos de herramientas de manejo basadas en el área (es decir, comparar aquellas designadas como áreas marinas protegidas[AMP] con otros tipos de manejo basado en el área). Todas las categorías de objetivos, las múltiples combinaciones de reglas y todos los tipos de manejo basado en el área tuvieron algunos sitios capaces de mantener los niveles altos de biomasa de peces de arrecife-una medida importante para el funcionamiento de los arrecifes-en comparación con los sitios de referencia sin manejo basado en el área. Sin embargo, los mismos tipos de manejo también tuvieron sitios con baja biomasa. Conforme los gobiernos avanzan en sus compromisos con el Marco Global de Biodiversidad de Kunming-Montreal y hacia el objetivo de conservar el 30% del suelo y los océanos del planeta para el 2030, descubrimos que, aunque diferentes tipos de manejo pueden ser efectivos, la mayoría de las áreas manejadas en nuestras regiones de estudio no cumplieron con los criterios de efectividad. Este descubrimiento enfatiza la importancia de una gestión y un gobierno sólidos de las áreas manejadas y la necesidad de medir el impacto ecológico del manejo basado en el área en lugar de contar las áreas por su designación.

Qualitative interviews to understand methods and systems used to collect ethnicity information in health administrative data sources in England.

Background: This article is one of a series aiming to inform analytical methods to improve comparability of estimates of ethnic health disparities based on different sources. This article explores the quality of ethnicity data and identifies potential sources of bias when ethnicity information is collected in three key NHS data sources. Future research can build on these findings to explore analytical methods to mitigate biases. Methods: Thematic analysis of semi-structured qualitative interviews to explore potential sources of error and bias in the process of collecting ethnicity information across three NHS data sources: General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR), Hospital Episode Statistics (HES) and Improving Access to Psychological Therapies (IAPT). The study included feedback from 22 experts working on different aspects of health admin data collection for England (including staff from NHS Digital, IT system suppliers and relevant healthcare service providers). Results: Potential sources of error and bias were identified across data collection, data processing and quality assurance processes. Similar issues were identified for all three sources. Our analysis revealed three main themes which can result in bias and inaccuracies in ethnicity data recorded: data infrastructure challenges, human challenges, and institutional challenges. Conclusions: Findings highlighted that analysts using health admin data should be aware of the main sources of potential error and bias in health admin data, and be mindful that the main sources of error identified are more likely to affect the ethnicity data for ethnic minority groups. Where possible, analysts should describe and seek to account for this bias in their research.

Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner.

Introduction: Soluble antigens complexed with immunoglobulin G (IgG) antibodies can induce robust adaptive immune responses in vitro and in animal models of disease. Factor VIII immune complexes (FVIII-ICs) have been detected in individuals with hemophilia A and severe von Willebrand disease following FVIII infusions. Yet, it is unclear if and how FVIII-ICs affect antibody development over time. Methods: In this study, we analyzed internalization of FVIII complexed with epitope-mapped FVIII-specific IgG monoclonal antibodies (MAbs) by murine bone marrow-derived dendritic cells (BMDCs) in vitro and antibody development in hemophilia A (FVIII-/-) mice injected with FVIII-IC over time. Results: FVIII complexed with 2-116 (A1 domain MAb), 2-113 (A3 domain MAb), and I55 (C2 domain MAb) significantly increased FVIII uptake by BMDC but only FVIII/2-116 enhanced antibody titers in FVIII-/- mice compared to FVIII alone. FVIII/4A4 (A2 domain MAb) showed similar FVIII uptake by BMDC to that of isolated FVIII yet significantly increased antibody titers when injected in FVIII-/- mice. Enhanced antibody responses observed with FVIII/2-116 and FVIII/4A4 complexes in vivo were abrogated in the absence of the FVIII carrier protein von Willebrand factor. Conclusion: These findings suggest that a subset of FVIII-IC modulates the humoral response to FVIII in an epitope-dependent manner, which may provide insight into the antibody response observed in some patients with hemophilia A.

Integrating larval connectivity into the marine conservation decision-making process across spatial scales.

Larval dispersal connectivity is typically integrated into spatial conservation decisions at regional or national scales, but implementing agencies struggle with translating these methods to local scales. We used larval dispersal connectivity at regional (hundreds of kilometers) and local (tens of kilometers) scales to aid in design of networks of no-take reserves in Southeast Sulawesi, Indonesia. We used Marxan with Connectivity informed by biophysical larval dispersal models and remotely sensed coral reef habitat data to design marine reserve networks for 4 commercially important reef species across the region. We complemented regional spatial prioritization with decision trees that combined network-based connectivity metrics and habitat quality to design reserve boundaries locally. Decision trees were used in consensus-based workshops with stakeholders to qualitatively assess site desirability, and Marxan was used to identify areas for subsequent network expansion. Priority areas for protection and expected benefits differed among species, with little overlap in reserve network solutions. Because reef quality varied considerably across reefs, we suggest reef degradation must inform the interpretation of larval dispersal patterns and the conservation benefits achievable from protecting reefs. Our methods can be readily applied by conservation practitioners, in this region and elsewhere, to integrate connectivity data across multiple spatial scales.

Integración de la conectividad larval al proceso de toma de decisiones en la conservación marina en escalas espaciales Resumen Comúnmente se integra la conectividad de la dispersión larval a las decisiones de conservación espacial a escalas regionales o nacionales, pero las agencias de implementación luchan con la transferencia de estos métodos a las escalas locales. Usamos la conectividad de la dispersión larval a escalas regionales (cientos de kilómetros) y locales (decenas de kilómetros) para ayudar en el diseño de redes de reservas con protección total en Sulawesi Sudoriental, Indonesia. Usamos Marxan con la conectividad guiada por los modelos biofísicos de dispersión larval y detectamos a distancia los datos de hábitat de los arrecifes de coral para diseñar redes de reservas marinas para cuatro especies de importancia comercial en la región. Complementamos la priorización espacial regional con árboles de decisión que combinaron medidas de conectividad basadas en las redes y la calidad del hábitat para diseñar localmente los límites de la reserva. Usamos los árboles de decisión con los actores en talleres basados en el consenso para evaluar cualitativamente la conveniencia del sitio. También usamos Marxan para identificar áreas para la expansión subsecuente de la red. Las áreas prioritarias para la protección y los beneficios esperados difirieron entre especies, con un traslape reducido en las soluciones de la red de reservas. Ya que la calidad del arrecife varió considerablemente entre los arrecifes, sugerimos que la degradación de estos debe orientar la interpretación de los patrones de dispersión larval y los beneficios de conservación alcanzables con la protección de los arrecifes. Los practicantes de la conservación pueden aplicar nuestros métodos inmediatamente, en esta región o en cualquier otra, para integrar los datos de conectividad en varias escalas espaciales.

Comparing spatial conservation prioritization methods with site- versus spatial dependency-based connectivity.

Larval dispersal is an important component of marine reserve networks. Two conceptually different approaches to incorporate dispersal connectivity into spatial planning of these networks exist, and it is an open question as to when either is most appropriate. Candidate reserve sites can be selected individually based on local properties of connectivity or on a spatial dependency-based approach of selecting clusters of strongly connected habitat patches. The first acts on individual sites, whereas the second acts on linked pairs of sites. We used a combination of larval dispersal simulations representing different seascapes and case studies of biophysical larval dispersal models in the Coral Triangle region and the province of Southeast Sulawesi, Indonesia, to compare the performance of these 2 methods in the spatial planning software Marxan. We explored the reserve design performance implications of different dispersal distances and patterns based on the equilibrium settlement of larvae in protected and unprotected areas. We further assessed different assumptions about metapopulation contributions from unprotected areas, including the case of 100% depletion and more moderate scenarios. The spatial dependency method was suitable when dispersal was limited, a high proportion of the area of interest was substantially degraded, or the target amount of habitat protected was low. Conversely, when subpopulations were well connected, the 100% depletion was relaxed, or more habitat was protected, protecting individual sites with high scores in metrics of connectivity was a better strategy. Spatial dependency methods generally produced more spatially clustered solutions with more benefits inside than outside reserves compared with site-based methods. Therefore, spatial dependency methods potentially provide better results for ecological persistence objectives over enhancing fisheries objectives, and vice versa. Different spatial prioritization methods of using connectivity are appropriate for different contexts, depending on dispersal characteristics, unprotected area contributions, habitat protection targets, and specific management objectives. Comparación entre los métodos de priorización de la conservación espacial con sitio y la conectividad espacial basada en la dependencia.

La dispersión larval es un componente importante de las redes de reservas marinas. Existen dos estrategias conceptualmente distintas para incorporar la conectividad de la dispersión en la planeación espacial de estas redes y es una pregunta abierta cuándo alguna de las dos es la más apropiada. Los sitios candidatos a reserva pueden ser seleccionados individualmente con base en las propiedades locales de la conectividad o en la estrategia espacial basada en la dependencia que consiste en seleccionar grupos de fragmentos de hábitat con un vínculo fuerte. La primera estrategia actúa sobre sitios individuales, mientras que la segunda actúa sobre pares de sitios vinculados. Usamos una combinación de simulaciones de dispersión larval que representaban a diferentes paisajes marinos y estudios de caso de modelos biofísicos de dispersión larval en la región del Triángulo de Coral y en la provincia de Sulawesi Sudoriental, Indonesia, para comparar el desempeño de estos dos métodos en el software de planeación espacial Marxan. Exploramos las implicaciones del desempeño del diseño de la reserva de diferentes distancias y patrones de dispersión basados en el establecimiento del equilibrio de larvas en las áreas protegidas y sin protección. Además, analizamos las suposiciones sobre las contribuciones metapoblacionales de las áreas sin protección, incluyendo el caso de la reducción al 100% y escenarios más moderados. El método de la dependencia espacial fue adecuado cuando la dispersión estuvo limitada, una proporción elevada del área de interés estaba sustancialmente degradada o era baja la cantidad meta de hábitat protegido. Al contrario, cuando las subpoblaciones estaban bien conectadas, la reducción al 100% estuvo relajada, o si una mayor parte del hábitat estaba protegido, la protección de los sitios individuales con altos puntajes en las medidas de conectividad fue una mejor estrategia. Los métodos de dependencia espacial generalmente produjeron soluciones con una agrupación más espacial y con más beneficios dentro que fuera de las reservas en comparación con los métodos basados sitios. Por lo tanto, los métodos de dependencia espacial tienen el potencial de proporcionar mejores resultados para los objetivos de persistencia ecológica por encima de los objetivos de mejora de las pesquerías, y viceversa. Los diferentes métodos de priorización espacial que usan la conectividad son apropiados para contextos diferentes, dependiendo de las características de dispersión, las contribuciones del área sin protección, las metas de protección del hábitat y los objetivos específicos del manejo.

Factors Associated with Information Breach in Healthcare Facilities: A Systematic Literature Review.

This systematic review aimed to identify the factors associated with information breaches in healthcare settings. We searched electronic databases, including PubMed, Embase, Scopus, and Wiley, for all publications until March 6, 2022 (no start date restriction) and outlined the eligibility criteria framework using Population, Concept, and Context (PCC). Our search strategies yielded 2,156 results, with nine studies included in the final review. We grouped the factors attributed to data breaches into four categories: organizational, information technology (IT), professionals/employees, and clients/patients. Hospital type, hospital size (more beds), higher operationalexpenses and revenue, higher admissions and discharges, and higher Electronic Medical Record (EMR) use, being at earlier phases of EMR adoption, were associated with higher information breaches. Professional factors such as the type of personnel involved and the hospital area can potentially impact the breaches' frequency and magnitude. Patients' sociodemographic, clinical, and behavioral characteristics, such as gender and educational attainment, appear to influence the perceived breach of confidentiality in healthcare settings. Identifying different factors contributing to health information breaches is crucial to protecting healthcare organizations and patients from the devastating consequences of data breaches.

Engineering a Therapeutic Protein to Enhance the Study of Anti-Drug Immunity.

The development of anti-drug antibodies represents a significant barrier to the utilization of protein-based therapies for a wide variety of diseases. While the rate of antibody formation can vary depending on the therapeutic employed and the target patient population receiving the drug, the antigen-specific immune response underlying the development of anti-drug antibodies often remains difficult to define. This is especially true for patients with hemophilia A who, following exposure, develop antibodies against the coagulation factor, factor VIII (FVIII). Models capable of studying this response in an antigen-specific manner have been lacking. To overcome this challenge, we engineered FVIII to contain a peptide (323-339) from the model antigen ovalbumin (OVA), a very common tool used to study antigen-specific immunity. FVIII with an OVA peptide (FVIII-OVA) retained clotting activity and possessed the ability to activate CD4 T cells specific to OVA323-339 in vitro. When compared to FVIII alone, FVIII-OVA also exhibited a similar level of immunogenicity, suggesting that the presence of OVA323-339 does not substantially alter the anti-FVIII immune response. Intriguingly, while little CD4 T cell response could be observed following exposure to FVIII-OVA alone, inclusion of anti-FVIII antibodies, recently shown to favorably modulate anti-FVIII immune responses, significantly enhanced CD4 T cell activation following FVIII-OVA exposure. These results demonstrate that model antigens can be incorporated into a therapeutic protein to study antigen-specific responses and more specifically that the CD4 T cell response to FVIII-OVA can be augmented by pre-existing anti-FVIII antibodies.

Neutralizing Antibodies Against Factor VIII Can Occur Through a Non-Germinal Center Pathway.

Humoral immunity to factor VIII (FVIII) represents a significant challenge for the treatment of patients with hemophilia A. Current paradigms indicate that neutralizing antibodies against FVIII (inhibitors) occur through a classical CD4 T cell, germinal center (GC) dependent process. However, clinical observations suggest that the nature of the immune response to FVIII may differ between patients. While some patients produce persistent low or high inhibitor titers, others generate a transient response. Moreover, FVIII reactive memory B cells are only detectable in some patients with sustained inhibitor titers. The determinants regulating the type of immune response a patient develops, let alone how the immune response differs in these patients remains incompletely understood. One hypothesis is that polymorphisms within immunoregulatory genes alter the underlying immune response to FVIII, and thereby the inhibitor response. Consistent with this, studies report that inhibitor titers to FVIII differ in animals with the same F8 pathogenic variant but completely distinct backgrounds; though, how these genetic disparities affect the immune response to FVIII remains to be investigated. Given this, we sought to mechanistically dissect how genetics impact the underlying immune response to FVIII. In particular, as the risk of producing inhibitors is weakly associated with differences in HLA, we hypothesized that genetic factors other than HLA influence the immune response to FVIII and downstream inhibitor formation. Our data demonstrate that FVIII deficient mice encoding the same MHC and F8 variant produce disparate inhibitor titers, and that the type of inhibitor response formed associates with the ability to generate GCs. Interestingly, the formation of antibodies through a GC or non-GC pathway does not appear to be due to differences in CD4 T cell immunity, as the CD4 T cell response to an immunodominant epitope in FVIII was similar in these mice. These results indicate that genetics can impact the process by which inhibitors develop and may in part explain the apparent propensity of patients to form distinct inhibitor responses. Moreover, these data highlight an underappreciated immunological pathway of humoral immunity to FVIII and lay the groundwork for identification of biomarkers for the development of approaches to tolerize against FVIII.

Participation, not penalties: Community involvement and equitable governance contribute to more effective multiuse protected areas.

Accelerating ecosystem degradation has spurred proposals to vastly expand the extent of protected areas (PAs), potentially affecting the livelihoods and well-being of indigenous peoples and local communities (IPLCs) worldwide. The benefits of multiuse PAs that elevate the role of IPLCs in management have long been recognized. However, quantitative examinations of how resource governance and the distribution of management rights affect conservation outcomes are vital for long-term sustainability. Here, we use a long-term, quasi-experimental monitoring dataset from four Indonesian marine PAs that demonstrates that multiuse PAs can increase fish biomass, but incorporating multiple governance principles into management regimes and enforcing rules equitably are critical to achieve ecological benefits. Furthermore, we show that PAs predicated primarily on enforcing penalties can be less effective than those where IPLCs have the capacity to engage in management. Our results suggest that well-governed multiuse PAs can achieve conservation objectives without undermining the rights of IPLCs.

Tranexamic acid use in the setting of ACE inhibitor induced angioedema.

Tranexamic acid (TXA) is an antifibrinolytic agent which reduces bradykinin production through its blockade of the conversion of plasminogen to plasmin and subsequently pre-kallikrein to kallikrein. It has been utilized in angiotensin converting enzyme (ACE) inhibitor-induced angioedema (ACEi-AE) in small case reports and series however overall data is limited. This report describes a patient who historically received TXA for ACEi-AE and represented with ACEi-AE after an accidental exposure and was successfully treated with TXA again. This case suggests TXA may be a safe and effective treatment option for ACEi-AE.

Twenty years of change in benthic communities across the Belizean Barrier Reef.

Disease, storms, ocean warming, and pollution have caused the mass mortality of reef-building corals across the Caribbean over the last four decades. Subsequently, stony corals have been replaced by macroalgae, bacterial mats, and invertebrates including soft corals and sponges, causing changes to the functioning of Caribbean reef ecosystems. Here we describe changes in the absolute cover of benthic reef taxa, including corals, gorgonians, sponges, and algae, at 15 fore-reef sites (12-15m depth) across the Belizean Barrier Reef (BBR) from 1997 to 2016. We also tested whether Marine Protected Areas (MPAs), in which fishing was prohibited but likely still occurred, mitigated these changes. Additionally, we determined whether ocean-temperature anomalies (measured via satellite) or local human impacts (estimated using the Human Influence Index, HII) were related to changes in benthic community structure. We observed a reduction in the cover of reef-building corals, including the long-lived, massive corals Orbicella spp. (from 13 to 2%), and an increase in fleshy and corticated macroalgae across most sites. These and other changes to the benthic communities were unaffected by local protection. The covers of hard-coral taxa, including Acropora spp., Montastraea cavernosa, Orbicella spp., and Porites spp., were negatively related to the frequency of ocean-temperature anomalies. Only gorgonian cover was related, negatively, to our metric of the magnitude of local impacts (HII). Our results suggest that benthic communities along the BBR have experienced disturbances that are beyond the capacity of the current management structure to mitigate. We recommend that managers devote greater resources and capacity to enforcing and expanding existing marine protected areas and to mitigating local stressors, and most importantly, that government, industry, and the public act immediately to reduce global carbon emissions.

Hypokalemia Measurement and Management in Patients With Status Asthmaticus on Continuous Albuterol.

OBJECTIVE: Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia. METHODS: This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol. RESULTS: Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2-3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times. CONCLUSIONS: The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks.

Removal of single-site N-linked glycans on factor VIII alters binding of domain-specific monoclonal antibodies.

BACKGROUND: A portion of individuals with hemophilia A develop neutralizing antibodies called inhibitors to glycoprotein factor VIII (FVIII). There are multiple risk factors that contribute to the risk of inhibitor formation. However, knowledge of the role of FVIII asparagine (N)-linked glycosylation in FVIII immunity is limited. OBJECTIVE: To evaluate the effect of site-specific N-linked glycan removal on FVIII biochemical properties, endocytosis by murine bone marrow-derived dendritic cells (BMDCs), and antibody responses. METHODS: Four recombinant B domain-deleted (BDD) FVIII variants with single-site amino acid substitutions to remove N-linked glycans were produced for experimental assays. RESULTS: BDD FVIII-N41G, FVIII-N239A, FVIII-N1810A, and FVIII-N2118A with confirmed removal of N-linked glycans and similar glycosylation profiles to BDD FVIII were produced. There were no differences in thrombin activation or von Willebrand factor binding of FVIII variants compared with BDD FVIII; however, reduced FVIII expression, activity, and specific activity was observed with all variants. BDD FVIII-N41G and FVIII-N1810A had reduced uptake by BMDCs, but there were no differences in antibody development in immunized hemophilia A mice compared with BDD FVIII. Half of a repertoire of 12 domain-specific FVIII MAbs had significantly reduced binding to ≥1 FVIII variant with a 50% decrease in A1 domain MAb 2-116 binding to FVIII-N239A. CONCLUSIONS: Modifications of FVIII N-linked glycans reduced FVIII endocytosis by BMDCs and binding of domain-specific FVIII MAbs, but did not alter de novo antibody production in hemophilia A mice, suggesting that N-glycans do not significantly contribute to inhibitor formation.

The Human Lumbar Spine During High-Rate Under Seat Loading: A Combined Metric Injury Criteria.

Modern changes in warfare have shown an increased incidence of lumbar spine injuries caused by underbody blast events. The susceptibility of the lumbar spine during these scenarios could be exacerbated by coupled moments that act with the rapid compressive force depending on the occupant's seated posture. In this study, a combined loading lumbar spine vertebral body fracture injury criteria (Lic) across a range of postures was established from 75 tests performed on instrumented cadaveric lumbar spine specimens. The spines were predominantly exposed to axial compressive forces from an upward vertical thrust with 64 of the tests resulting in at least one vertebral body fracture and 11 in no vertebral body injury. The proposed Lic utilizes a recommended metric (κ), based on prismatic beam failure theory, resulting from the combination of the T12-L1 resultant sagittal force and the decorrelated bending moment with optimized critical values of Fr,crit = 5824 N and My,crit = 1155 Nm. The 50% risk of lumbar spine injury corresponded to a combined metric of 1, with the risk decreasing with the combined metric value. At 50% injury risk the Normalized Confidence Interval Size improved from 0.24 of a force-based injury reference curve to 0.17 for the combined loading metric.