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This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

Summary: Background: Insulin resistance (IR) is an important risk factor for multiple chronic diseases, increasing mortality and reducing life expectancy. The associations between emerging surrogates for IR, triglyceride-glucose index (TyG) and TyG-related indicators, with all-cause mortality and life expectancy in middle-aged and older patients in primary care are unclear. Methods: This study originated from the Polish primary care cohort LIPIDOGRAM2015, including patients aged ≥45 years. Baseline fasting triglycerides and fasting glucose were used to derive TyG. Other TyG-related indicators included TyG-adjusted body mass index (TyG-BMI), TyG-adjusted waist circumference (TyG-WC), TyG-adjusted waist-to-hip, and TyG-adjusted waist-to-height. In this longitudinal analysis, we assessed associations between TyG-related indicators with total all-cause mortality, premature (age at death ≤75 years) all-cause mortality and years of life lost (YLL). Findings: We included 10,688 patients (mean age 61.8 ± 9.3 years; 63.5% female). Cumulative total and premature all-cause mortality were 7.2% and 4.6%, respectively, during 5.7 years (IQR 5.6–5.7) of follow-up. Lowest (Q1) and highest quartile (Q4) of TyG-BMI and TyG-WC were associated with total all-cause mortality (second quartile [Q2]: reference; TyG-BMI: Q1: aHR 1.33, 95% CI 1.07–1.65, Q4: aHR 1.28, 95% CI 1.03–1.58; TyG-WC: Q1: aHR 1.44, 95% CI 1.14–1.82, Q4: aHR 1.29, 95% CI 1.04–1.59), similar results for premature all-cause mortality. Within age 45–80 years, compared with Q2 and third quartile, YLL were 4.49 and 5.46 years for TyG-BMI Q1 and Q4, respectively, 3.24 and 5.31 years for TyG-WC Q1 and Q4, respectively. Interpretation: TyG-BMI and TyG-WC demonstrated a U-shaped association with total and premature all-cause mortality. Low and high levels of TyG-BMI and TyG-WC were associated with reduced life expectancy. Despite the relatively short follow-up period, significant associations were still observed, but longer follow-up studies are required to further explore these relationships. Funding: Polish Lipid Association, College of Family Physician in Poland, Valeant in Poland.

BACKGROUND: Many states in the United States have progressed towards legalization of marijuana including decriminalization, medicinal and/or recreational use. We studied the impact of legalization on cannabis-related emergency department visits in states with varying degrees of legalization. METHODS: Seventeen healthcare institutions in fifteen states (California, Colorado, Connecticut, Florida, Iowa, Kentucky, Maryland, Massachusetts, Missouri, New Hampshire, Oregon, South Carolina, Tennessee, Texas, Washington) participated. Cannabinoid immunoassay results and cannabis-related International Classification of Diseases (ninth and tenth versions) codes were obtained for emergency department visits over a 3- to 8-year period during various stages of legalization: no state laws, decriminalized, medical approval before dispensaries, medical dispensaries available, recreational approval before dispensaries and recreational dispensaries available. Trends and monthly rates of cannabinoid immunoassay and cannabis-related International Classification of Diseases code positivity were determined during these legalization periods. RESULTS: For most states, there was a significant increase in both cannabinoid immunoassay and International Classification of Diseases code positivity as legalization progressed; however, positivity rates differed. The availability of dispensaries may impact positivity in states with medical and/or recreational approval. In most states with no laws, there was a significant but smaller increase in cannabinoid immunoassay positivity rates. CONCLUSIONS: States may experience an increase in cannabis-related emergency department visits with progression toward marijuana legalization. The differences between states, including those in which no impact was seen, are likely multifactorial and include cultural norms, attitudes of local law enforcement, differing patient populations, legalization in surrounding states, availability of dispensaries, various ordering protocols in the emergency department, and the prevalence of non-regulated cannabis products.

ObjectivesThe objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines.Design and methodsA cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections.ResultsNAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (

ImportanceMost healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster.ObjectiveWe determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals.DesignA COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19.ResultsThere were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson.Conclusions and relevanceYounger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.

This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

ImportanceMost healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster.ObjectiveWe determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals.DesignA COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19.ResultsThere were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson.Conclusions and relevanceYounger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.

Beta-lactam antibiotics remain one of the most commonly prescribed drug classes, but they are limited by their propensity to cause hypersensitivity reactions (e.g., from allergy to anaphylaxis) as well as by the emergence of bacteria with a myriad of resistance mechanisms such as β-lactamases. While development efforts continue to focus on overcoming resistance, there are ongoing concerns regarding cross-contamination of β-lactams during manufacturing and compounding of these drugs. Additionally, there is a need to reduce levels of drugs such as β-lactam antibiotics in waste-water to mitigate the risk of environmental exposure. To help address future development of effective remediation chemistries and processes, it is desired to better understand the structural relationship among the most common β-lactams. This study includes the creation of a class-wide structural ordering of the entire β-lactam series, including both United States Food and Drug Association (US-FDA)-approved drugs and experimental therapies. The result is a structural relational map: the “Lactamome,” which positions each substance according to architecture and chemical end-group. We utilized a novel method to compare the structural relationships of β-lactam antibiotics among the radial cladogram and describe the positioning with respect to efficacy, resistance to hydrolysis, reported hypersensitivity, and Woodward height. The resulting classification scheme may help with the development of broad-spectrum treatments that reduce the risk of occupational exposure and negative environmental impacts, assist practitioners with avoiding adverse patient reactions, and help direct future drug research.

Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (

Palliative care is interdisciplinary care that addresses suffering and improves the quality of care for patients and families when patients are facing a life-threatening illness. Palliative care needs in the intensive care unit include communication regarding diagnosis and prognosis, goals-of-care conversations, multidimensional pain and symptom management, and end-of-life care that may include withdrawal of mechanical ventilation and life support. Registered nurses spend the greatest amount of time with patients and families who are facing death and serious illness, so nurses must be armed with adequate training, knowledge, and necessary tools to address patient and caregiver needs and deliver high-quality, patient-centered palliative care. Innovative approaches to integrating palliative care are important components of care for intensive care nurses. This article reviews 2 evidence-based practice projects, a serious illness support tool and the 3 Wishes Project, to add to the palliative care toolkit for registered nurses and other team members. [ABSTRACT FROM AUTHOR]

Intensive care unit–based palliative care has evolved over the past 30 years due to the efforts of clinicians, researchers, and advocates for patient-centered care. Although all critically ill patients inherently have palliative care needs, the path was not linear but rather filled with the challenges of blending the intensive care unit goals of aggressive treatment and cure with the palliative care goals of symptom management and quality of life. Today, palliative care is considered an essential component of high-quality critical care and a core competency of all critical care nurses, advanced practice nurses, and other intensive care unit clinicians. This article provides an overview of the current state of intensive care unit–based palliative care, examines how the barriers to such care have shifted, reviews primary and specialist palliative care, addresses the impact of COVID-19, and presents resources to help nurses and intensive care unit teams achieve optimal outcomes. [ABSTRACT FROM AUTHOR]

tRNAs are linked with their cognate amino acid by aminoacyl tRNA synthetases (ARS). Here, the authors report a developmental encephalopathy associated with biallelic VARS variants (valyl-tRNA synthetase) that lead to loss of function, as determined by several in vitro assays and a vars knockout zebrafish model.

Glaesserella parasuis (Gps) causes high economic losses in pig farms worldwide. So far no vaccine provides cross-protection for different serotypes, so antibiotic treatment is widely used to cope with this pathogen. In this study, routine diagnostic data from 2046 pigs with Gps related diseases sent for necropsy to a German laboratory in the time period 2006–2021 were analysed retrospectively. In the time period 2018–2021, the most frequent serotypes (ST) detected were ST4 (30%) and ST13 (22%). A comparison of the reference period 2006–2013 prior to obligatory routine recording of antimicrobial usage in livestock with the period 2014–2021 resulted in a statistically significant decrease of frequencies of resistant Gps isolates for ceftiofur, enrofloxacin, erythromycin, spectinomycin, tiamulin and tilmicosin. While in 2006–2013 all isolates were resistant for tetracyclin and cephalothin, frequencies of resistant isolates decreased in the second time period to 28% and 62%, respectively. Parallel to the reduction of antimicrobial usage, during recent years a reduction in resistant Gps isolates has been observed, so only a low risk of treatment failure exists. Most frequently, pigs positive for Gps were also positive for S.suis (25.4%), PRRSV-EU (25.1%) and influenza virus (23%). The viral pathogens may act as potential trigger factors.

The Caribbean Archipelago is a biodiversity hotspot that plays a key role in developing our understanding of how dispersal ability affects species formation. In island systems, species with intermediate dispersal abilities tend to exhibit greater diversity, as may be the case for many of the salticid lineages of the insular Caribbean. Here, we use molecular phylogenetic analyses to infer patterns of relationships and biogeographic history of the Caribbean endemic Antillattus clade (Antillattus, Truncattus, and Petemethis). We test if the timing of origin of the Antillatus clade in the Greater Antilles is congruent with GAARlandia and infer patterns of diversification within the Antillattus clade among Cuba, Hispaniola, and Puerto Rico. Specifically, we evaluate the relative roles of dispersal over land connections, and overwater dispersal events in diversification within the Greater Antilles. Time tree analysis and model-based inference of ancestral ranges estimated the ancestor of the Antillattus clade to be c. 25 Mya, and the best model suggests dispersal via GAARlandia from northern South America to Hispaniola. Hispaniola seems to be the nucleus from which ancestral populations dispersed into Cuba and Puerto Rico via land connections prior to the opening of the Mona Passage and the Windward Passage. Divergences between taxa of the Antillattus clade from Cuban, Hispaniolan, and Puerto Rican populations appear to have originated by vicariance, founder-events and within-island speciation, while multiple dispersal events (founder-events) between Cuba and Hispaniola during the Middle Miocene and the Late Miocene best explain diversity patterns in the genera Antillattus and Truncattus.

Background: Despite the increased awareness of social determinants of health (SDoH), integrating social needs screening into health care practice has not consistently occurred. Local Problem: No social needs screening using recommended standardized questions was available at an outpatient hemodialysis clinic. Methods: Plan-Do-Study-Act cycles, based on the Model for Improvement, were used to implement the Core 5 SDoH screening tool, a staff referral process, and an evaluation of the implementation process. Intervention: A standardized social needs screening tool and a staff referral process were implemented. An evaluation of the implementation process also occurred. Results: Of 73 patients screened, 21 reported 32 unmet social needs; all received referrals to community resources. Nurses demonstrated high acceptance and usability of the tool and the referral process. Conclusions: Implementing a standardized screening and referral process customized to clinical workflow enhanced the identification of social needs in patients undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

Linear section of grains in polyhedral material microstructure is a system of chords. The mean length of chords is the linear grain size of the microstructure. For the prior austenite grains of low alloy structural steels, the chord length is a random variable of gamma- or logarithmic-normal distribution. The statistical grain size estimation belongs to the quantitative metallographic problems. The so-called point estimation is a well known procedure. The interval estimation (grain size confidence interval) for the gamma distribution was given elsewhere, but for the logarithmic-normal distribution is the subject of the present contribution. The statistical analysis is analogous to the one for the gamma distribution.

The surface protein composition of extracellular vesicles (EVs) is related to the originating cell and may play a role in vesicle function. Knowledge of the protein content of individual EVs is still limited because of the technical challenges to analyse small vesicles. Here, we introduce a novel multiplex bead-based platform to investigate up to 39 different surface markers in one sample. The combination of capture antibody beads with fluorescently labelled detection antibodies allows the analysis of EVs that carry surface markers recognized by both antibodies. This new method enables an easy screening of surface markers on populations of EVs. By combining different capture and detection antibodies, additional information on relative expression levels and potential vesicle subpopulations is gained. We also established a protocol to visualize individual EVs by stimulated emission depletion (STED) microscopy. Thereby, markers on single EVs can be detected by fluorophore-conjugated antibodies. We used the multiplex platform and STED microscopy to show for the first time that NK cell–derived EVs and platelet-derived EVs are devoid of CD9 or CD81, respectively, and that EVs isolated from activated B cells comprise different EV subpopulations. We speculate that, according to our STED data, tetraspanins might not be homogenously distributed but may mostly appear as clusters on EV subpopulations. Finally, we demonstrate that EV mixtures can be separated by magnetic beads and analysed subsequently with the multiplex platform. Both the multiplex bead-based platform and STED microscopy revealed subpopulations of EVs that have been indistinguishable by most analysis tools used so far. We expect that an in-depth view on EV heterogeneity will contribute to our understanding of different EVs and functions.

Linear section of grains in polyhedral material microstructure is a system of chords on a test line. The mean chord length is the linear grain size of the material. In the prior austenite microstructure of low alloy structural steels, the chord length is a random variable which has the gamma distribution. The distribution parameters are closely related to the austenite linear grain size. Because the sequent chord lengths are statistically independent, the grain size interval estimation (confidence interval) may be performed by the chi-square distribution.

Objective. This study was performed to review the clinical utility of commercial laboratory Toxoplasmosis-specific IgM testing during pregnancy and outcomes of the gestation at our institution.

The production of over 800 1.3-GHz superconducting (SC) cavities for the European X-ray Free Electron Laser (EXFEL), the largest in the history of cavity fabrication, has now been successfully completed. In the past, manufacturing of SC resonators was only partly industrialized; the main challenge for the EXFEL production was transferring the high-performance surface treatment to industry. The production was shared by the two companies RI Research Instruments GmbH (RI) and Ettore Zanon S.p.A. (EZ) on the principle of “build to print”. DESY provided the high-purity niobium and NbTi for the resonators. Conformity with the European Pressure Equipment Directive (PED) was developed together with the contracted notified body TUEV NORD. New or upgraded infrastructure has been established at both companies. Series production and delivery of fully-equipped cavities ready for cold rf testing was started in December 2012, and finished in December 2015. More than half the cavities delivered to DESY as specified (referred to “as received”) fulfilled the EXFEL specification. Further improvement of low-performing cavities was achieved by supplementary surface treatment at DESY or at the companies. The final achieved average gradient exceeded the EXFEL specification by approximately 25%. In the following paper, experience with the 1.3-GHz cavity production for EXFEL is reported and the main lessons learned are discussed.

In the United States, more than 350 000 cardiac arrests occur annually. The survival rate after an out-of-hospital cardiac arrest remains low. The majority of patients who have return of spontaneous circulation will die of complications of hypoxic-ischemic brain injury. Targeted temperature management is the only recommended neuroprotective measure for those who do not regain consciousness after return of spontaneous circulation. Despite current practices, a review of the literature revealed that evidence on the ideal time to achieve target temperature after return of spontaneous circulation remains equivocal. A program evaluation of a targeted temperature management program at an academic center was performed; the focus was on timing components of targeted temperature management. The program evaluation revealed that nurse-driven, evidence-based protocols can lead to optimal patient outcomes in this low-frequency, high-impact therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Glucagon is a peptide hormone with many uses as a therapeutic agent, including the emergency treatment of hypoglycemia. Physical instability of glucagon in solution leads to problems with the manufacture, formulation, and delivery of this pharmaceutical product. Glucagon has been shown to aggregate and form fibrils and gels in vitro. Small oligomeric precursors serve to initiate and nucleate the aggregation process. In this study, these initial aggregates, or seed nuclei, are characterized in bulk solution using light scattering methods and field-flow fractionation. Results High molecular weight aggregates of glucagon were detected in otherwise monomeric solutions using light scattering techniques. These aggregates were detected upon initial mixing of glucagon powder in dilute HCl and NaOH. In the pharmaceutically relevant case of acidic glucagon, the removal of aggregates by filtration significantly slowed the aggregation process. Field-flow fractionation was used to separate aggregates from monomeric glucagon and determine relative mass. The molar mass of the large aggregates was shown to grow appreciably over time as the glucagon solutions gelled. Conclusion The results of this study indicate that initial glucagon solutions are predominantly monomeric, but contain small quantities of large aggregates. These results suggest that the initial aggregates are seed nuclei, or intermediates which catalyze the aggregation process, even at low concentrations.