Sodium status of collapsed marathon runners Kratz, Alexander; Siegel, Arthur J; Verbalis, Joseph G ...
Archives of pathology & laboratory medicine (1976)
129, Številka:
2
Journal Article
Recenzirano
Recommendations for prevention and treatment of medical emergencies in participants in marathon races center on maintenance of adequate hydration status and administration of fluids. Recently, new ...recommendations for fluid replacement for marathon runners were promulgated by medical and athletic societies. These new guidelines encourage runners to drink ad libitum between 400 and 800 mL/h as opposed to the previous "as much as possible" advice.
To assess the sodium and hydration (plasma osmolality) status of collapsed marathon runners after the promulgation of new hydration guidelines.
Plasma sodium and osmolality values of runners who presented to the medical tent at the finish line of the 2003 Boston Marathon were measured.
Using reference ranges derived from the general population, of 140 collapsed runners, 35 (25%) were hypernatremic (sodium, >146 mEq/L) and 6 (12%) were hyperosmolar (osmolality, >296 mOsm/kg H(2)O), whereas 9 (6%) were hyponatremic (sodium, <135 mEq/L) and 8 (16%) were hypo-osmolar (osmolality, <280 mOsm/kg H(2)O). Compared with a population of marathon runners who had experienced no medical difficulties, 9% of the runners were hypernatremic, 5% were hyponatremic, 8% were hypo-osmolar, and none were hyperosmolar.
Our findings indicate a significant incidence of hypernatremia with hyperosmolality and hyponatremia with hypo-osmolality among collapsed runners despite the new fluid intake recommendations, suggesting that either further educational measures are required or that the new guidelines are not entirely adequate to prevent abnormalities in fluid balance. Furthermore, the immediate medical management of hypernatremia and hyponatremia is different. Administration of fluids to severely hyponatremic patients may result in fatal cerebral edema. Our findings caution against institution of treatment until laboratory tests determine the patient's sodium status.
A vaccine against enterotoxigenic Escherichia coli (ETEC) is needed to prevent diarrheal illness among children in developing countries and at-risk travelers. Two live attenuated ETEC strains, PTL002 ...and PTL003, which express the ETEC colonization factor CFA/II, were evaluated for safety and immunogenicity. In a randomized, double-blind, placebo-controlled trial, 19 subjects ingested one dose, and 21 subjects ingested two doses (days 0 and 10) of PTL-002 or PTL-003 at 2 x 10⁹ CFU/dose. Anti-CFA/II mucosal immune responses were determined from the number of antibody-secreting cells (ASC) in blood measured by enzyme-linked immunospot assay, the antibody in lymphocyte supernatants (ALS) measured by enzyme-linked immunosorbent assay (ELISA), and fecal immunoglobulin A (IgA) levels determined by ELISA. Time-resolved fluorescence (TRF) ELISA was more sensitive than standard colorimetric ELISA for measuring serum antibody responses to CFA/II and its components, CS1 and CS3. Both constructs were well tolerated. Mild diarrhea occurred after 2 of 31 doses (6%) of PTL-003. PTL-003 produced more sustained intestinal colonization than PTL-002 and better IgA response rates: 90% versus 55% (P = 0.01) for anti-CFA/II IgA-ASCs, 55% versus 30% (P = 0.11) for serum anti-CS1 IgA by TRF, and 65% versus 25% (P = 0.03) for serum anti-CS3 IgA by TRF. Serum IgG response rates to CS1 or CS3 were 55% in PTL-003 recipients and 15% in PTL-002 recipients (P = 0.02). Two doses of either strain were not significantly more immunogenic than one. Based on its superior immunogenicity, which was comparable to that of a virulent ETEC strain and other ETEC vaccine candidates, PTL-003 will be developed further as a component of a live, oral attenuated ETEC vaccine.
Undoubtedly, the economic burden of cardiac care will continue to rise because of the rising costs of cardiac technological advances (3) and the increasing prevalence of cardiac disease (4). ...we ...can expect that public and private payers will increase their focus on both improving the quality and efficiency of cardiac care. There are essentially no randomized controlled trials demonstrating the effectiveness of P4P programs and very few reports in the literature that analyze the existing programs (5,11-14). Because of the lack of health services research and solid supporting evidence regarding P4P programs, the ACC and other organizations (15-18) have developed principles to guide their members and payers through the transition to novel payment mechanisms.
Purpose - This paper aims to unravel the complexities associated with knowledge sharing in large global organizations through a field study carried out in a large, multinational company (Du Pont), ...focusing on the critical issues, concrete practices, bottle-necks, and constraints in knowledge sharing. The tension between "local" production of much of the knowledge and its globalizing is specifically addressed.Design methodology approach - Qualitative analysis based on a detailed case study of the knowledge-sharing practices in two business units, two functional areas (R&D and engineering project management) in four countries.Findings - Focus on certain types of organizational knowledge to the exclusion of others can be counter-productive. Knowledge management (KM) systems need to be integrative and flexible enough to facilitate the dynamic interplay between different forms of knowledge across the space and time.Research limitations implications - The results of a case study are somewhat limited in terms of their generalizablity.Practical implications - The insights from the study offer useful guidelines for designing systems and processes for sharing and managing knowledge in large, diversified organizations.Originality value - Most field-based investigations into knowledge management tend to focus on specific KM projects. This is one of the few comprehensive studies that analyzed knowledge-sharing practices and constraints at both local and global level in large organizations. It elucidates the key facilitators and inhibitors of knowledge sharing in such organizations.
Background: Hyponatremia is a prevalent condition in patients hospitalized across a broad range of conditions, including heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic ...hormone (SIADH) secretion. Whether present on admission or developing during hospitalization, hyponatremia has been associated with increased mortality, longer hospital stays, and higher costs. Little is known, however, about its management and outcomes outside of clinical trial settings. Methods: The Hyponatremia Registry (HN Registry) is a prospective, observational, multi-center, multinational study of patients hospitalized with either hypervolemic hyponatremia (cirrhosis and heart failure) in the United States or euvolemic hyponatremia (SIADH) in both the United States and Europe. Study enrollment began in September 2010 at community, tertiary, and academic medical centers. Overall, the HN Registry is expected to enroll > 5,000 patients with hyponatremia, at > 280 sites. Data will be used to characterize demographic and clinical characteristics of patients hospitalized with hyponatremia, evaluate the comparative effectiveness of available treatment modalities, and document and compare length of hospital stay as a reflection of resource use associated with hospital management. Discussion: Despite better understanding of the clinical consequences, economic impact, and prognostic significance of euvolemic and hypervolemic hyponatremia, there remains a need to evaluate current "real-world" management. The HN Registry is designed to provide contemporary data on in-hospital evaluation, management, and length of stay in a large cohort of adult patients with hyponatremia. The HN Registry generated several design and analytical challenges that required unique approaches to facilitate collection of the most clinically relevant data. Keywords: hypervolemia, euvolemia, methodology, design, registry
The Reply Verbalis, Joseph G.; Goldsmith, Steven R.; Greenberg, Arthur ...
The American journal of medicine,
07/2014, Letnik:
127, Številka:
7
Journal Article
Abstract
Background
First-generation COVID-19 vaccines are matched to spike protein of the Wuhan-H1 (WT) strain. Convalescent and vaccinee samples show reduced neutralization of SARS-CoV-2 variants ...of concern (VOC). Next generation DNA vaccines could be matched to single variants or synthetically designed for broader coverage of multiple VOCs.
Methods
The synthetic consensus (SynCon®) sequence for INO-4802 SARS-CoV-2 spike with focused RBD changes and dual proline mutations was codon-optimized (Figure 1). Sequences for wild-type (pWT) and B.1.351 (pB.1.351) were similarly optimized. Immunogenicity was evaluated in BALB/c mice. Pre-clinical efficacy was assessed in the Syrian Hamster model.
Figure 1. Design Strategy for INO-4802
Results
INO-4802 induced potent neutralizing antibody responses against WT, B.1.1.7, P.1, and B.1.351 VOC in a murine model. pWT vaccinated animals showed a 3-fold reduction in mean neutralizing ID50 for the B.1.351 pseudotyped virus. INO-4802 immunized animals had significantly higher (p = 0.0408) neutralizing capacity (mean ID50 816.16). ID50 of pB.1.351 serum was reduced 7-fold for B.1.1.7 and significantly lower (p = 0.0068) than INO-4802 (317.44). INO-4802 neutralized WT (548.28) comparable to pWT. INO-4802 also neutralized P.1 (1026.6) (Figure 2). pWT, pB.1.351 or INO-4802 induced similar T-cell responses against all variants. INO-4802 skewed towards a TH1-response. All hamsters vaccinated with INO-4802 or pB.1.351 were protected from weight loss after B.1.351 live virus challenge. 4/6 pWT immunized hamsters were completely protected. pWT immunized hamsters neutralized WT (1090) but not B.1.351 (39.16). INO-4802 neutralized both WT (672.2) and B.1.351 (1121) (Figure 3). We observed higher increase of binding titers following heterologous boost with INO-4802 (3.6 – 4.4 log2-fold change) than homologous boost with pWT (2.0 – 2.4 log2 fold change) (Figure 4).
Figure 2. INO-4802 Induces Functional Humoral Immune Response Against SARS-CoV-2 Variants of Concern
Figure 3. INO-4802 Protects Hamsters Against Challenge With B.1.351 Live Virus
Figure 4. Heterologous Boost with INO-4802 Induces Humoral Immune Response Against SARS-CoV-2 Variants
Conclusion
Vaccines matching single VOCs, like pB.1.351 and pWT, elicit responses against the matched antigen but have reduced cross-reactivity. Presenting a pan-SARS-CoV-2 approach, INO-4802 may offer substantial advantages in terms of cross-strain protection, reduced susceptibility to escape mutants and non-restricted geographical use.
Disclosures
Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Charles C. Reed, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Richa Kalia, MS, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, I have stock options with Inovio Pharmaceuticals as an employee.) Jared Tur, PhD, Inovio (Employee) Blake Schouest, PhD, Inovio Pharmaceuticals (Employee) Dustin Elwood, PhD, Inovio Pharmaceuticals (Employee) Arthur Doan, n/a, Inovio (Employee) Patrick Pezzoli, BS, Inovio (Employee) Dinah Amante, BS, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) J Joseph Kim, PhD, Inovio (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Kate Broderick, PhD, Inovio (Employee).
The comparison of individual genome sequences is a key task for modern studies of population genetics, genotype-phenotype associations, and genome evolution. The problem is difficult in part because ...commonly-used DNA sequencing hardware produces reads that are orders of magnitude smaller than the size of a single human chromosome. The detection of large genomic mutations known as structural variants (SVs) from these short sequencing reads has emerged has a particularly challenging problem. Numerous methods targeting this problem have been proposed, but it is difficult to assess their performance on real data since the ground truth is typically unknown. Moreover, complex SVs that escape detection by conventional algorithms are known to exist. We propose here a solution to both the complex SV detection problem and the issue of evaluating accuracy on real data.
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