An efficient algorithm for accelerating the convergence of oscillatory series, useful for computing the polylogarithm and Hurwitz zeta functions

This paper sketches a technique for improving the rate of convergence of a general oscillatory sequence, and then applies this series acceleration algorithm to the polylogarithm and the Hurwitz zeta function. As such, it may be taken as an extension of the techniques given by Borwein's "An efficient algorithm for computing the Riemann zeta function", to more general series. The algorithm provides a rapid means of evaluating Li_s(z) for general values of complex s and the region of complex z values given by |z^2/(z-1)|<4. Alternatively, the Hurwitz zeta can be very rapidly evaluated by means of an Euler-Maclaurin series. The polylogarithm and the Hurwitz zeta are related, in that two evaluations of the one can be used to obtain a value of the other; thus, either algorithm can be used to evaluate either function. The Euler-Maclaurin series is a clear performance winner for the Hurwitz zeta, while the Borwein algorithm is superior for evaluating the polylogarithm in the kidney-shaped region. Both algorithms are superior to the simple Taylor's series or direct summation. The primary, concrete result of this paper is an algorithm allows the exploration of the Hurwitz zeta in the critical strip, where fast algorithms are otherwise unavailable. A discussion of the monodromy group of the polylogarithm is included.Comment: 37 pages, 6 graphs, 14 full-color phase plots. v3: Added discussion of a fast Hurwitz algorithm; expanded development of the monodromy v4:Correction and clarifiction of monodrom

Quantitative biology: where modern biology meets physical sciences

Quantitative methods and approaches have been playing an increasingly important role in cell biology in recent years. They involve making accurate measurements to test a predefined hypothesis in order to compare experimental data with predictions generated by theoretical models, an approach that has benefited physicists for decades. Building quantitative models in experimental biology not only has led to discoveries of counterintuitive phenomena but has also opened up novel research directions. To make the biological sciences more quantitative, we believe a two-pronged approach needs to be taken. First, graduate training needs to be revamped to ensure biology students are adequately trained in physical and mathematical sciences and vice versa. Second, students of both the biological and the physical sciences need to be provided adequate opportunities for hands-on engagement with the methods and approaches necessary to be able to work at the intersection of the biological and physical sciences. We present the annual Physiology Course organized at the Marine Biological Laboratory (Woods Hole, MA) as a case study for a hands-on training program that gives young scientists the opportunity not only to acquire the tools of quantitative biology but also to develop the necessary thought processes that will enable them to bridge the gap between these disciplines

Profiling of external metabolites during production of hantavirus nucleocapsid protein with recombinant Saccharomyces cerevisiae

Recombinant strains of Saccharomyces cerevisiae, producing hantavirus Puumala nucleocapsid protein for diagnostics and as a candidate vaccine were analyzed for uptake and excretion of intermediary metabolites during process optimization studies of fed-batch bioreactor cultures. Concentrations of glucose, maltose, galactose, pyruvate, acetaldehyde, ethanol, acetate, succinate and formaldehyde (used as a selection agent) were measured in the culture medium in order to find a metabolite pattern, indicative for the physiological state of the producer culture. When the inducer galactose was employed as a growth substrate, the metabolite profile of recombinant yeast cells was different from those of the non-recombinant original strain which excreted considerable amounts of metabolites with this substrate. In contrast, galactose-induced heterologous gene expression was indicated by the absence of excreted intermediary metabolites, except succinate. A model strain expressing a GFP fusion of hantavirus nucleocapsid protein differed in the excretion of metabolites from strains without GFP. In addition, the influence of alkali ions, employed for pH control is also demonstrated

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. EXPOSURE: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). MAIN OUTCOMES AND MEASURES: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. RESULTS: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P \u3c .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P \u3c .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P \u3c .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. CONCLUSIONS AND RELEVANCE: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Abatacept pharmacokinetics and exposure response in patients hospitalized with COVID-19: A secondary analysis of the ACTIV-1 IM randomized clinical trial

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024. EXPOSURE: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg). MAIN OUTCOMES AND MEASURES: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity. RESULTS: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P \u3c .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P \u3c .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P \u3c .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure. CONCLUSIONS AND RELEVANCE: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

An evaluation of family physicians' educational needs and experiences in health promotion and disease prevention in Poland and Lithuania - a qualitative study

Reikšminiai žodžiai: Ligų prevencija; Sveikatos stiprinimas; Šeimos gydytojai; Šeimos gydytojų rengimas; Šeimos gydytojų švietimo poreikiai; Disease prevention; Family physicians; Family physicians educational needs; Health promotion; Training of family physician

Comparison of clinical knowledge management capabilities of commercially-available and leading internally-developed electronic health records

<p>Abstract</p> <p>Background</p> <p>We have carried out an extensive qualitative research program focused on the barriers and facilitators to successful adoption and use of various features of advanced, state-of-the-art electronic health records (EHRs) within large, academic, teaching facilities with long-standing EHR research and development programs. We have recently begun investigating smaller, community hospitals and out-patient clinics that rely on commercially-available EHRs. We sought to assess whether the current generation of commercially-available EHRs are capable of providing the clinical knowledge management features, functions, tools, and techniques required to deliver and maintain the clinical decision support (CDS) interventions required to support the recently defined "meaningful use" criteria.</p> <p>Methods</p> <p>We developed and fielded a 17-question survey to representatives from nine commercially available EHR vendors and four leading internally developed EHRs. The first part of the survey asked basic questions about the vendor's EHR. The second part asked specifically about the CDS-related system tools and capabilities that each vendor provides. The final section asked about clinical content.</p> <p>Results</p> <p>All of the vendors and institutions have multiple modules capable of providing clinical decision support interventions to clinicians. The majority of the systems were capable of performing almost all of the key knowledge management functions we identified.</p> <p>Conclusion</p> <p>If these well-designed commercially-available systems are coupled with the other key socio-technical concepts required for safe and effective EHR implementation and use, and organizations have access to implementable clinical knowledge, we expect that the transformation of the healthcare enterprise that so many have predicted, is achievable using commercially-available, state-of-the-art EHRs.</p