BEATBOX v1.0: Background Error Analysis Testbed with Box Models

The Background Error Analysis Testbed (BEATBOX) is a new data assimilation framework for box models. Based on the BOX Model eXtension (BOXMOX) to the Kinetic Pre-Processor (KPP), this framework allows users to conduct performance evaluations of data assimilation experiments, sensitivity analyses, and detailed chemical scheme diagnostics from an observation simulation system experiment (OSSE) point of view. The BEATBOX framework incorporates an observation simulator and a data assimilation system with the possibility of choosing ensemble, adjoint, or combined sensitivities. A user-friendly, Python-based interface allows for the tuning of many parameters for atmospheric chemistry and data assimilation research as well as for educational purposes, for example observation error, model covariances, ensemble size, perturbation distribution in the initial conditions, and so on. In this work, the testbed is described and two case studies are presented to illustrate the design of a typical OSSE experiment, data assimilation experiments, a sensitivity analysis, and a method for diagnosing model errors. BEATBOX is released as an open source tool for the atmospheric chemistry and data assimilation communities

Prognostic impact of age and gender on patients with electrical storm

Background: Electrical storm (ES) is a severe and life-threatening heart rhythm disorder. Age and male gender have been identified as independent risk factors for cardiovascular diseases. However, data regarding the prognostic impact of age and gender on ES patients is limited. Methods: The present study included retrospectively consecutive patients presenting with ES from 2002 to 2016. Patients 67 years old or older were compared to patients younger than 67, males were also compared to females. Receiver operating characteristic analyses were performed to find the optimum age cut-off value. The primary endpoint was all-cause mortality at 3 years. The secondary endpoints were in-hospital mortality, rehospitalization rates, electrical storm recurrences (ES-R), and major adverse cardiac events (MACE) at 3 years. Results: Eighty-seven ES patients with implantable cardioverter-defibrillators were included. Age ≥ 67 years was associated with increased all-cause mortality at 3 years (48% vs. 20%, hazard ratio = 3.046; 95% confidence interval 1.316–7.051; p = 0.008; log-rank p = 0.006). MACE, in-hospital mortality, rehospitalization rates, and ES-R were not affected by age. Even after multivariate adjustment, age ≥ 67 years was associated with increased long-term mortality at 3 years, besides left ventricular ejection fraction < 35%. In contrast, gender was not associated with the primary and secondary endpoints. Conclusions: Patients 67 years old and older presenting with ES are associated with poor long-term prognosis at 3 years. Increased long-term mortality was still evident after multivariate adjustment. In contrast, gender was not associated with the primary and secondary endpoints

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions

Background: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). Methods: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. Results: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73–0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). Conclusion: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. Trial registration: NCT01535534. Registered 14.02.201

Does Albumin Predict the Risk of Mortality in Patients with Cardiogenic Shock?

This study investigates the prognostic impact of albumin levels in patients with cardiogenic shock (CS). Intensive care unit (ICU) related mortality in CS patients remains unacceptably high despite improvement concerning the treatment of CS patients. Limited data regarding the prognostic value of albumin in patients with CS is available. All consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from the day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. The prognostic impact of albumin was tested for 30-day all-cause mortality. Moreover, the prognostic performance of albumin decline during ICU treatment was examined. Statistical analyses included univariable t-test, Spearman’s correlation, Kaplan–Meier analyses, multivariable mixed analysis of variance (ANOVA), C-Statistics, and Cox proportional regression analyses. In total, 230 CS patients were included, with an overall all-cause mortality at 30 days of 54%. The median albumin on day 1 was 30.0 g/L. Albumin on day 1 was able to discriminate between 30-day survivors and non-survivors (area under the curve (AUC) 0.607; 0.535–0.680; p = 0.005). CS patients with albumin p = 0.016; HR = 1.517; 95% CI 1.063–2.164; p = 0.021), which was demonstrated even after multivariable adjustment. Moreover, a decrease of albumin levels by ≥20% from day 1 to day 3 was accompanied by a higher risk of 30-days all-cause mortality (56% vs. 39%; log-rank p = 0.036; HR = 1.645; 95% CI 1.014–2.669; p = 0.044). Especially when combined with lactate, creatinine, and cardiac troponin I, reliable discrimination of 30-day all-cause mortality was observed, including albumin in CS risk stratification models (AUC = 0.745; 95% CI 0.677–0.814; p = 0.001). In conclusion, low baseline albumin levels as well as a decay of albumin levels during the course of ICU treatment, deteriorate prognostic outcomes in CS patients. The additional assessment of albumin levels may further improve risk stratification in CS patients

Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015

The global diversity of HIV forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. We sought to determine country level HIV-1 diversity globally between 1990 and 2015. We assembled a global HIV-1 molecular epidemiology database through a systematic literature search and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from 1 January 1990 to 31 December 2015. We collected additional unpublished data through a global survey of experts. Prevalence studies with original HIV-1 subtyping data collected between 1990 and 2015 were included. This resulted in a database with 383,519 subtyped HIV-1 samples from 116 countries over four time periods (1990 to 1999, 2000 to 2004, 2005 to 2009, and 2010 to 2015). We analyzed country-specific numbers of distinct HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each time period. We also analyzed country-specific proportions of infections due to HIV-1 recombinants, CRFs, and URFs and calculated the Shannon diversity index for each country. Finally, we analyzed global temporal trends in each of these measures of HIV-1 diversity. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries such as Chad, Democratic Republic of the Congo, Angola, and Republic of the Congo have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe (Spain and France) and North America (United States) (up to 39 distinct HIV-1 variants in Spain). The proportion of HIV-1 infections due to recombinants was highest in Southeast Asia (>95% of infections in Viet Nam, Cambodia, and Thailand), China, and West and Central Africa, mainly due to high proportions of CRF01_AE and CRF02_AG. Other CRFs played major roles (>75% of HIV-1 infections) in Estonia (CRF06_cpx), Iran (CRF35_AD), and Algeria (CRF06_cpx). The highest proportions of URFs (>30%) were found in Myanmar, Republic of the Congo, and Argentina. Global temporal analysis showed consistent increases over time in country level numbers of distinct HIV-1 variants and proportions of CRFs and URFs, leading to increases in country level HIV-1 diversity. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to prevention and treatment efforts. HIV-1 molecular epidemiological surveillance needs to be continued and improved. IMPORTANCE This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays

Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis

BACKGROUND: Global genetic diversity of HIV-1 is a major challenge to the development of HIV vaccines. We aimed to estimate the regional and global distribution of HIV-1 subtypes and recombinants during 1990-2015. METHODS: We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published between Jan 1, 1990, and Dec 31, 2015. We collected additional unpublished HIV-1 subtyping data through a global survey. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. We grouped countries into 14 regions and analysed data for four time periods (1990-99, 2000-04, 2005-09, and 2010-15). The distribution of HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV (PLHIV) in each country to generate regional and global estimates of HIV-1 diversity in each time period. The primary outcome was the number of samples designated as HIV-1 subtypes A, B, C, D, F, G, H, J, K, CRFs, and URFs. The systematic review is registered with PROSPERO, number CRD42017067164. FINDINGS: This systematic review and global survey yielded 2203 datasets with 383 519 samples from 116 countries in 1990-2015. Globally, subtype C accounted for 46·6% (16 280 897/34 921 639 of PLHIV) of all HIV-1 infections in 2010-15. Subtype B was responsible for 12·1% (4 235 299/34 921 639) of infections, followed by subtype A (10·3%; 3 587 003/34 921 639), CRF02_AG (7·7%; 2 705 110/34 921 639), CRF01_AE (5·3%; 1 840 982/34 921 639), subtype G (4·6%; 1 591 276/34 921 639), and subtype D (2·7%; 926 255/34 921 639). Subtypes F, H, J, and K combined accounted for 0·9% (311 332/34 921 639) of infections. Other CRFs accounted for 3·7% (1 309 082/34 921 639), bringing the proportion of all CRFs to 16·7% (5 844 113/34 921 639). URFs constituted 6·1% (2 134 405/34 921 639), resulting in recombinants accounting for 22·8% (7 978 517/34 921 639) of all global HIV-1 infections. The distribution of HIV-1 subtypes and recombinants changed over time in countries, regions, and globally. At a global level during 2005-15, subtype B increased, subtypes A and D were stable, and subtypes C and G and CRF02_AG decreased. CRF01_AE, other CRFs, and URFs increased, leading to a consistent increase in the global proportion of recombinants over time. INTERPRETATION: Global and regional HIV diversity is complex and evolving, and is a major challenge to HIV vaccine development. Surveillance of the global molecular epidemiology of HIV-1 remains crucial for the design, testing, and implementation of HIV vaccines. FUNDING: None.status: publishe