The burden of injury in Central, Eastern, and Western European sub-region : a systematic analysis from the Global Burden of Disease 2019 Study

Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.Peer reviewe

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Electron beam exciter for optical emission spectroscopy and optical excitation cross section analysis in processing systems

Plasma processing technology is indispensable for manufacturing the very large scale integrated circuits (ICs) used by the electronics industry. 48 Generally, the precise control and characterization of the plasma processing medium becomes pivotal to develop a successful product. At present, a variety of complementary characterization techniques are providing precise and detailed information on a variety of processing plasmas. However, newer generations of plasma processing techniques are becoming far too complex and their operating conditions impose great limitations on the operability and functionality of many important diagnostics. To adapt to these new set of constraints, the present work focuses on the development of a new Electron Beam Exciter device designed to conduct quantitative optical measurements in processing systems. This newly developed Exciter prototype employs a highly controllable electron beam of controlled energy level (Ee = 1/2 mv2) and density (n e) to cause light emission from electron-impact excitation events with gas particles that are part of the chemical makeup characterizing the processing environment. As such, the current design utilizes an inductively coupled plasma (ICP) source (RF coil antenna, 29 MHz) to generate a continuous cloud of electrons that can be extracted to an excitation region where optical and electrical measurements are collected. This variable plasma source, or electron bottle, is made out of a quartz or sapphire tube and is positioned opposite to an electron extraction assembly (or accelerator assembly), so that plasma electrons are extracted from the source via controlled dc electric potentials. The electron extraction assembly is composed of three distinct electrodes, namely the nozzle extractor, an extractor plate and a Faraday cup electrode, and is protected by a Tin doped Indium Oxide (ITO) interface that allows device operability in harsh halide enriched environments. Furthermore, the ability to successfully control the electron energy distribution function (EEDF) and energy level (Ee) characterizing the extracted electron beams allows the measurement of optical excitation cross-section from several reactive plasma effluents, some of which have not been measured before. The distinctiveness of the system with such a measurement capability to real time diagnostics, and its usefulness to measure cross sections of molecular species from plasmas are discussed

ARTICULO DE REVISION / REVIEW ARTICLE - METODOS ESPECTROMETRICOS DE MASAS PARA EL ESTUDIO DE PROTEINAS

The development of new ionization methods has allowed the establishment of mass spectrometry as analytical tool for the characterization of biomolecules, becoming an essential technique for the detection of modified amino acids in natural and recombinant proteins. Besides, this technique constitute a promising alternative for peptide and protein sequencing. Here, we describe the development of this technique in the last 20 years and the most advanced equipments nowadays used for protein studies. RESUMEN El desarrollo de nuevos metodos de ionizacion ha permitido a la espectrometria de masas establecerse como tecnica de analisis de biomoleculas. Actualmente constituye una tecnica insustituible para la deteccion de aminoacidos modificados en proteinas naturales y recombinantes y una alternativa prometedora para la secuenciacion de peptidos y proteinas. En este trabajo se describe el desarrollo de esta tecnica en los ultimos 20 anos y la instrumentacion mas empleada actualmente para el estudio de proteinas. Desde la decada del 50, la espectrometria de masas (EM) era ya una reconocida herramienta en la elucidacion de estructuras de compuestos organicos(1), caracterizada por una alta exactitud en las mediciones y una alta sensibilidad. Sin embargo, hasta la decada del 80 la contribucion de esta tecnica a la elucidacion de la estructura primaria de las proteinas fue limitada(2, 3), pues aun para peptidos pequenos se requiere de una extensa derivacion (para conferirles volatilidad) y de sucesivos pasos de extraccion o purificacion del derivado. Estas razones, hicieron impracticable esta tecnica como via para la secuenciacion de proteinas de forma rutinaria. En los ultimos anos se han logrado dos avances importantes que permiten la aplicacion progresiva de la espectrometria de masas a las biomoleculas y en particular a las proteinas. En primer lugar, el diseno de novedosos metodos de ionizacion y en segundo lugar, la introduccion de mejoras tecnologicas en los analizadores ya existentes

REPORTE CORTO / SHORT REPORT - INFLUENCE OF BASIC RESIDUES ON THE C-TERMINAL REARRANGEMENT OF PEPTIDES IN GAS PHASE

We designed and synthesized a set of peptides in order to study some factors that could affect the appearance of this fragmentation such as the position of the basic residue within the sequence, the nature of the amino acids involved in the rearrangement and the way in wich the different basicity of two isobaric amino acids such as lysine and glutamine could be helpful to differentiate them taking into account the intensities ratio of bn-1/bn-1+1

x-ray investigation of a recombinant outer membrane protein from Neisseria meningitidis

no abstrac

ARTICULO ORIGINAL CORTO / SHORT ORIGINAL PAPER - HIGH LEVEL EXPRESSION OF HUMAN IFN-alpha2b IN Pichia Pastoris

The gene coding for human interferon-alpha2b was integrated into the Pichia pastoris genome. The expression of the interferon gene was controlled by methanol-regulated alcohol oxidase (AOX1) promoter. An expression level of 400 mg of interferon per liter of culture was achieved under appropriate fermentation conditions. The molecule was purified to homogeneity and partially characterized in terms of biological activity and structural properties. Fast Atom Bombardment Mass Spectrometry (FAB-MS) allowed the verification of the aminoacid sequence and indicated the presence of amino-terminal acetyl groups in 70% of the final product. An alternative to eliminate this modification is suggested. RESUMEN El gen que codifica para el interferon-alfa 2b humano fue integrado en el genoma de Pichia pastoris. La expresion del gen de interferon fue controlada por la induccion con metanol del promotor alcohol oxidasa 1. Se alcanzaron 400 mg de interferon por litro de cultivo en fermentacion. La molecula fue purificada y parcialmente caracterizada. Se verifico la secuencia aminoacidica por espectrometria de masas con ionizacion por bombardeo con atomos acelerados (FAB-MS) detectandose un 70% de acetilacion. Una alternativa para eliminar esta modificacion es propuesta