Gas-phase formation of glycolonitrile in the interstellar medium

Our automated reaction discovery program, AutoMeKin, has been utilized to investigate the formation of glycolonitrile (HOCH$_{2}$CN) in the gas phase under the low temperatures of the interstellar medium (ISM). The feasibility of a proposed pathway depends on the absence of barriers above the energy of reactants and the availability of the suggested precursors in the ISM. Based on these criteria, several radical-radical reactions and a radical-molecule reaction have been identified as viable formation routes in the ISM. Among the radical-radical reactions, OH+CH$_{2}$CN appears to be the most relevant, considering the energy of the radicals and its ability to produce glycolonitrile in a single step. However, our analysis reveals that this reaction produces hydrogen isocyanide (HNC) and formaldehyde (CH$_{2}$O), with rate coefficients ranging from (7.3-11.5)$\times$10$^{-10}$ cm$^3$ molecule$^{-1}$ s$^{-1}$ across the temperature range of 10-150 K. This finding is particularly interesing given the persistently unexplained overabundance of hydrogen isocyanide in the ISM. Among the radical-molecule reactions investigated, the most promising one is OH+CH$_{2}$CNH, which forms glycolonitrile and atomic hydrogen with rate coefficients in the range (0.3-6.6)$\times$10$^{-10}$ cm$^3$ molecule$^{-1}$ s$^{-1}$ within the 10-150 K temperature range. Our calculations indicate that the formation of both hydrogen isocyanide and glycolonitrile is efficient under the harsh conditions of the ISM

Breast Cancer Detection by Means of Artificial Neural Networks

Breast cancer is a fatal disease causing high mortality in women. Constant efforts are being made for creating more efficient techniques for early and accurate diagnosis. Classical methods require oncologists to examine the breast lesions for detection and classification of various stages of cancer. Such manual attempts are time consuming and inefficient in many cases. Hence, there is a need for efficient methods that diagnoses the cancerous cells without human involvement with high accuracies. In this research, image processing techniques were used to develop imaging biomarkers through mammography analysis and based on artificial intelligence technology aiming to detect breast cancer in early stages to support diagnosis and prioritization of high-risk patients. For automatic classification of breast cancer on mammograms, a generalized regression artificial neural network was trained and tested to separate malignant and benign tumors reaching an accuracy of 95.83%. With the biomarker and trained neural net, a computer-aided diagnosis system is being designed. The results obtained show that generalized regression artificial neural network is a promising and robust system for breast cancer detection. The Laboratorio de Innovacion y Desarrollo Tecnologico en Inteligencia Artificial is seeking collaboration with research groups interested in validating the technology being developed

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

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

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Actions for the generation of a community organization manual: the case of the urban area Montería

El propósito de este artículo fue proponer un manual para las organizaciones comunitarias del área urbana de la ciudad de Montería partiendo del desarrollo de tres objetivos específicos, el primero encaminado a diagnosticar el estado actual  de las organizaciones comunitarias a partir del análisis de las mismas y de las percepciones que poseen algunos actores sociales e institucionales, el segundo propósito consistente en determinar los elementos constitutivos del manual y por último, la generación del manual en sí. De la fase diagnostica, se señala que por una parte el nivel de formación de los líderes comunales es deficiente, un 56% solo tiene estudios básicos. Adicionalmente, las organizaciones comunales carecen del enfoque y conocimiento de la gestión ambiental local, también  la percepción que se tiene desde lo público y lo privado acerca de este tipo de instituciones no es muy favorable, sin omitir que las JAC son consideradas como parte de la maquinaria politiquera de la región. Así mismo, como principales debilidades al interior de sus estructuras se encuentran la falta de compromiso y responsabilidad de los miembros para con éstas. Dentro de los elementos constitutivos del manual se identificaron 6 componentes, dos de carácter complementario (Ciclo Planear, Hacer, Verificar y Actuar, además de los enfoques: sistémico, holístico y de desarrollo sostenible) y cuatro como ejes centrales (perfil del territorio, estructura comunitaria, cualificación a organizaciones sociales y mediación para la solución de problemas ambientales). Desde el análisis de los elementos en cuestión se procedió a generar el manual con todas las relaciones dada para cada uno de ellos.The purpose of this paper was to propose a manual for community organizations of the urban area of the city of Monteria, from the development of three specific objectives, the first aimed at diagnosing the current state of community organizations from the analysis of the organization itself and perceptions of some social and institutional actors, the second of determining the constituent elements of the manual and finally the generation of the manual itself. Phase diagnosed States that on the one hand the level of training  of community leaders in poor, only 56% have basic studies. On the other hand, community organizations lack focus and knowledge of local environmental management and the perception that it’s from public and private about this type of institutions is not very favorable, without omitting the JAC are considered part of the politiquera machinery in the region. Also, as major weaknesses within their structures are the lack of commitment and responsibility of members to with them. And four as central (profile of the territory structure: Within the constituent elements of the manual six components, two complementary (systemic, holistic and sustainable development cycle Plan-Do-Check-Act, in addition to approaches) were identified Community, social skills and mediation organizations to solve environmental problems). From the analysis of the elements in question it proceeded to build the manual with all relationships given for each of them