PEDIA: prioritization of exome data by image analysis

Purpose Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Methods Here, we introduce an approach driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features, and the disease-causing variants, and simulated multiple exomes of different ethnic backgrounds. Results The additional use of similarity scores from computer-assisted analysis of frontal photos improved the top 1 accuracy rate by more than 20–89% and the top 10 accuracy rate by more than 5–99% for the disease-causing gene. Conclusion Image analysis by deep-learning algorithms can be used to quantify the phenotypic similarity (PP4 criterion of the American College of Medical Genetics and Genomics guidelines) and to advance the performance of bioinformatics pipelines for exome analysis

Properties of Neon, Magnesium, and Silicon Primary Cosmic Rays Results from the Alpha Magnetic Spectrometer

We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8 × 10$^{6}$ Ne, 2.2 × 10$^{6}$ Mg, and 1.6 × 10$^{6}$ Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays

The Alpha Magnetic Spectrometer (AMS) on the international space station: Part II — Results from the first seven years

The Alpha Magnetic Spectrometer (AMS) is a precision particle physics detector on the International Space Station (ISS) conducting a unique, long-duration mission of fundamental physics research in space. The physics objectives include the precise studies of the origin of dark matter, antimatter, and cosmic rays as well as the exploration of new phenomena. Following a 16-year period of construction and testing, and a precursor flight on the Space Shuttle, AMS was installed on the ISS on May 19, 2011. In this report we present results based on 120 billion charged cosmic ray events up to multi-TeV energies. This includes the fluxes of positrons, electrons, antiprotons, protons, and nuclei. These results provide unexpected information, which cannot be explained by the current theoretical models. The accuracy and characteristics of the data, simultaneously from many different types of cosmic rays, provide unique input to the understanding of origins, acceleration, and propagation of cosmic rays

Properties of Iron Primary Cosmic Rays: Results from the Alpha Magnetic Spectrometer

We report the observation of new properties of primary iron (Fe) cosmic rays in the rigidity range 2.65 GV to 3.0 TV with 0.62 million iron nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. Above 80.5 GV the rigidity dependence of the cosmic ray Fe flux is identical to the rigidity dependence of the primary cosmic ray He, C, and O fluxes, with the Fe/O flux ratio being constant at 0.155±0.006. This shows that unexpectedly Fe and He, C, and O belong to the same class of primary cosmic rays which is different from the primary cosmic rays Ne, Mg, and Si class

Factors associated with smoking among tuberculosis patients in Spain

BACKGROUND: To determine the prevalence of smoking and analyze associated factors in a cohort of patients diagnosed with tuberculosis (TB) in Spain between 2006 and 2013. METHODS: Multicenter, cross-sectional, descriptive, observational study using a national database of TB patients, using logistic regression to calculate odds ratios (OR) and confidence intervals (CI). RESULTS: We analyzed 5,846 cases (62 % men, mean age 39 years, 33 % foreigners). 23.4 % were alcohol abuser, 1.3 % were injected drug users (IDU), 4.6 % were co-infected with HIV, and 7.5 % had a history of TB treatment. 6.6 % and 0.8 % showed resistance to one and multiple drugs, respectively. The predominant clinical presentation was pulmonary (71 %) with a cavitary radiological pattern in 32.8 % of cases. 82 % of cases were confirmed microbiologically, and 54 % were smear-positive microscopy. 2,300 (39.3 %) patients were smokers. The following factors were associated with smoking: male sex (OR = 2.26;CI:1.97;2.60), Spanish origin (OR = 2.79;CI:2.40–3.24), alcoholism (OR = 2.85;CI:2.46;3.31), IDU (OR = 2.78;CI:1.48;5.52), homelessness (OR = 1.99;CI:1.14–3.57), pulmonary TB (OR = 1.61;CI:1.16;2.24), cavitary radiological pattern (OR = 1.99;CI:1.43;2.79) and a smear-positive microscopy at the time of diagnosis (OR = 1.39;CI:1.14;1.17). CONCLUSIONS: The prevalence of smoking among TB patients is high. Smokers with TB have a distinct sociodemographic, clinical, radiological and microbiological profile to non-smokers

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Budgetary impact analysis on funding smoking-cessation drugs in patients with COPD in Spain

Carlos A Jiménez-Ruiz,1 Segismundo Solano-Reina,2 Jaime Signes-Costa,3 Eva de Higes-Martinez,4 José I Granda-Orive,5 José J Lorza-Blasco,6 Juan A Riesco-Miranda,7 Neus Altet-Gomez,8 Miguel Barrueco,9 Itziar Oyagüez,10 Javier Rejas11 On behalf of the SEPAR’s Integrated Tobacco Research Program 1Specialised Tobacco Unit, Community of Madrid, 2Tobacco Unit, Department of Pulmonary Medicine, Hospital General Universitario Gregorio Marañón, Madrid, 3Department of Pulmonary Medicine, Hospital Universitario San Juan, Alicante, 4Department of Pulmonary Medicine, Hospital Universitario Fundación Alcorcón, 5Department of Pulmonary Medicine, Hospital Universitario 12 de Octubre, Madrid, 6Department of Pulmonary Medicine, Complejo Hospitalario de Navarra, Pamplona, Navarre, 7Department of Pulmonary Medicine, Hospital de San Pedro Alcántara, Cáceres, 8Drassanes Tobacco Unit, Hospital Universitari Vall-d’Hebron-Drassanes, The Jordi Gol University Institute for Research Primary Healthcare, Barcelona, 9Department of Pulmonary Medicine, Hospital Universitario de Salamanca, Biomedical Research Institute, Salamanca, 10Pharmacoeconomics & Outcomes Research Iberia, 11Department of Pharmacoeconomics and Health Outcomes Research, Pfizer, Sociedad Limitada Unificada, Alcobendas, Madrid, Spain Abstract: The aim of the study was to assess the budgetary impact of funding smoking-cessation drugs in COPD patients in Spain. A hybrid model (cohort and Markov) was developed for a 5-year time horizon. Only approved cessation drugs (varenicline, bupropion, and nicotine replacement therapy) were considered. Irrespective of the drug, the model allowed for an initial cessation attempt, and up to three additional attempts in case of failure or smoking relapse during a 5-year period. Drug effectiveness was based on controlled clinical trials. National Health System perspective was applied; therefore, only medical resources were included. The pharmaceutical costs for smoking-cessation drugs, extra medical follow-up as a consequence of public reimbursement, and annual savings for health costs avoided due to stopping smoking were considered. The model estimated that 17,756 COPD patients would stop smoking if public funding was available, compared with 1,303 without reimbursement. In the reimbursement scenario, the savings accounted for a total of €48.0 million, compensating for expenditures on drugs and medical visits (€40.4 million). Accumulated total additional savings in 5 years (€4.3 million) compared with the scenario without reimbursement was shown. Sensitivity analyses supported the results robustness. Funding smoking-cessation drugs in COPD patients seems to be an efficient option and a National Health System drug reimbursement scheme would represent a cost-saving policy in Spain. Keywords: pharmacotherapy, COPD, smoking cessation, budgetary impact, health servic