University of Copenhagen

PAST: PALEONTOLOGICAL STATISTICAL SOFTWARE PACKAGE FOR EDUCATION AND DATA ANALYSIS

A comprehensive, but simple-to-use software package for executing a range of standard numerical analysis and operations used in quantitative paleontology has been developed. The program, called PAST (PAleontological STatistics), runs on standard Windows computers and is available free of charge. PAST integrates spreadsheet-type data entry with univariate and multivariate statistics, curve fitting, timeseries analysis, data plotting, and simple phylogenetic analysis. Many of the functions are specific to paleontology and ecology, and these functions are not found in standard, more extensive, statistical packages. PAST also includes fourteen case studies (data files and exercises) illustrating use of the program for paleontological problems, making it a complete educational package for courses in quantitative methods.

Assessing the Performance of Prediction Models

The performance of prediction models can be assessed using a variety of methods and metrics. Traditional measures for binary and survival outcomes include the Brier score to indicate overall model performance, the concordance (or c) statistic for discriminative ability (or area under the receiver operating characteristic [ROC] curve), and goodness-of-fit statistics for calibration.Several new measures have recently been proposed that can be seen as refinements of discrimination measures, including variants of the c statistic for survival, reclassification tables, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Moreover, decision-analytic measures have been proposed, including decision curves to plot the net benefit achieved by making decisions based on model predictions.We aimed to define the role of these relatively novel approaches in the evaluation of the performance of prediction models. For illustration, we present a case study of predicting the presence of residual tumor versus benign tissue in patients with testicular cancer (n = 544 for model development, n = 273 for external validation).We suggest that reporting discrimination and calibration will always be important for a prediction model. Decision-analytic measures should be reported if the predictive model is to be used for clinical decisions. Other measures of performance may be warranted in specific applications, such as reclassification metrics to gain insight into the value of adding a novel predictor to an established model.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium

The International Glossary on Infertility and Fertility Care, 2017

STUDY QUESTION: What updates of the International Glossary on Infertility and Fertility Care are required, to reflect contemporary scientific knowledge, social needs, and inclusive definitions, while harmonizing international communication across clinical, research, policy, and public domains? SUMMARY ANSWER: This 4th edition presents 348 consensus-based terms and definitions, including numerous revisions from the previous edition and 79 newly introduced definitions reflecting advances in reproductive science, technology, and evolving social contexts. WHAT IS KNOWN ALREADY: Previous glossary editions (2006, 2009, 2017) established internationally recognized definitions related to clinical practice, research, and policy. The 2017 edition comprised 283 terms and, among many others, expanded the concept of infertility to include not only its recognition as a disease, but also as an impairment of function generating disability. The glossary has been extensively used worldwide and has contributed to international standardization of data collection, appropriate comparison of outcome measures, and provided a reference for all stakeholders including policy makers. STUDY DESIGN, SIZE, DURATION: Under guidance of the organizing committee, 21 professionals from across the world, and representing expertise in different sub-specialties, formed five working groups: clinical definitions; outcome measures; embryology laboratory; clinical and laboratory andrology; and epidemiology, public health and gender related definitions. The definitions from the previous glossary were evaluated and new terms identified. All definitions were then reviewed by an international advisory panel of nine experts that evaluated the glossary from scientific, ethical, cultural, and policy perspectives. PARTICIPANTS/MATERIALS, SETTING, METHODS: Between November 2024 and October 2025, periodical virtual meetings were held within and between working groups and the organizing committee. Following circulation of the first consensually agreed draft, a one-day in-person meeting with representatives of all working groups and members of the international advisory panel was held at ESHRE, June 2025. Most terms and definitions were discussed and agreed. In the absence of agreement, further discussions were held between the organizing committee, working group chairs and members of the advisory panel. It had been determined at the outset that final disagreement would be resolved via a two-third majority vote. All terms and definitions were, however, reached by consensus and adopted following a final round of review and approval by all authors. MAIN RESULTS AND THE ROLE OF CHANCE: The glossary now includes 348 terms. Compared to the previous edition, 14 terms were deleted, numerous terms modified and 79 new terms were added. Modifications reflect current scientific knowledge, technological advancements, and inclusivity related to gender and family structures. Chance does not play a role, as all definitions are consensus-based. LIMITATIONS, REASONS FOR CAUTION: Some terms may require future refinement as scientific knowledge evolves and societal contexts change. The glossary reflects consensus rather than empirical testing of all definitions. WIDER IMPLICATIONS OF THE FINDINGS: This glossary provides a global reference for standardized terminology, supporting clinical care, research, international comparisons, policy making, patient communication, and reproductive health literacy. STUDY FUNDING/COMPETING INTEREST(S): Neither ICMART, responsible for conducting this project, nor any of the participants received specific financial support for their activities in this project. Ferring provided ICMART with a fixed amount to cover venue costs and a one-day hotel accommodation for participants attending the in-person meeting held prior to the ESHRE Congress in June 2025. Disclosures were provided by all authors, and none reported any conflict of interest related to this manuscript. TRIAL REGISTRATION NUMBER: N/A.

Applying evolutionary biology to address global challenges

BACKGROUND Differences among species in their ability to adapt to environmental change threaten biodiversity, human health, food security, and natural resource availability. Pathogens, pests, and cancers often quickly evolve resistance to control measures, whereas crops, livestock, wild species, and human beings often do not adapt fast enough to cope with climate change, habitat loss, toxicants, and lifestyle change. To address these challenges, practices based on evolutionary biology can promote sustainable outcomes via strategic manipulation of genetic, developmental, and environmental factors. Successful strategies effectively slow unwanted evolution and reduce fitness in costly species or improve performance of valued organisms by reducing phenotype-environment mismatch or increasing group productivity. Tactics of applied evolutionary biology range broadly, from common policies that promote public health or preserve habitat for threatened species—but are easily overlooked as having an evolutionary rationale, to the engineering of new genomes. ADVANCES The scope and development of current tactics vary widely. In particular, genetic engineering attracts much attention (and controversy) but now is used mainly for traits under simple genetic control. Human gene therapy, which mainly involves more complex controls, has yet to be applied successfully at large scales. In contrast, other methods to alter complex traits are improving. These include artificial selection for drought- and flood-tolerant crops through bioinformatics and application of “life course” approaches in medicine to reduce human metabolic disorders. Successful control of unwanted evolution depends on governance initiatives that address challenges arising from both natural and social factors. Principal among these challenges are (i) global transfer of genes and selection agents; (ii) interlinked evolution across traditional sectors of society (environment, food, and health); and (iii) conflicts between individual and group incentives that threaten regulation of antibiotic use and crop refuges. Evolutionarily informed practices are a newer prospect in some fields and require more systematic research, as well as ethical consideration—for example, in attempts to protect wild species through assisted migration, in the choice of source populations for restoration, or in genetic engineering. OUTLOOK A more unified platform will better convey the value of evolutionary methods to the public, scientists, and decision-makers. For researchers and practitioners, applications may be expanded to other disciplines, such as in the transfer of refuge strategies that slow resistance evolution in agriculture to slow unwanted evolution elsewhere (for example, cancer resistance or harvest-induced evolution). For policy-makers, adoption of practices that minimize unwanted evolution and reduce phenotype-environment mismatch in valued species is likely essential to achieve the forthcoming Sustainable Development Goals and the 2020 Aichi Biodiversity Targets.