To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA—associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

In this paper, a new multi-criteria problem solving method—the Full Consistency Method (FUCOM)—is proposed. The model implies the definition of two groups of constraints that need to satisfy the optimal values of weight coefficients. The first group of constraints is the condition that the relations of the weight coefficients of criteria should be equal to the comparative priorities of the criteria. The second group of constraints is defined on the basis of the conditions of mathematical transitivity. After defining the constraints and solving the model, in addition to optimal weight values, a deviation from full consistency (DFC) is obtained. The degree of DFC is the deviation value of the obtained weight coefficients from the estimated comparative priorities of the criteria. In addition, DFC is also the reliability confirmation of the obtained weights of criteria. In order to illustrate the proposed model and evaluate its performance, FUCOM was tested on several numerical examples from the literature. The model validation was performed by comparing it with the other subjective models (the Best Worst Method (BWM) and Analytic Hierarchy Process (AHP)), based on the pairwise comparisons of the criteria and the validation of the results by using DFC. The results show that FUCOM provides better results than the BWM and AHP methods, when the relation between consistency and the required number of the comparisons of the criteria are taken into consideration. The main advantages of FUCOM in relation to the existing multi-criteria decision-making (MCDM) methods are as follows: (1) a significantly smaller number of pairwise comparisons (only n − 1), (2) a consistent pairwise comparison of criteria, and (3) the calculation of the reliable values of criteria weight coefficients, which contribute to rational judgment.

Summary Background Up-to-date estimates of stroke burden and attributable risks and their trends at global, regional, and national levels are essential for evidence-based health care, prevention, and resource allocation planning. We aimed to provide such estimates for the period 1990–2021. Methods We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6–7·8] deaths; 10·7% [9·8–11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8–171·6] DALYs; 5·6% [5·0–6·1] of all DALYs). In 2021, there were 93·8 million (89·0–99·3) prevalent and 11·9 million (10·7–13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4–67·7), intracerebral haemorrhage constituted 28·8% (28·3–28·8), and subarachnoid haemorrhage constituted 5·8% (5·7–6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4–117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7–38·1]), diet high in sugar-sweetened beverages (23·4% [12·7–35·7]), low physical activity (11·3% [1·8–34·9]), high systolic blood pressure (6·7% [2·5–11·6]), lead exposure (6·5% [4·5–11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5–10·5]). Interpretation Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden. Funding Bill & Melinda Gates Foundation.

A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act. Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Aim To determine differences in physical activity level and functional fitness between young elderly (60–69 years) and old elderly (70–80 years) people with the hypothesis that an age-related decline would be found. Methods A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Results Significant differences (P < 0.05) were found for all Senior Fitness tests between young elderly (60–69 years) and old elderly (70–80) men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05). Conclusions This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.

BackgroundSince the emergence of social media in 2004, a growing percentage of patients use this technology for health related reasons. To reflect on the alleged beneficial and potentially harmful effects of social media use by patients, the aim of this paper is to provide an overview of the extant literature on the effects of social media use for health related reasons on patients and their relationship with healthcare professionals.MethodsWe conducted a systematic literature review on empirical research regarding the effects of social media use by patients for health related reasons. The papers we included met the following selection criteria: (1) published in a peer-reviewed journal, (2) written in English, (3) full text available to the researcher, (4) contain primary empirical data, (5) the users of social media are patients, (6) the effects of patients using social media are clearly stated, (7) satisfy established quality criteria.ResultsInitially, a total of 1,743 articles were identified from which 22 were included in the study. From these articles six categories of patients’ use of social media were identified, namely: emotional, information, esteem, network support, social comparison and emotional expression. The types of use were found to lead to seven identified types of effects on patients, namely improved self-management and control, enhanced psychological well-being, and enhanced subjective well-being, diminished subjective well-being, addiction to social media, loss of privacy, and being targeted for promotion. Social media use by patients was found to affect the healthcare professional and patient relationship, by leading to more equal communication between the patient and healthcare professional, increased switching of doctors, harmonious relationships, and suboptimal interaction between the patient and healthcare professional.ConclusionsOur review provides insights into the emerging utilization of social media in healthcare. In particular, it identifies types of use by patients as well as the effects of such use, which may differ between patients and doctors. Accordingly, our results framework and propositions can serve to guide future research, and they also have practical implications for healthcare providers and policy makers.

Abstract IoT (Internet of Things) is a new paradigm which provides a set of new services for the next wave of technological innovations. IoT applications are nearly limitless while enabling seamless integration of the cyber-world with the physical world. However, despite the enormous efforts of standardization bodies, alliances, industries, researchers and others, there are still numerous problems to deal with in order to reach the full potential of IoT. These issues should be considered from various aspects such as enabling technologies, applications, business models, social and environmental impacts. In focus of this paper are open issues and challenges considered from the technological perspective. Just for clarification, we put in light different visions that stand behind this paradigm in order to facilitate a better understanding of the IoT's features. Furthermore, this exhaustive survey provides insights into the state-of-the-art of IoT enabling and emerging technologies. The most relevant among them are addressed with some details. The main scope is to deliver a comprehensive overview of open issues and challenges to be tackled by future research. We provide some insights into specific emerging ideas in order to facilitate future research. Also, this paper brings order in the existing literature by classifying contributions according to different research topics.