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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

International audience; In 2014 leading publishers withdrew more than 120 nonsensical publications automatically generated with the SCIgen program. Casual observations suggested that similar problematic papers are still published and sold, without follow-up retractions. No systematic screening has been performed and the prevalence of such nonsensical publications in the scientific literature is unknown. Our contribution is 2-fold. First, we designed a detector that combs the scientific literature for grammar-based computer-generated papers. Applied to SCIgen, it has a 83.6% precision. Second, we performed a scientometric study of the 243 detected SCIgen-papers from 19 publishers. We estimate the prevalence of SCIgen-papers to be 75 per million papers in Information and Computing Sciences. Only 19% of the 243 problematic papers were dealt with: formal retraction (12) or silent removal (34). Publishers still serve and sometimes sell the remaining 197 papers without any caveat. We found evidence of citation manipulation via edited SCIgen bibliographies. This work reveals metric gaming up to the point of absurdity: fraudsters publish nonsensical algorithmically generated papers featuring genuine references. It stresses the need to screen papers for nonsense before peer-review and chase citation manipulation in published papers. Overall, this is yet another illustration of the harmful effects of the pressure to publish or perish.

The American Society for Parenteral and Enteral Nutrition (ASPEN) Position Paper focus is on applying the 4 ethical principles for clinician's decision-making in the use of artificially administered nutrition and hydration (AANH) for adult and pediatric patients. These basic principles are (1) autonomy, respect the patient's healthcare preferences; (2) beneficence, provide healthcare in the best interest of the patient; (3) nonmaleficence, do no harm; and (4) justice, provide all individuals a fair and appropriate distribution of healthcare resources. Preventing and resolving ethical dilemmas is addressed, with an emphasis on a collaborative, interdisciplinary approach. Optimizing early communication and promoting advance care planning, involving completion of an advance directive, including designation of a surrogate decision-maker, are encouraged. Clinicians achieve respect for autonomy when they incorporate the patient, family, community, country, geographical, and presumed cultural values and religious belief considerations into ethical decision-making for adults and children with a shared decision-making process. These discussions should be guided by the 4 ethical principles. Hospital committees and teams, limited-time trials, clinician obligation with conflicts, and forgoing of AANH are addressed. Specific patient conditions are addressed because of the concern for potential ethical issues: coma, decreased consciousness, and dementia; advanced dementia; cancer; eating disorders; and end-stage disease/terminal illness. Incorporated in the Position Paper are ethical decisions during a pandemic and a legal summary involving ethical issues. International authors presented the similarities and differences within their own country or region and compared them with the US perspective.

Perinatal depression can have enduring adverse effects on women and their children and families, incurring substantial ongoing economic and personal costs. A significant proportion of the cost of perinatal depression relates to adverse impacts on the child, most likely mediated through impairment to the mother-infant relationship. In recognition of this problem, Australia has invested in routine perinatal depression screening. Our previous research produced convergent findings suggesting that expected benefits for children have not yet been realised through perinatal depression screening. We question the potential of including a measure of personality in current perinatal depression screening for identifying maternal mental health problems and suboptimal mother-infant relationships. This paper reviews our previous research findings within the broader context of perinatal depression screening. We propose a position, that perinatal depression screening in Australia should be redesigned to more precisely detect vulnerable mother-infant relationships, parenting, maternal mental health, and infant psychosocial and psychological development. Practice change to appropriately target antenatal interventions may more efficiently improve both maternal and child outcomes, thereby contributing to greater efficiency and cost savings for the health system.

Silage quality remains an important issue in farming, as do limitations in the range of products suitable for animal fodder. We therefore explored the microorganisms that are critical for the fermentation quality of paper mulberry silage. Low (unwilted) and high (wilted) dry matter (DM) paper mulberry were harvested at two cutting times. These were ensiled for 0, 3, 7, 14, and 56 days, respectively. Compared with unwilted silages, wilting significantly decreased (p

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings togetherall the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs andhighlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactionsin the course of the disease.

Coronavirus disease 2019 (COVID‐19) first emerged in China in November 2019. Most governments have responded to the COVID‐19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID‐19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID‐19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID‐19 era (group activities, telemedicine, outpatients treatment, alcohol‐related liver disease and liver transplantation, collecting samples); (d) AUD and SARS‐CoV‐2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID‐19 disease will need implementation. Thus, the COVID‐19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in‐depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment., All health care systems need to be reorganized during and after the COVID‐19 pandemic, and also the CAATs in order to combine operator safety with patient safety and care. The multi‐disciplinary intervention involving experts in the treatment of AUD and ALD with specialists in the treatment of COVID‐19 disease will need implementation and the contribution of the family and of care‐givers in the management of AUD and ALD patients will play a significant role.

This article examines the joint makulatura campaign of 1974–91 by the Soviet Supply Committee (Gossnab) and the State Committee for Publishing (Goskomizdat), a campaign in which readers could exchange collected wastepaper for vouchers to obtain the popular and otherwise unavailable titles of the makulatura book series. Through analysis of the debate in Literaturnaia gazeta on the perceived waste and shortage of printing paper, the official campaign instructions, and the changing “editorial” paratexts of the makulatura books, the article sheds light on the public negotiations about the campaign and the value and reuse value of paper and reading matter in late Soviet society. By materializing the abstract relation between paper and books, the makulatura experiment turned both paper scrap and books into collection items and readers into paper suppliers. This materialization gave both readers and writers a marked awareness of paper as a raw material and a medium of cultural production. However, the shift of readers from the receiver to the producer side of the textual communication circuit also implied a collision of logics from the different perspectives of authors, collectors, publishers, and supply agencies.

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development. ispartof: BRITISH JOURNAL OF CLINICAL PHARMACOLOGY vol:88 issue:12 pages:4965-4984 ispartof: location:England status: published

The greatest challenge for European drug policies is how to effectively respond to the dynamic and constantly changing market for new psychoactive substances (NPS). Even small modifications in the chemical structure of substances often allow circumventing existing laws. Also in prison, the consumption of NPS is rising and there is growing evidence that NPS are responsible for a large share of drug-related problems. Ion mobility spectrometry (IMS) is the technique of choice for trace analysis of illicit drugs or explosives at security points, for example airports. Currently, databases of the reduced mobility (K0 ) values are limited to classical drugs and should be completed with data of emerging NPS. In this article, K0 values, LODs (0.7-3.6 ng) and drift times of 25 synthetic cannabinoids were evaluated. The data were added to existing databases of IMS which were then applied for fast screening in prison. The detection capability of the portable IMS technique was evaluated by the determination of intra-day (0.089%) and inter-day precision (0.004% to 0.14%), systematic error (0.19%), and separation capability for structurally related NPS. The applicability of the methodology was demonstrated by the successful analysis of 12 different pieces of paper impregnated with synthetic cannabinoids, 7 different cosmetics, and 5 food samples (liquids), spiked with a mixture of narcotic drugs and a synthetic cannabinoid. In addition, 14 herbal mixtures and 36 different casework samples from prisons were analyzed provided by the State Office of Criminal Investigation Rhineland-Palatinate (Germany).

Older adults account for 25% of all emergency department (ED) patient encounters. One in five Americans will be 65 or older by 2030. In response to this need, geriatric emergency medicine (GEM) has developed into a robust area of academic and clinical interest, with extensive evidence-based research and guidelines, including clear undergraduate and postgraduate GEM competencies. Despite these developments, GEM content remains underrepresented in curricula and licensing examinations. The complex reasons for these deficits include a perception that care of older adults is not a core emergency medicine (EM) competency, a disjunction between traditional definitions of expertise and the GEM perspective, and lack of curricular capacity. This White Paper, prepared on behalf of the Academy of Geriatric Emergency Medicine, describes the state of GEM education, identifies the challenges it faces, and reviews innovations, including research presented at the 2018 Society for Academic Emergency Medicine (SAEM) Annual Scientific Meeting. The authors propose a number of recommendations. These include recognizing GEM as a core educational priority in EM, enhancing academic support for GEM clinician-educators, using social learning and practical problem solving to teach GEM concepts, emphasizing a whole-person multisystem approach to care of older adults, and identifying ageist attitudes as a hurdle to safe and effective GEM care.

Open Dialogue is a need-adapted approach to mental health care that was originally developed in Finland. Like other need-adapted approaches, Open Dialogue aims to meet consumer’s needs and promote collaborative person-centred dialogue to support recovery. Need-adapted mental health care is distinguished by flexibility and responsiveness. Fidelity, defined from an implementation science perspective as the delivery of distinctive interventions in a high quality and effective fashion is a key consideration in health care. However, flexibility presents challenges for evaluating fidelity, which is much easier to evaluate when manualization and reproducible processes are possible. Hence, it remains unclear whether Open Dialogue and other need-adapted mental health interventions can be meaningfully evaluated for fidelity. The aim of this paper was to critically appraise and advance the evaluation of fidelity in need-adapted mental health care, using Open Dialogue as a case study. The paper opens a discussion about how fidelity should be evaluated in flexible, complex interventions, and identifies key questions that need to be asked by practitioners working in need-adapted mental health care to ensure they deliver these interventions as intended and in an evidence-based fashion.

Introduction. Drug checking services for harm reduction and overdose prevention have been implemented in many jurisdictions as a public health intervention in response to the opioid overdose crisis. This study demonstrates the first on-site use of paper spray mass spectrometry for quantitative drug checking to address the limitations of current on-site drug testing technologies. Methods. Paper spray mass spectrometry was used to provide on-site drug checking services at a supervised consumption site in the Downtown Eastside of Vancouver, British Columbia, Canada during a 2-day pilot test in August 2019. The method included the targeted quantitative measurement of 49 drugs and an untargeted full scan to assist in identifying unknown/unexpected components. Results. During the pilot, 113 samples were submitted for analysis, with 88 (78%) containing the client expected substance. Fentanyl was detected in 45 of 59 expected fentanyl samples, and in 50 (44%) samples overall at a median concentration of 3.6% (w/w%). The synthetic precursor of fentanyl, 4-anilino-N-phenethyl-piperidine (4-ANPP), was found in 74.0% of all fentanyl samples at a median concentration of 2.2%, suggesting widespread poor manufacturing practices. Etizolam was detected in 10 submitted samples anticipated to be fentanyl at a median concentration of 2.5%. No clients submitting these samples expected etizolam or a benzodiazepine in their sample. In three instances, it was co-measured with fentanyl, and in seven cases it was detected alone. Discussion and Conclusions. The quantitative capabilities and low detection limits demonstrated by paper spray mass spectrometry offer distinct benefits over existing on-site drug checking methods and harm reduction services. This work was supported by the Natural Science and Engineering Research Council of Canada Discovery Grant Program funding (RGPIN-2016-05380), Vancouver Island University and the Health Canada Drug Checking Technology Challenge. This article was originally published as: Borden, S.A., Saatchi, A., Vandergrift, G.W., Palaty, J., Lysyshyn, M., & Gill, C.G. (2021). A new quantitative drug checking technology for harm reduction: Pilot study in Vancouver, Canada using paper spray mass spectrometry. Drug and Alcohol Review, 1-8. https://doi.org/10.1111/dar.13370 This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. https://viurrspace.ca/bitstream/handle/10613/24515/Gill2021.pdf?sequence=3

The impact of COVID‐19 has underlined the need for reliable information to guide clinical practice and policy. This urgency has to be balanced against disruption to journal handling capacity and the continued need to ensure scientific rigour. We examined the reporting quality of highly disseminated COVID‐19 research papers using a bibliometric analysis examining reporting quality and risk of bias (RoB) amongst 250 top scoring Altmetric Attention Score (AAS) COVID‐19 research papers between January and April 2020. Method‐specific RoB tools were used to assess quality. After exclusions, 84 studies from 44 journals were included. Forty‐three (51%) were case series/studies, and only one was an randomized controlled trial. Most authors were from institutions based in China (n = 44, 52%). The median AAS and impact factor was 2015 (interquartile range [IQR] 1,105–4,051.5) and 12.8 (IQR 5–44.2) respectively. Nine studies (11%) utilized a formal reporting framework, 62 (74%) included a funding statement, and 41 (49%) were at high RoB. This review of the most widely disseminated COVID‐19 studies highlights a preponderance of low‐quality case series with few research papers adhering to good standards of reporting. It emphasizes the need for cautious interpretation of research and the increasingly vital responsibility that journals have in ensuring high‐quality publications.

The United States Environmental Protection Agency (EPA) developed Toxic Release Inventory (TRI) using information submitted by different industries in the United States. This research examines the contaminants released by paper manufacturing industry in the United States and Ohio over time and what paper manufacturers are doing to diminish the quantities of chemical wastes generated, released to the environment, or managed by other means. It is understood that there is a reduction in the Risk-Screening Environmental Indicators (RSEI) scores from 2002 to 2014 in all the states, which can be related to the adaptation of recycling or reusing of the chemicals in various other manufacturing processes. The other significant observation inferred from the analysis is that the facilities in the states such as Wisconsin, Louisiana, South Carolina, Connecticut, and Pennsylvania based on the economic feasibility or recycling prospects, they are generating higher quantities of the selected chemical resulting in the higher RSEI scores respectively for the above-mentioned states. This article demonstrates the application of the risk-screening indicators model to a large database to analyze pollution data. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 808–814, 2017

Machine learning, a branch of artificial intelligence, is increasingly used in health research, including nursing and maternal outcomes research. Machine learning algorithms are complex and involve statistics and terminology that are not common in health research. The purpose of this methods paper is to describe three machine learning algorithms in detail and provide an example of their use in maternal outcomes research. The three algorithms, classification and regression trees, least absolute shrinkage and selection operator, and random forest, may be used to understand risk groups, select variables for a model, and rank variables’ contribution to an outcome, respectively. While machine learning has plenty to contribute to health research, it also has some drawbacks, and these are discussed as well. In order to provide an example of the different algorithms’ function, they were used on a completed cross-sectional study examining the association of oxytocin total dose exposure with primary cesarean section. The results of the algorithms are compared to what was done or found using more traditional methods.

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender‐based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi‐square and Mann–Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011–2018 (n = 34) and ESMO in 2008–2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p, What's new? Presenting one's research at a conference is a great way to get your name and ideas heard within the professional community. In this study, the authors investigated how often women served as presenters at plenary sessions of ASCO Annual Meetings and ESMO Congresses. Looking through 166 abstracts over a period of 8 years, they found that 21% had female presenters, while 28% of study authors were female. Lack of visibility for female researchers at conferences can slow their career progress, and greater representation should be encouraged.

In this essay, I undertake a critical analysis of the UN-Habitat publication, The Quito Papers. I begin by unpacking the representation within The Quito Papers of the Charter of Athens of 1941 as an outcome of CIAM IV in 1933. Here, the ways in which the authors centralize the Charter of Athens within their critique of contemporary urbanization is critically analysed. Ultimately, I argue that what emerges is a simplification of the complex intertwining of urbanization and urbanist ideals. Based on this, I situate what is presented in The Quito Papers as alternative imaginaries?centred largely on European ideals of urbanism?within the context of urban change since the 1970s. This includes a discussion of the manner in which these ideals are promoted within urbanist discourse, including the role of the authors themselves in their engagement with UN-Habitat. Finally, I situate some of the arguments contained in The Quito Papers within current debates in urban theory. I contend that the relationship between processes of urbanization and the ideals of modernist urbanism are more genealogical than direct. Furthermore, I argue that it is through this relationship that broader power dynamics and their resultant inequalities can be further examined and challenged.

In recent years, it has been proposed that unrealistic requirements for academics and medical doctors to publish in scientific journals, combined with monetary publication rewards, have led to forms of contract cheating offered by organizations known as paper mills. Paper mills are alleged to offer products ranging from research data through to ghostwritten fraudulent or fabricated manuscripts and submission services. While paper mill operations remain poorly understood, it seems likely that paper mills need to balance product quantity and quality, such that they produce or contribute to large numbers of manuscripts that will be accepted for publication. Producing manuscripts at scale may be facilitated by the use of manuscript templates, which could give rise to shared features such as textual and organizational similarities, the description of highly generic study hypotheses and experimental approaches, digital images that show evidence of manipulation and/or reuse, and/or errors affecting verifiable experimental reagents. Based on these features, we propose practical steps that editors, journal staff, and peer reviewers can take to recognize and respond to research manuscripts and publications that may have been produced with undeclared assistance from paper mills.

Sixth generation will exploit satellite, aerial, and terrestrial platforms jointly to improve radio access capability and unlock the support of on-demand edge cloud services in three-dimensional (3D) space, by incorporating mobile edge computing (MEC) functionalities on aerial platforms and low-orbit satellites. This will extend the MEC support to devices and network elements in the sky and forge a space-borne MEC, enabling intelligent, personalized, and distributed on-demand services. End users will experience the impression of being surrounded by a distributed computer, fulfilling their requests with apparently zero latency. In this paper, we consider an architecture that provides communication, computation, and caching (C3) services on demand, anytime, and everywhere in 3D space, integrating conventional ground (terrestrial) base stations and flying (non-terrestrial) nodes. Given the complexity of the overall network, the C3 resources and management of aerial devices need to be jointly orchestrated via artificial intelligence-based algorithms, exploiting virtualized network functions dynamically deployed in a distributed manner across terrestrial and non-terrestrial nodes. European Union in the Horizon 2020 EU-Korea project 5G-ALLSTAR, GA no. 815323, by the Institute for Information & Communications Technology Promotion (IITP) grant funded by the Korean government (MSIT No. 2018-0-00175) and by Grant No. P102-18-27023S, funded by the Czech Science Foundation.

Motivation. The Panama Papers scandal highlighted the scale of financial secrecy, anonymous ownership and shell companies and their role in profit shifting and tax avoidance. We show the importance of international tax planning within the structure of corporate entities owned by shareholder‐individuals through Panama Papers destinations. Purpose. To identify profit‐shifting channels and to estimate related government revenue losses to European Union Member States. Methods. Using company data from the Amadeus/Orbis database (Bureau Van Dijk, n.d.a, n.d.b), we applied micro‐data analysis to the financial statements of multinational companies (MNEs) owned by shareholder‐individuals. Two groups—one with and the other without links to Panama Papers tax havens—alongside an analysis of profit‐shifting indicators. Findings. Profit is generally shifted by moving operating revenues or costs, though the use of debt channels is also important. Also, groups linked to tax havens pay significantly less tax per unit of profit before tax, and require less operating revenue to achieve higher profits. Finally, related government revenue losses were assessed at EUR 8.67 billion. Policy implication. Our results are relevant to the European Commission’s Comprehensive Common Consolidated Corporate Tax Base (CCCCTB) as it aims to counter profit shifting out of the European Union (EU) into tax havens. Further, our research highlights the importance of setting up registries of ultimate beneficiary owners in EU Member States.

International audience; The increasing number of frail elderly people in our aging society is becoming problematic: about 11% of community-dwelling older persons are frail and another 42% are pre-frail. Consequently, a major challenge in the coming years will be to test people over the age of 60 years to detect pre-frailty at the earliest stage and to return them to robustness using the targeted interventions that are becoming increasingly available. This challenge requires individual longitudinal monitoring (ILM) or follow-up of community-dwelling older persons using quantitative approaches. This paper briefly describes an effort to tackle this challenge. Extending the detection of the pre-frail stages to other population groups is also suggested. Appropriate algorithms have been used to begin the tracing of faint physiological signals in order to detect transitions from robustness to pre-frailty states and from pre-frailty to frailty states. It is hoped that these studies will allow older adults to receive preventive treatment at the correct institutions and by the appropriate professionals as early as possible, which will prevent loss of autonomy. Altogether, ILM is conceived as an emerging property of databases ("digital twins") and not the reverse. Furthermore, ILM should facilitate a coordinated set of actions by the caregivers, which is a complex challenge in itself. This approach should be gradually extended to all ages, because frailty has no age, as is testified by overwork, burnout, and post-traumatic syndrome.