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There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
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The nuclear matrix elements for the spin operator and the momentum quadrupole operator are important for the interpretation of precision atomic physics experiments that search for violations of local Lorentz and CPT symmetry and for new spin-dependent forces. We use the configuration-interaction nuclear shell model and self-consistent mean-field theory to calculate the momentum matrix elements for ^{21}Ne, ^{23}Na, ^{133}Cs, ^{173}Yb, and ^{201}Hg. We show that these momentum matrix are strongly suppressed by the many-body correlations, in contrast to the well-known enhancement of the spatial quadrupole nuclear matrix elements.
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Despite the more than 1 order of magnitude difference between the measured dipole moments in ^{144}Ba and ^{146}Ba, the octupole correlations in ^{146}Ba are found to be as strong as those in ^{144}Ba with a similarly large value of B(E3;3^{-}â0^{+}) determined as 48(+21-29) W.u. The new results not only establish unambiguously the presence of a region of octupole deformation centered on these neutron-rich Ba isotopes, but also manifest the dependence of the electric dipole moments on the occupancy of different neutron orbitals in nuclei with enhanced octupole strength, as revealed by fully microscopic calculations.
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This article reviews how nuclear fission is described within nuclear density functional theory. A distinction should be made between spontaneous fission, where half-lives are the main observables and quantum tunnelling the essential concept, and induced fission, where the focus is on fragment properties and explicitly time-dependent approaches are often invoked. Overall, the cornerstone of the density functional theory approach to fission is the energy density functional formalism. The basic tenets of this method, including some well-known tools such as the Hartree-Fock-Bogoliubov (HFB) theory, effective two-body nuclear potentials such as the Skyrme and Gogny force, finite-temperature extensions and beyond mean-field corrections, are presented succinctly. The energy density functional approach is often combined with the hypothesis that the time-scale of the large amplitude collective motion driving the system to fission is slow compared to typical time-scales of nucleons inside the nucleus. In practice, this hypothesis of adiabaticity is implemented by introducing (a few) collective variables and mapping out the many-body Schrödinger equation into a collective Schrödinger-like equation for the nuclear wave-packet. The region of the collective space where the system transitions from one nucleus to two (or more) fragments defines what are called the scission configurations. The inertia tensor that enters the kinetic energy term of the collective Schrödinger-like equation is one of the most essential ingredients of the theory, since it includes the response of the system to small changes in the collective variables. For this reason, the two main approximations used to compute this inertia tensor, the adiabatic time-dependent HFB and the generator coordinate method, are presented in detail, both in their general formulation and in their most common approximations. The collective inertia tensor enters also the Wentzel-Kramers-Brillouin (WKB) formula used to extract spontaneous fission half-lives from multi-dimensional quantum tunnelling probabilities (For the sake of completeness, other approaches to tunnelling based on functional integrals are also briefly discussed, although there are very few applications.) It is also an important component of some of the time-dependent methods that have been used in fission studies. Concerning the latter, both the semi-classical approaches to time-dependent nuclear dynamics and more microscopic theories involving explicit quantum-many-body methods are presented. One of the hallmarks of the microscopic theory of fission is the tremendous amount of computing needed for practical applications. In particular, the successful implementation of the theories presented in this article requires a very precise numerical resolution of the HFB equations for large values of the collective variables. This aspect is often overlooked, and several sections are devoted to discussing the resolution of the HFB equations, especially in the context of very deformed nuclear shapes. In particular, the numerical precision and iterative methods employed to obtain the HFB solution are documented in detail. Finally, a selection of the most recent and representative results obtained for both spontaneous and induced fission is presented, with the goal of emphasizing the coherence of the microscopic approaches employed. Although impressive progress has been achieved over the last two decades to understand fission microscopically, much work remains to be done. Several possible lines of research are outlined in the conclusion.
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OBJECTIVE: To understand the public policy-making process as it relates to breast cancer care in five Latin American countries. METHODS: An exploratory-evaluative study was conducted in Argentina, Brazil, Colombia, Mexico, and Venezuela in 2010, with the selection of countries based on convenience sampling. Sixty-five semi-structured interviews were conducted with government officials, academics, and representatives of trade associations and civil society organizations. A content analysis of secondary sources was performed. Information sources, data, and informants were mixed using the triangulation method for purposes of analysis. RESULTS: The countries that have made the most progress in public policy-making related to breast cancer are Brazil and Mexico. Although Argentina, Colombia, and Venezuela do not have policies, they do have breast cancer care programs and activities. Two perspectives on the development of public policies became evident: the first includes the broad participation of both governmental and nongovernmental sectors, whereas the second, more narrow approach involves government authorities alone. CONCLUSIONS: The results point to significant differences in public policy-making related to breast cancer in the Region. They also show that greater progress has been made in countries where policies have been developed through inclusive participation processes.
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Neoplasias da Mama/terapia , Política de Saúde , Feminino , Humanos , América LatinaRESUMO
We present a Pfaffian formula for projection and symmetry restoration for wave functions of the general Bogoliubov form, including quasiparticle excited states and linear combinations of them. This solves a long-standing problem in calculating states of good symmetry, arising from the sign ambiguity of the commonly used determinant formula. A simple example is given of projecting a good particle number and angular momentum from a Bogoliubov wave function in the Fock space of a single j-shell.
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Barker's hypothesis affirms that undernourishment in early-life induces metabolic reprogramming that compromises organism functions later in life, leading to age-related diseases. We are exposed to environmental and social conditions that impact our life trajectories, leading to ageing phenotypes as we grow. Epigenetic mechanisms constitute the link between both external stimuli and genetic programming. Studies have focused on describing the effect of early adverse events such as trauma, famines, or childhood labor on epigenetic markers in adulthood and the elderly. However, we lack information on epigenetic programming in individuals born in rural communities from underdeveloped countries, exposed to negative influences during fetal and postnatal development, particularly chronic malnutrition. Hence, in this exploratory analysis, we characterize the epigenome of individuals and some parents from Tlaltizapan (a rural community in Mexico originally studied almost 50 years ago) and collect anthropometric data on growth and development, as well on the living conditions of the families. Our results help build a biological hypothesis indicating that most of the epigenetic age measures of the subjects are significantly different among them. Interestingly, the most affected methylated regions correspond to pathways involved in neuronal system development, reproductive behaviour, learning and memory regulation.
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Metilação de DNA , Desnutrição , Estudos de Coortes , Epigênese Genética , Epigenômica , Humanos , Desnutrição/genética , População RuralRESUMO
Timely and accurate diagnosis of Alzheimer's disease (AD) in clinical practice remains challenging. PET and CSF biomarkers are the most widely used biomarkers to aid diagnosis in clinical research but present limitations for clinical practice (i.e., cost, accessibility). Emerging blood-based markers have the potential to be accurate, cost-effective, and easily accessible for widespread clinical use, and could facilitate timely diagnosis. The EU/US CTAD Task Force met in May 2022 in a virtual meeting to discuss pathways to implementation of blood-based markers in clinical practice. Specifically, the CTAD Task Force assessed: the state-of-art for blood-based markers, the current use of blood-based markers in clinical trials, the potential use of blood-based markers in clinical practice, the current challenges with blood-based markers, and the next steps needed for broader adoption in clinical practice.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Biomarcadores , Comitês ConsultivosRESUMO
OBJECTIVES: The aim of this study was to compare a short and a long version of an intrinsic capacity index and test their cross-sectional association with relevant health outcomes in older adults. DESIGN: Cross-sectional analysis of the baseline data of the FraDySMex study. PARTICIPANTS: 543 community-dwelling adults aged 50 years and older living in 2 municipalities in Mexico City, from which 435 had complete data on the variables of interest. METHODS: The intrinsic capacity indices were obtained using principal components analysis. The performance of the indices was tested respective to frailty, IADL and ADL. RESULTS: The short and long versions of the IC index performed well for assessing functional status. Using biometrical variables like the phase angle, grip strength and gait speed measured by the GAIT rite improved the index performance vis a vis IADL disability (Lawton), but not to the other evaluated outcomes. CONCLUSIONS: Both the long and short versions of the intrinsic capacity indices tested were able to classify older adults according to their functional status and were associated with relevant health outcomes.
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Fragilidade/epidemiologia , Vida Independente/normas , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , México , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.
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Envelhecimento/fisiologia , Exercício Físico , Fragilidade , Promoção da Saúde , Qualidade de Vida , Idoso , Exercício Físico/fisiologia , Terapia por Exercício/normas , Fragilidade/prevenção & controle , Humanos , Fenótipo , Comportamento SedentárioRESUMO
OBJECTIVES: Intrinsic capacity is a composite of five domains that summarizes the physical and mental capacities of an individual. Intrinsic capacity is increasing in relevance for adapting health systems to population ageing. Therefore, our objective was to analyse how intrinsic capacity has been assessed in older adults and if these measurements have been validated, as an initial step towards the construction of a standard intrinsic capacity index. DESIGN: Narrative review with electronic searches performed in PubMed and Cochrane databases, including the studies which used the term "intrinsic capacity" in the context of human ageing and health. The full text was then accessed to select studies with at least one operationalised domain of intrinsic capacity. We also looked for information on the validity and reliability of the reported measures of intrinsic capacity. RESULTS: We included ten articles reporting a quantitative measurement of intrinsic capacity. There were two intrinsic capacity scores which combined retrospective data on the intrinsic capacity domains sub-scores, with low concordance among tests chosen to measure each domain. Two studies reported on reliability and validity of the IC scores. The main gaps in the construction and validation process were a) analysis undertaken with each domain separately rather than for the construct of intrinsic capacity, b) lack of a clear conceptual and operational definition of the vitality domain, c) summary score that depends upon the distribution of the study sample. CONCLUSION: Further validation of the intrinsic capacity concept is needed, together with more robust approaches to measure it. A standard index of IC has not been validated for translation into clinical or research purposes.
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Saúde Pública/métodos , Padrões de Referência , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The aging process has been linked to the occurrence of chronic diseases and functional impairments, including cancer, sarcopenia, frailty, metabolic, cardiovascular, and neurodegenerative diseases. Nonetheless, aging is highly variable and heterogeneous and represents a challenge for its characterization. In this sense, intrinsic capacity (IC) stands as a novel perspective by the World Health Organization, which integrates the individual wellbeing, environment, and risk factors to understand aging. However, there is a lack of quantitative and qualitative attributes to define it objectively. Therefore, in this review we attempt to summarize the most relevant and promising biomarkers described in clinical studies at date over different molecular levels, including epigenomics, transcriptomics, proteomics, metabolomics, and the microbiome. To aid gerontologists, geriatricians, and biomedical researchers to understand the aging process through the IC. Aging biomarkers reflect the physiological state of individuals and the underlying mechanisms related to homeostatic changes throughout an individual lifespan; they demonstrated that aging could be measured independently of time (that may explain its heterogeneity) and to be helpful to predict age-related syndromes and mortality. In summary, we highlight the areas of opportunity and gaps of knowledge that must be addressed to fully integrate biomedical findings into clinically useful tools and interventions.
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Metabolômica , Proteômica , Envelhecimento , Biomarcadores , Epigenômica , HumanosRESUMO
OBJECTIVES: Intrinsic capacity (IC) is one of the latest views of positive aging. In its current status lacks a biological substrate amenable to be intervened. The aim of this study was to determine the association of allostatic load (AL) with IC. DESIGN: We present a cross-sectional analysis of the Costa Rican Longevity and Healthy Aging Study. SETTING: This report is from a representative sample of Costa Rican older adults; one of the countries that integrate the Central America region. PARTICIPANTS: 2,827, 60-year or older community-dwelling individuals. METHODS: An IC index was gathered and validated, including different domains: cognitive, psychological, sensory, vitality and locomotion. AL was integrated with: blood pressure, abdominal obesity, body mass index, HDL-cholesterol, glycosylated hemoglobin, DHEAS, cortisol, epinephrine and norepinephrine. AL was grouped in three categories according to the number of abnormal biomarkers (0-1, 2-3 and ≥4). Chronic diseases, socioeconomic level, sex and age were the adjusting variables. Ordinal logistic regression models were estimated in order to test the strength of the association. RESULTS: From a total sample of 1,888 individuals, 51% (n=962) were women, 36.4% were in the 60-69 age category. The mean score of the IC index was of 6.6 (±2.2). Odds ratio (OR) of the adjusted models were significant for the group of those with 2-3 abnormal biomarkers of AL (OR 0.67, p=0.007) and also for those with ≥4 (OR 0.56, p=0.002), when compared to the reference group of AL (0-1 abnormal biomarkers). CONCLUSIONS AND IMPLICATIONS: AL showed an incremental association with IC, even when adjusted for factors such as socioeconomic status and chronic diseases. Targeting therapeutically AL could potentially improve IC in older adults and therefore decreasing the progression to disability or to overt dependency.
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Envelhecimento/fisiologia , Alostase/fisiologia , Envelhecimento Saudável/fisiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , HDL-Colesterol/sangue , Doença Crônica , Estudos Transversais , Sulfato de Desidroepiandrosterona/sangue , Epinefrina/sangue , Feminino , Hemoglobinas Glicadas/análise , Hispânico ou Latino , Humanos , Hidrocortisona/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal , Razão de ChancesRESUMO
Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as FN1, APP, CREBBP, EGFR playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and -18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.
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Epigênese Genética/efeitos dos fármacos , Fragilidade/genética , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Fragilidade/tratamento farmacológico , Genes/efeitos dos fármacos , Genes/genética , Humanos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Farmacologia/métodos , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Biologia de Sistemas/métodosRESUMO
OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
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Fragilidade/diagnóstico , Fragilidade/terapia , Sarcopenia/diagnóstico , Sarcopenia/terapia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Exercício Físico/fisiologia , Humanos , Programas de Rastreamento/métodosRESUMO
OBJECTIVES: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR). METHODS: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit-harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process. RECOMMENDATIONS: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
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Programas de Rastreamento/métodos , Sarcopenia/diagnóstico , Sarcopenia/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Sarcopenia/patologiaRESUMO
INTRODUCTION: Calf circumference is a surrogate measurement of muscle mass. However, there is scarce evidence on its validity in predicting adverse outcomes such as mobility disability. The aim of this report is to determine if calf circumference could predict incident mobility disability in Mexican 60-year or older adults. METHODS: This is a secondary analysis of the Mexican Health and Aging Study and in particular of its two first waves. Sixty-year or older adults without mobility disability in the first assessment were included and followed-up for two years. Calf circumference quartile groups were compared to test the difference of incident mobility disability. Logistic regression models were fitted to test the independent association when including confounding variables. RESULTS: A total of 745 older adults were assessed, from which 24.4% of the older adults developed mobility disability at follow-up. A calf circumference > 38 cm was associated with a higher risk of developing mobility disability, even after adjustment in the multivariate model, with an odds ratio 0.55 (95% confidence interval 0.31-0.99, P = 0.049). CONCLUSIONS: High calf circumference in Mexican older adults is independently associated with incident mobility disability. This could reflect the impact of adverse health conditions such as obesity (with high fat tissue) or edema. Further research should aim at testing these results in different populations.
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BACKGROUND: The implementation of an aging biomarker into clinical practice is under debate. The Frailty Index is a model of deficit accumulation and has shown to accurately capture frailty in older adults, thus bridging biological with clinical practice. OBJECTIVES: To describe the association of socio-demographic characteristics and the Frailty Index in different age groups (from 20 to over one hundred years) in a representative sample of Mexican subjects. DESIGN: Cross-sectional analysis. SETTING: Nationwide and population-representative survey. PARTICIPANTS: Adults 20-years and older interviewed during the last Mexican National Health and Nutrition Survey (2012). MEASUREMENTS: A 30-item Frailty Index following standard construction was developed. Multi-level regression models were performed to test the associations of the Frailty Index with multiple socio-demographic characteristics across age groups. RESULTS: A total of 29,504 subjects was analyzed. The 30-item Frailty Index showed the highest scores in the older age groups, especially in women. No sociodemographic variable was associated with the Frailty Index in all the studied age groups. However, employment, economic income, and smoking status were more consistently found across age groups. CONCLUSIONS: To our knowledge, this is the first report describing the Frailty Index in a representative large sample of a Latin American country. Increasing age and gender were closely associated with a higher score.