Predictive ability of heel quantitative ultrasound for incident fractures: an individual-level meta-analysis.

UNLABELLED: The relationship between bone quantitative ultrasound (QUS) and fracture risk was estimated in an individual level data meta-analysis of 9 prospective studies of 46,124 individuals and 3018 incident fractures. Low QUS is associated with an increase in fracture risk, including hip fracture. The association with osteoporotic fracture decreases with time. INTRODUCTION: The aim of this meta-analysis was to investigate the association between parameters of QUS and risk of fracture. METHODS: In an individual-level analysis, we studied participants in nine prospective cohorts from Asia, Europe and North America. Heel broadband ultrasonic attenuation (BUA dB/MHz) and speed of sound (SOS m/s) were measured at baseline. Fractures during follow-up were collected by self-report and in some cohorts confirmed by radiography. An extension of Poisson regression was used to examine the gradient of risk (GR, hazard ratio per 1 SD decrease) between QUS and fracture risk adjusted for age and time since baseline in each cohort. Interactions between QUS and age and time since baseline were explored. RESULTS: Baseline measurements were available in 46,124 men and women, mean age 70 years (range 20-100). Three thousand and eighteen osteoporotic fractures (787 hip fractures) occurred during follow-up of 214,000 person-years. The summary GR for osteoporotic fracture was similar for both BUA (1.45, 95 % confidence intervals (CI) 1.40-1.51) and SOS (1.42, 95 % CI 1.36-1.47). For hip fracture, the respective GRs were 1.69 (95 % CI, 1.56-1.82) and 1.60 (95 % CI, 1.48-1.72). However, the GR was significantly higher for both fracture outcomes at lower baseline BUA and SOS (p < 0.001). The predictive value of QUS was the same for men and women and for all ages (p > 0.20), but the predictive value of both BUA and SOS for osteoporotic fracture decreased with time (p = 0.018 and p = 0.010, respectively). For example, the GR of BUA for osteoporotic fracture, adjusted for age, was 1.51 (95 % CI 1.42-1.61) at 1 year after baseline, but at 5 years, it was 1.36 (95 % CI 1.27-1.46). CONCLUSIONS: Our results confirm that quantitative ultrasound is an independent predictor of fracture for men and women particularly at low QUS values.

Una referencia conceptual para la disciplina

Es comprensible que cuando hablamos de los diagnósticos enfermeros se produzcan confusiones terminológicas puesto que, según el Diccionario de la Real Academia de la Lengua Española, la primera acepción de la palabra diagnóstico es «perteneciente o relativo a la diagnosis. Conjunto de signos que sirven para fijar la naturaleza de una enfermedad». Por tanto, debemos...

Professional trajectories, individual characteristics and staying satisfied and healthy

Staying satisfied and healthy in the face of a complex and uncertain professional world is a priority for individuals. This article examines the contribution of personality traits, career adaptability, and prior well-being as predictors of well-being over 1 year in four different professional trajectory groups: those who remained employed, those who experienced a professional change, those who moved from unemployment to employment, and those who remained unemployed. Results show meaningful differences between these groups in terms of well-being over 1 year. Employed individuals have higher life satisfaction and self-rated health than unemployed individuals. Regaining employment contributes to improved well-being. Different professional situations correspond to varying levels of career adaptability, suggesting it may be a precursor for career changes. Personality traits and career adaptability predict well-being over time, but the strongest predictor of future well-being is prior well-being. Results are discussed in light of career development, personality, and well-being theory.

Singling out individual inventors from patent data

An increasing number of studies in recent years have sought to identify individual inventors from patent data. A variety of heuristics have been proposed for using the names and other information disclosed in patent documents to establish who is who in patents. This paper contributes to this literature by describing a methodology for identifying inventors using patents applied to the European Patent Office, EPO hereafter. As in much of this literature, we basically follow a threestep procedure : 1- the parsing stage, aimed at reducing the noise in the inventor’s name and other fields of the patent; 2- the matching stage, where name matching algorithms are used to group similar names; and 3- the filtering stage, where additional information and various scoring schemes are used to filter out these similarlynamed inventors. The paper presents the results obtained by using the algorithms with the set of European inventors applying to the EPO over a long period of time.

Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.

Cytotoxic T cells recognize, via their T cell receptors (TCRs), small antigenic peptides presented by the major histocompatibility complex (pMHC) on the surface of professional antigen-presenting cells and infected or malignant cells. The efficiency of T cell triggering critically depends on TCR binding to cognate pMHC, i.e., the TCR-pMHC structural avidity. The binding and kinetic attributes of this interaction are key parameters for protective T cell-mediated immunity, with stronger TCR-pMHC interactions conferring superior T cell activation and responsiveness than weaker ones. However, high-avidity TCRs are not always available, particularly among self/tumor antigen-specific T cells, most of which are eliminated by central and peripheral deletion mechanisms. Consequently, systematic assessment of T cell avidity can greatly help distinguishing protective from non-protective T cells. Here, we review novel strategies to assess TCR-pMHC interaction kinetics, enabling the identification of the functionally most-relevant T cells. We also discuss the significance of these technologies in determining which cells within a naturally occurring polyclonal tumor-specific T cell response would offer the best clinical benefit for use in adoptive therapies, with or without T cell engineering.

Innovation – from individual intuition to collaborative innovation. The role of individual key actor in facilitation of innovation in large organization context

The objective of this research was to study the role of key individuals in facilitation of technology enabled bottom-up innovation in large organization context. The development of innovation was followed from the point of view of individual actor (key individual) in two cases, through three levels: individual, team and organization, by using knowledge creation and innovation models. This study provides theoretical synthesis and framework through which the study is driven. The results of the study indicate, that in bottom-up initiated innovations the role of key individuals is still crucial, but innovation today is collective effort and there acts several entrepreneurial key individuals: innovator, user champion and organizational sponsor, whose collaboration and developing interaction drives innovation further. The team work is functional and fluent, but it meets great problems in interaction with organization. The large organizations should develop its practices and ability to react on emerging bottom-up initiations, in order to embed innovation to organization and gain sustainable innovation. In addition, bottom-up initiated innovations are demonstrations of peoples knowing, tacit knowledge and therefore renewing of an organization.

Prediction of the economic cost of individual long-term care in the Spanish population

Pensions together with savings and investments during active life are key elements of retirement planning. Motivation for personal choices about the standard of living, bequest and the replacement ratio of pension with respect to last salary income must be considered. This research contributes to the financial planning by helping to quantify long-term care economic needs. We estimate life expectancy from retirement age onwards. The economic cost of care per unit of service is linked to the expected time of needed care and the intensity of required services. The expected individual cost of long-term care from an onset of dependence is estimated separately for men and women. Assumptions on the mortality of the dependent people compared to the general population are introduced. Parameters defining eligibility for various forms of coverage by the universal public social care of the welfare system are addressed. The impact of the intensity of social services on individual predictions is assessed, and a partial coverage by standard private insurance products is also explored. Data were collected by the Spanish Institute of Statistics in two surveys conducted on the general Spanish population in 1999 and in 2008. Official mortality records and life table trends were used to create realistic scenarios for longevity. We find empirical evidence that the public long-term care system in Spain effectively mitigates the risk of incurring huge lifetime costs. We also find that the most vulnerable categories are citizens with moderate disabilities that do not qualify to obtain public social care support. In the Spanish case, the trends between 1999 and 2008 need to be further explored.

Intensidad de cuidados enfermeros: ¿cargas de trabajo o complejidad individual?

Objetivo: explorar la identificación de los factores individuales de complejidad de cuidados en enfermos hospitalizados. Método: se empleó un diseño cualitativo de investigación-acción participativa con el método de análisis directo de contenido de los breves relatos de los participantes, enfermeras y enfermeros de los hospitales del lnstituto Catalán de la Salud, sobre casos en los que hubieran experimentado situaciones de complejidad. La suficiencia muestral se estableció a partir del criterio de saturación de la información. Los participantes fueron invitados a formar parte de una ronda de talleres/sesiones de discusión que se hicieron durante 18 meses. Uno de los investigadores recogía por escrito las opiniones de los participantes, mientras el otro moderaba el debate y realizaba preguntas reflexivas sobre el contenido de la propuesta. Posteriormente se invitaba a los participantes a organizarse en pequeños grupos para discutir y registrar en un fomulario individual, breves narrativas sobre casos en los que hubieran experimentado situaciones de complejidad. Resultados: el número de relatos breves incluidos en el análisis final fue de 287. Los factores individuales de complejidad de cuidados incluye cinco dominios: (1) evolutivo, (2) mental y cognitivo, (3) psicoemocional, (4) sociocultural y (5) comorbilidad y complicaciones. La complejidad individual de cuidados se estructura fuentes, factores y especificaciones. Conclusiones: de los cinco ejes de complejidad identificados en el Modelo Vectorial de Complejidad de Safford, cuatro coinciden parcialmente con el análisis presentado. La arquitectura de la complejidad de cuidados debería incluir una consideración multiperspectiva, incluyendo los ejes de complejidad individual, terapéutica-procedimental y organizativa.

Intensidad de cuidados enfermeros: ¿cargas de trabajo o complejidad individual?

Objetivo: explorar la identificación de los factores individuales de complejidad de cuidados en enfermos hospitalizados. Método: se empleó un diseño cualitativo de investigación-acción participativa con el método de análisis directo de contenido de los breves relatos de los participantes, enfermeras y enfermeros de los hospitales del lnstituto Catalán de la Salud, sobre casos en los que hubieran experimentado situaciones de complejidad. La suficiencia muestral se estableció a partir del criterio de saturación de la información. Los participantes fueron invitados a formar parte de una ronda de talleres/sesiones de discusión que se hicieron durante 18 meses. Uno de los investigadores recogía por escrito las opiniones de los participantes, mientras el otro moderaba el debate y realizaba preguntas reflexivas sobre el contenido de la propuesta. Posteriormente se invitaba a los participantes a organizarse en pequeños grupos para discutir y registrar en un fomulario individual, breves narrativas sobre casos en los que hubieran experimentado situaciones de complejidad. Resultados: el número de relatos breves incluidos en el análisis final fue de 287. Los factores individuales de complejidad de cuidados incluye cinco dominios: (1) evolutivo, (2) mental y cognitivo, (3) psicoemocional, (4) sociocultural y (5) comorbilidad y complicaciones. La complejidad individual de cuidados se estructura fuentes, factores y especificaciones. Conclusiones: de los cinco ejes de complejidad identificados en el Modelo Vectorial de Complejidad de Safford, cuatro coinciden parcialmente con el análisis presentado. La arquitectura de la complejidad de cuidados debería incluir una consideración multiperspectiva, incluyendo los ejes de complejidad individual, terapéutica-procedimental y organizativa.

Individual differences in gene expression : insights from transcriptional control of the CSL gene and from human population studies

CSL is a key transcription factor, mostly acting as a repressor, which has been shown to have a highly context-dependent function. While known as the main effector of Notch signaling, it can also exert Notch-independent functions. The downstream effects of the Notch/CSL signaling pathway and its involvement in several biological processes have been intensively studied. We recently showed that CSL is important to maintain skin homeostasis, as its specific deletion in mouse dermal fibroblasts -or downmodulation in human stromal fibroblasts- creates an inducing environment for squamous cell carcinoma (SCC) development, possibly due to the conversion of stromal fibroblasts into cancer associated fibroblasts (CAFs). Despite the wide interest in CSL as a transcriptional regulator, the mechanism of its own regulation has so far been neglected. We show here that CSL expression levels differ between individuals, and correlate among others with genes involved in DNA damage response. Starting from this finding we show that in dermal fibroblasts CSL is under transcriptional control of stress inducers such as UVA irradiation and Reactive Oxygen Species (ROS) induction, and that a main player in CSL transcriptional regulation is the transcription factor p53. In a separate line of work, we focused on individual variability, studying the differences in gene expression between human populations in various cancer types, particularly focusing on the Caucasian and African populations. It is indeed widely known that these populations have different incidences and mortalities for various cancers, and response to cancer treatment may also vary between them. We show here several genes that are differentially expressed and could be of interest in the study of population differences in cancer. -- CSL est un facteur de transcription agissant essentiellement comme répresseur, et qui a une fonction hautement dépendant du contexte. C'est l'effecteur principal de la voie de signalisation de Notch, mais il peut également exercer ses fonctions dans une façon Notch- indépendante. Nous avons récemment montré que CSL est important pour maintenir l'homéostasie de la peau. Sa suppression spécifique dans les fibroblastes dermiques de la souris ou dans les fibroblastes stromales humaines crée un environnement favorable pour le développement du carcinome épidermoïde (SCC), probablement en raison de la conversion des fibroblastes en fibroblastes associé au cancer (CAF). Malgré le grand intérêt de CSL comme régulateur transcriptionnel, le mécanisme de sa propre régulation a été jusqu'ici négligée. Nous montrons ici que dans les fibroblastes dermiques CSL est sous le contrôle transcriptionnel de facteurs de stress tels que l'irradiation UVA et l'induction des ROS dont p53 est l'acteur principal de cette régulation. Nous montrons aussi que les niveaux d'expression de CSL varient selon les individus, en corrélation avec d'autres gènes impliqués dans la réponse aux dommages de l'ADN. Dans une autre axe de recherche, concernant la variabilité individuelle, nous avons étudié les différences dans l'expression des gènes dans différents types de cancer entre les populations humaines, en se concentrant particulièrement sur les populations africaines et caucasiennes. Il est en effet bien connu que ces populations montrent des variations dans l'incidence des cancers, la mortalité, ainsi que pour les réponses au traitement. Nous montrons ici plusieurs gènes qui sont exprimés différemment et pourraient être digne d'intérêt dans l'étude du cancer au sein de différentes populations.

Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

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Peer-reviewed