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We recruit Psychological Value Theory (PVT) to understand how symptom value influences health-seeking decisions. Estimates of the Psychological Value of relief from a particular symptom were previously collected and used to predict the speed of participants' decision and the choice they make in three discrete choice experiments. Experiment 1 presented participants with a scenario and asked them to identify which of two symptoms they would seek healthcare services to treat. For each participant on every trial, two randomly chosen symptoms were inserted into the scenario. Experiment 2 addressed how the Psychological Value of a group of symptoms is predicted from the individual symptoms. Experiment 2 replicated Experiment 1 using groups of two symptoms, and predicted choice based on three grouping functions. Experiment 3 replicated Experiment 2 using a yes/no task, whereby participants were asked if they would pursue a health care visit for a single set of symptoms. The results showed that PVT accurately predicted speed and choice in all three experiments. The Psychological Value of relief from a symptom was the primary driver of choice along with a response bias in favor of avoiding symptoms labeled "severe."Health-seeking decisions are well modeled by a general-purpose, value-based computational model (PVT), with the Psychological Value of relief from health symptoms as a primary driver of health-seeking behavior.
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BACKGROUND: Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g. positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e. levels of antibodies), quantitative laboratory test data are needed. METHOD: 36 data attributes were collected from 3 NHS laboratories and 29 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports. RESULTS: A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems. CONCLUSIONS: This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/inmunología , COVID-19/epidemiología , COVID-19/sangre , Reino Unido/epidemiología , Prueba Serológica para COVID-19/normas , Prueba Serológica para COVID-19/métodos , Laboratorios/normas , Pandemias , Anticuerpos Antivirales/sangreRESUMEN
Introduction: The Minimum Information About BIobank Data Sharing (MIABIS) is a biobank-specific terminology enabling the sharing of biobank-related data for different purposes across a wide range of database implementations. After 4 years in use and with the first version of the individual-level MIABIS component Sample, Sample donor, and Event, it was necessary to revise the terminology, especially to include biobanks that work more in the data domain than with samples. Materials & Methods: Nine use-cases representing different types of biobanks, studies, and networks participated in the development work. They represent types of data, specific sample types, or levels of organization that were not included earlier in MIABIS. To support our revision of the Biobank entity, we conducted a survey of European biobanks to chart the services they provide. An important stakeholder group for biobanks include researchers as the main users of biobanks. To be able to render MIABIS more researcher-friendly, we collected different sample/data requests to analyze the terminology adjustment needs in detail. During the update process, the Core terminology was iteratively reviewed by a large group of experts until a consensus was reached. Results: With this update, MIABIS was adjusted to encompass data-driven biobanks and to include data collections, while also describing the services and capabilities biobanks offer to their users, besides the retrospective samples. The terminology was also extended to accommodate sample and data collections of nonhuman origin. Additionally, a set of organizational attributes was compiled to describe networks. Discussion: The usability of MIABIS Core v3 was increased by extending it to cover more topics of the biobanking domain. Additionally, the focus was on a more general terminology and harmonization of attributes with the individual-level entities Sample, Sample donor, and Event to keep the overall terminology minimal. With this work, the internal semantics of the MIABIS terminology was improved.
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Bancos de Muestras Biológicas , Difusión de la Información , Terminología como Asunto , Bancos de Muestras Biológicas/normas , Humanos , Bases de Datos FactualesRESUMEN
Strawboard has been utilised as a fragmentation capture material since the 1960s, mainly employed to capture fragments from explosives and explosive devices from arena trials of munitions. As this material has historically been calibrated to a known standard, it has a proven record of allowing research establishments to ascertain the velocity of a fragment based on the depth of penetration of the strawboard. During the time of calibration, strawboard was used as a common building material which was both widely available and relatively affordable; however, due to the recent economic crisis and geopolitical supply issues, this is no longer the case. Building on initial testing, this paper investigates alternatives to strawboard to determine if a cheaper, more readily available material can be used instead. The alternatives are compared and judged based on the NATO ARSP-03 guideline for capture material which includes metrics such as price and attainability, as well as assessing environmental impact and its ability to be used as a viable alternative to strawboard in an explosive environment. Based on these NATO guidelines, explosive fragmentation and ballistic experiments were conducted, and ten materials were tested based on the following criteria: Handling, Density, Flammability, Calibration, Cost and Availability. Medium Density Fibreboard (MDF) was found to be a suitable alternative to strawboard. The data demonstrates that it provides the same capture performance as strawboard at approximately a quarter of the cost and is far more readily available. Other materials also showed potential and further testing should be undertaken to validate these materials as alternatives to MDF.
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Charitable giving involves a complex economic and social decision because the giver expends resources for goods or services they will never receive. Although psychologists have identified numerous factors that influence charitable giving, there currently exists no unifying computational model of charitable choice. Here, we submit one such model, based within the strictures of Psychological Value Theory (PVT). In four experiments, we assess whether charitable giving is driven by the perceived Psychological Value of the recipient. Across all four experiments, we simultaneously predict response choice and response time with high accuracy. In a fifth experiment, we show that PVT predicts charitable giving more accurately than an account based on competence and warmth. PVT accurately predicts which charity a respondent will choose to donate to and separately, whether a respondent will choose to donate at all. PVT models the cognitive processes underlying charitable donations and it provides a computational framework for integrating known influences on charitable giving. For example, we show that in-group preference influences charitable giving by changing the Psychological Values of the options, rather than by bringing about a response bias toward the in-group.
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Cognición , Teoría Psicológica , Humanos , Tiempo de ReacciónRESUMEN
In serial reconstruction of order tasks, high-frequency words are better remembered than otherwise equivalent low-frequency words. Neath and Quinlan (2021) found that although the usual high-frequency advantage was observed when subjects received a block of low-frequency lists first followed by a block of high-frequency lists, there was no frequency effect when subjects received a block of high-frequency lists followed by a block of low-frequency lists. In order to assess whether the block order effect simply reflects the inherent changeability of frequency effects, we manipulated concreteness, a much more stable effect. Experiment 1 found a block order effect with concreteness: The usual advantage for concrete over abstract words was observed only when the abstract block came first and the concrete block second; when the block order was reversed, no concreteness effect was seen. In Experiment 2, subjects did not know whether the test would be serial reconstruction of order or immediate serial recall until after list presentation. This eliminated the block order effect, just as when frequency was manipulated. Experiment 3 found a block order effect with a free reconstruction of order task and with both open and closed stimulus sets. Given that the pattern of results with concreteness is the same as with frequency, it suggests the block order effect is not unique to frequency and that a more general explanation, such as a metacognitive account, is needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Recuerdo Mental , Metacognición , Humanos , Memoria a Corto PlazoRESUMEN
This paper presents the results of a study that used a speeded counting task to adjudicate between two competing theories of how perceptual representations of visual objects are derived. Boolean map (BM) theory assumes that there are strict limits on conscious awareness, such that we only have serial access to features on the same dimension (e.g., red and green). This theory contrasts with views that emphasize the early grouping of features, and which assume that feature processing is interactive and underpins figure/ground segregation as a necessary precursor to object perception. To test between these theories, we report performance in a speeded counting task in which participants were asked to judge which of two shapes was more prevalent. Displays contained squares and circles that appeared in either of two colors, with color and shape distinctions either perfectly correlated (i.e., compatible) or not (i.e., incompatible). BM theory predicts no influence of the relative coincidence of color and shape on the identification of the more prevalent shape. In contrast, grouping theory predicts that performance will be better when the color/shape distinction is compatible than when it is incompatible. Our data strongly support the grouping theory predictions. We conclude that the primary constraints on how visual objects are accessed are the number and kind of groupings that are recovered, not the number of feature maps consulted.
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BACKGROUND: The National Early Warning Score-2 (NEWS-2) is used to detect patient deterioration in UK hospitals but fails to take account of the detailed granularity or temporal trends in clinical observations. We used data-driven methods to develop dynamic early warning scores (DEWS) to address these deficiencies, and tested their accuracy in patients with respiratory disease for predicting (1) death or intensive care unit admission, occurring within 24 h (D/ICU), and (2) clinically significant deterioration requiring urgent intervention, occurring within 4 h (CSD). METHODS: Clinical observations data were extracted from electronic records for 31,590 respiratory in-patient episodes from April 2015 to December 2020 at a large acute NHS Trust. The timing of D/ICU was extracted for all episodes. 1100 in-patient episodes were annotated manually to record the timing of CSD, defined as a specific event requiring a change in treatment. Time series features were entered into logistic regression models to derive DEWS for each of the clinical outcomes. Area under the receiver operating characteristic curve (AUROC) was the primary measure of model accuracy. RESULTS: AUROC (95% confidence interval) for predicting D/ICU was 0.857 (0.852-0.862) for NEWS-2 and 0.906 (0.899-0.914) for DEWS in the validation data. AUROC for predicting CSD was 0.829 (0.817-0.842) for NEWS-2 and 0.877 (0.862-0.892) for DEWS. NEWS-2 ≥ 5 had sensitivity of 88.2% and specificity of 54.2% for predicting CSD, while DEWS ≥ 0.021 had higher sensitivity of 93.6% and approximately the same specificity of 54.3% for the same outcome. Using these cut-offs, 315 out of 347 (90.8%) CSD events were detected by both NEWS-2 and DEWS, at the time of the event or within the previous 4 h; 12 (3.5%) were detected by DEWS but not by NEWS-2, while 4 (1.2%) were detected by NEWS-2 but not by DEWS; 16 (4.6%) were not detected by either scoring system. CONCLUSION: We have developed DEWS that display greater accuracy than NEWS-2 for predicting clinical deterioration events in patients with respiratory disease. Prospective validation studies are required to assess whether DEWS can be used to reduce missed deteriorations and false alarms in real-life clinical settings.
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Deterioro Clínico , Puntuación de Alerta Temprana , Trastornos Respiratorios , Enfermedades Respiratorias , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Curva ROC , Estudios RetrospectivosRESUMEN
OBJECTIVE: Annotated clinical samples taken from patients are a foundation of translational medical research and give mechanistic insight into drug trials. Prior research by the Tissue Directory and Coordination Centre (TDCC) indicated that researchers, particularly those in industry, face many barriers in accessing patient samples. The arrival of the COVID-19 pandemic to the UK produced an immediate and extreme shockwave, which impacted on the ability to undertake all crucial translational research. As a national coordination centre, the TDCC is tasked with improving efficiency in the biobanking sector. Thus, we took responsibility to identify and coordinate UK tissue sample collection organisations (biobanks) able to collect COVID-19-related samples for researchers between March and September 2020. FINDINGS: Almost a third of UK biobanks were closed during the first wave of the UK COVID-19 pandemic. Of the remainder, 43% had limited capabilities while 26% maintained normal activity. Of the nationally prioritised COVID-19 interventional studies, just three of the five that responded to questioning were collecting human samples. Of the 41 requests for COVID-19 samples received by the TDCC, only four could be fulfilled due to a lack of UK coordinated strategy. Meanwhile, in the background there are numerous reports that sample collections in the UK remain largely underutilised. CONCLUSION: The response to a pandemic demands high level co-ordinated research responses to reduce mortality. Our study highlights the lack of efficiency and coordination between human sample collections and clinical trials across the UK. UK sample access is not working for researchers, clinicians or patients. A radical change is required in the strategy for sample collection and distribution to maximise this valuable resource of human-donated samples.
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COVID-19 , Bancos de Muestras Biológicas , COVID-19/epidemiología , Humanos , Pandemias , Reino Unido/epidemiologíaRESUMEN
Various biological resources, such as biobanks and disease-specific registries, have become indispensable resources to better understand the epidemiology and biological mechanisms of disease and are fundamental for advancing medical research. Nevertheless, biobanks and similar resources still face significant challenges to become more findable and accessible by users on both national and global scales. One of the main challenges for users is to find relevant resources using cataloging and search services such as the BBMRI-ERIC Directory, operated by European Research Infrastructure on Biobanking and Biomolecular Resources (BBMRI-ERIC), as these often do not contain the information needed by the researchers to decide if the resource has relevant material/data; these resources are only weakly characterized. Hence, the researcher is typically left with too many resources to explore and investigate. In addition, resources often have complex procedures for accessing holdings, particularly for depletable biological materials. This article focuses on designing a system for effective negotiation of access to holdings, in which a researcher can approach many resources simultaneously, while giving each resource team the ability to implement their own mechanisms to check if the material/data are available and to decide if access should be provided. The BBMRI-ERIC has developed and implemented an access and negotiation tool called the BBMRI-ERIC Negotiator. The Negotiator enables access negotiation to more than 600 biobanks from the BBMRI-ERIC Directory and other discovery services such as GBA/BBMRI-ERIC Locator or RD-Connect Finder. This article summarizes the principles that guided the design of the tool, the terminology used and underlying data model, request workflows, authentication and authorization mechanism(s), and the mechanisms and monitoring processes to stimulate the desired behavior of the resources: to effectively deliver access to biological material and data.
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Bancos de Muestras Biológicas , Investigación Biomédica , Difusión de la InformaciónRESUMEN
According to the item/order hypothesis, high-frequency words are processed more efficiently and therefore order information can be readily encoded. In contrast, low-frequency words are processed less efficiently and the focus on item-specific processing compromises order information. Most experiments testing this account use free recall, which has led to two problems: First, the role of order information is difficult to evaluate in free recall, and second, the data from free recall show all three possible patterns of results: memory for high-frequency words can be better than, the same as, or worse than that for low-frequency words. A series of experiments tested the item/order hypothesis using tests where the role of order information is less ambiguous. The item/order hypothesis predicts better performance for high- than low-frequency words when pure lists are used in both immediate serial recall (ISR) and serial reconstruction of order (SRO) tests. In contrast, when mixed (alternating) lists are used, it predicts better performance for low- than for high-frequency words with ISR tests, but equivalent performance with SRO tests. The experiments generally confirm these predictions, with the notable exception of a block order effect in SRO tasks: When a block of low-frequency lists preceded a block of high-frequency lists, a high-frequency advantage was observed but when a block of high-frequency lists preceded a block of low-frequency lists, no frequency effect was observed. A final experiment provides evidence that this block order effect is due to metacognitive factors.
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Metacognición , Aprendizaje Seriado , Humanos , Memoria a Corto Plazo , Recuerdo MentalRESUMEN
Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.
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Neoplasias de la Mama , Proteínas de Choque Térmico Pequeñas , Proteínas de Choque Térmico/metabolismo , Chaperonas Moleculares/metabolismo , Neoplasias de la Mama/genética , Análisis por Conglomerados , Femenino , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico/análisis , Humanos , Chaperonas Moleculares/análisis , Cadena B de alfa-Cristalina/metabolismoRESUMEN
The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing a mouse-human cross species analysis between the TAp63 metastatic mammary adenocarcinoma mouse model and models of human breast cancer progression, we identified two TAp63-regulated oncogenic lncRNAs, TROLL-2 and TROLL-3. Further, using a pan-cancer analysis of human cancers and multiple mouse models of tumour progression, we revealed that these two lncRNAs induce the activation of AKT to promote cancer progression by regulating the nuclear to cytoplasmic translocation of their effector, WDR26, via the shuttling protein NOLC1. Our data provide preclinical rationale for the implementation of these lncRNAs and WDR26 as therapeutic targets for the treatment of human tumours dependent upon mutant TP53 and/or the PI3K/AKT pathway.
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Adenocarcinoma/genética , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Mamarias Experimentales/genética , ARN Largo no Codificante/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/patología , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Humanos , Glándulas Mamarias Animales/citología , Neoplasias Mamarias Experimentales/patología , Ratones , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Cultivo Primario de Células , Proteínas Proto-Oncogénicas c-akt/metabolismo , RNA-Seq , Transducción de Señal/genética , Análisis de Matrices Tisulares , Transactivadores/genética , Factores de Transcripción/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Here we report the results of a speeded relative quantity task with Chinese participants. On each trial a single numeral (the probe) was presented and the instructions were to respond as to whether it signified a quantity less than or greater than five (the standard). In separate blocks of trials, the numerals were presented either in Mandarin or in Arabic number formats. In addition to the standard influence of numerical distance, a significant predictor of performance was the degree of physical similarity between the probe and the standard as depicted in Mandarin. Additionally, competing effects of physical similarity, defined in terms of the Arabic number format, were also found. Critically the size of these different effects of physical similarity varied systematically across individuals such that larger effects of one compensated for smaller effects of the other. It is argued that the data favor accounts of processing that assume that different number formats access different format-specific representations of quantities. Moreover, for Chinese participants the default is to translate numerals into a Mandarin format prior to accessing quantity information. The efficacy of this translation process is itself influenced by a competing tendency to carry out a translation into Arabic format.
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Solución de Problemas , China , HumanosRESUMEN
Introduction: The use of human-derived samples is vital to numerous areas of biological and medical research. Despite this, researchers often find or anticipate difficulty in sourcing samples. There are ongoing efforts to increase the visibility and accessibility of UK human tissue biobanking, but minimal (if any) research on the reasons behind researchers' choice of sample source has been undertaken. We have analyzed UK researchers' motivations on using their preferred sample sources and their perceived barriers to human sample use. Methods: The study was based on an online survey of academic and industry researchers, followed by focus groups, with participants across the United Kingdom. Both the survey and focus groups probed participants' views on the barriers to finding and using human samples in research. Results: One hundred ninety-eight academic and industry researchers completed the survey on their human sample use, and five focus groups consisting of 21 total participants took place. The top cited reasons for choosing sources included the availability of linked clinical data (40%), the geographical location of the resource (39%), and preexisting collaboration (33%). Focus group participants highlighted their strong preference for local or known sample sources, which were preferred because additional scientific and logistical input could be obtained for their work and they were more confident that the samples would be of good quality. Discussion: We found that there were significant perceptions of governance barriers to sample access. As a consequence, researchers preferred local and known suppliers because of the perception that these could assist with the governance, would be reliable, and able to provide the additional support they required. Equally, data availability was a major contributor to the selection of a new source of samples. These observations are of significant value to those seeking to improve the access to existing sample resources via online discovery tools.
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Bancos de Muestras Biológicas , Motivación , Investigadores/psicología , Investigación Biomédica , Confidencialidad , Grupos Focales , Humanos , Encuestas y Cuestionarios , Reino UnidoRESUMEN
INTRODUCTION: Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission. METHODS AND ANALYSIS: A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data. ETHICS AND DISSEMINATION: The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results].
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Cuidados Posteriores , Unidades de Cuidado Intensivo Pediátrico , Calidad de Vida , Niño , Cuidados Críticos , Humanos , Estudios Longitudinales , Estudios Multicéntricos como Asunto , Alta del PacienteRESUMEN
Introduction: The Minimum Information About BIobank data Sharing (MIABIS) was initiated in 2012. MIABIS aims to create a common biobank terminology to facilitate data sharing in biobanks and sample collections. The MIABIS Core terminology consists of three components describing biobanks, sample collections, and studies, in which information on samples and sample donors is provided at aggregated form. However, there is also a need to describe samples and sample donors at an individual level to allow more elaborate queries on available biobank samples and data. Therefore the MIABIS terminology has now been extended with components describing samples and sample donors at an individual level. Materials and Methods: The components were defined according to specific scope and use cases by a large group of experts, and through several cycles of reviews, according to the new MIABIS governance model of BBMRI-ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium). The guiding principles applied in developing these components included the following terms: model should consider only samples of human origin, model should be applicable to all types of samples and all sample donors, and model should describe the current status of samples stored in a given biobank. Results: A minimal set of standard attributes for defining samples and sample donors is presented here. We added an "event" component to describe attributes that are not directly describing samples or sample donors but are tightly related to them. To better utilize the generic data model, we suggest a procedure by which interoperability can be promoted, using specific MIABIS profiles. Discussion: The MIABIS sample and donor component extensions and the new generic data model complement the existing MIABIS Core 2.0 components, and substantially increase the potential usability of this terminology for better describing biobank samples and sample donors. They also support the use of individual level data about samples and sample donors to obtain accurate and detailed biobank availability queries.
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Bancos de Muestras Biológicas , Difusión de la Información/métodos , Guías como Asunto , Humanos , Terminología como AsuntoRESUMEN
ΔNp63, also known as p40, regulates stemness of normal mammary gland epithelium and provides stem cell characteristics in basal and HER2-driven murine breast cancer models. Whilst ΔNp63/p40 is a characteristic feature of normal basal cells and basal-type triple-negative breast cancer, some receptor-positive breast cancers express ΔNp63/p40 and its overexpression imparts cancer stem cell-like properties in ER+ cell lines. However, the incidence of ER+ and HER2+ tumours that express ΔNp63/p40 is unclear and the phenotype of ΔNp63/p40+ cells in these tumours remains uncertain. Using immunohistochemistry with p63 isoform-specific antibodies, we identified a ΔNp63/p40+ tumour cell subpopulation in 100 of 173 (58%) non-triple negative breast cancers and the presence of this population associated with improved survival in patients with ER- /HER2+ tumours (p = 0.006). Furthermore, 41% of ER+ /PR+ and/or HER2+ locally metastatic breast cancers expressed ΔNp63/p40, and these cells commonly accounted for <1% of the metastatic tumour cell population that localised to the tumour/stroma interface, exhibited an undifferentiated phenotype and were CD44+ /ALDH- . In vitro studies revealed that MCF7 and T47D (ER+ ) and BT-474 (HER2+ ) breast cancer cell lines similarly contained a small subpopulation of ΔNp63/p40+ cells that increased in mammospheres. In vivo, MCF7 xenografts contained ΔNp63/p40+ cells with a similar phenotype to primary ER+ cancers. Consistent with tumour samples, these cells also showed a distinct location at the tumour/stroma interface, suggesting a role for paracrine factors in the induction or maintenance of ΔNp63/p40. Thus, ΔNp63/p40 is commonly present in a small population of tumour cells with a distinct phenotype and location in ER+ and/or HER2+ human breast cancers.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Células Madre Neoplásicas/patología , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Xenoinjertos , Humanos , Ratones , Células Madre Neoplásicas/metabolismo , Fenotipo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismoRESUMEN
The architecture of the numerical cognition system is currently not well understood, but at a general level, assumptions are made about two core components: a quantity processor and an identity processor. The quantity processor is concerned with accessing and using the stored magnitude denoted by a given digit, and the identity processor is concerned with recovery of the corresponding digit's identity. Blanc-Goldhammer and Cohen (Journal of Experimental Psychology: Learning, Memory, and Cognition, 40, 1389-1403, 2014) established that the recovery and use of quantity information operates in an unlimited-capacity fashion. Here we assessed whether the identity processor operates in a similar fashion. We present two experiments that were digit identity variations of Blanc-Goldhammer and Cohen's magnitude estimation paradigm. The data across both experiments reveal a limited-capacity identity processor whose operation reflects cross-talk with the quantity processor. Such findings provide useful evidence that can be used to adjudicate between competing models of the human number-processing system.