RESUMEN
To study linguistically coded concepts, researchers often resort to the Property Listing Task (PLT). In a PLT, participants are asked to list properties that describe a concept (e.g., for DOG, subjects may list "is a pet", "has four legs", etc.). When PLT data is collected for many concepts, researchers obtain Conceptual Properties Norms (CPNs), which are used to study semantic content and as a source of control variables. Though the PLT and CPNs are widely used across psychology, only recently a model that describes the listing course of a PLT has been developed and validated. That original model describes the listing course using order of production of properties. Here we go a step beyond and validate the model using response times (RT), i.e., the time from cue onset to property listing. Our results show that RT data exhibits the same regularities observed in the previous model, but now we can also analyze the time course, i.e., dynamics of the PLT. As such, the RT validated model may be applied to study several similar memory retrieval tasks, such as the Free Listing Task, Verbal Fluidity Task, and to research related cognitive processes. To illustrate those kinds of analyses, we present a brief example of the difference in PLT's dynamics between listing properties for abstract versus concrete concepts, which shows that the model may be fruitfully applied to study concepts.
Asunto(s)
Memoria , Semántica , Humanos , Tiempo de ReacciónRESUMEN
In this paper, we present a novel algorithm that uses machine learning and natural language processing techniques to facilitate the coding of feature listing data. Feature listing is a method in which participants are asked to provide a list of features that are typically true of a given concept or word. This method is commonly used in research studies to gain insights into people's understanding of various concepts. The standard procedure for extracting meaning from feature listings is to manually code the data, which can be time-consuming and prone to errors, leading to reliability concerns. Our algorithm aims at addressing these challenges by automatically assigning human-created codes to feature listing data that achieve a quantitatively good agreement with human coders. Our preliminary results suggest that our algorithm has the potential to improve the efficiency and accuracy of content analysis of feature listing data. Additionally, this tool is an important step toward developing a fully automated coding algorithm, which we are currently preliminarily devising.
RESUMEN
Introduction: The response to vaccination against the virus that causes severe acute respiratory infection syndrome coronavirus 2 is lower in renal transplant recipients than in the general population. The data obtained from Latin America showed reduced immunogenicity under inactivated virus vaccination schedules and messenger ribonucleic acid platforms. Methods: A retrospective cohort study including renal transplant recipients from Colombia with a two-dose vaccination schedule against severe acute respiratory infection syndrome coronavirus 2 with Pfizer, AstraZeneca, Moderna, Jansen, and Sinovac vaccines between March 1, 2021 and December 1, 2021, was carried out with a follow-up period to evaluate outcomes until May 2022. The outcomes correspond to the titers of immunoglobulin G antibodies against the receptor binding domain of the severe acute respiratory infection syndrome coronavirus 2 spike and a composite outcome of mortality, general, and intensive care unit hospitalization. Results: In total, 215 renal transplant recipients with two doses of vaccination for severe acute respiratory infection syndrome coronavirus 2 during the predominance of the Omicron variant in Colombia were included, with the measurement of immunoglobulin G antibody titers against the receptor binding domain of the severe acute respiratory infection syndrome coronavirus 2 spike at 8 weeks of vaccination. The mean age was 52.1 years, and the standard deviation was ± 14.2; severe acute respiratory infection syndrome coronavirus 2 infection occurred in 20% of the population, of which 23.26% required hospitalization, 13.95% were under intensive care unit management, and four cases of mortality (9.3%) were reported. Of the total population, 52.5% had antibody titers higher than 0.8 IU/mL (median 0.77 IU/mL, interquartile range 0.4-131). Patients with severe acute respiratory infection syndrome coronavirus 2 infection had a median antibody titer of 0.4 IU/mL (interquartile range 0.4-3.45), and those without infection had a median antibody titer of 1.8 IU/mL (interquartile range 0.4-202) (p = 0.015). Conclusion: Anti-severe acute respiratory infection syndrome coronavirus 2 antibody titers with a cutoff point less than 0.8 IU/mL are associated with increased risk of severe acute respiratory infection syndrome coronavirus 2 infection.
RESUMEN
The aim of this study was to investigate the transfer of residues of five ß-lactam antibiotics (ampicillin, penicillin G, cloxacillin, dicloxacillin and cephalexin) and two tetracyclines (tetracycline and oxytetracycline) in the processing of cheese and whey powder, evaluating the effect of the processes and the final concentration in each product generated. Raw milk was fortified at two concentration levels with the seven antibiotics. The first concentration level (C1) was chosen according to the maximum residue limit (MRL) of each antibiotic (ampicillin and penicillin G: 4 µg kg-1; cloxacillin and dicloxacillin: 30 µg kg-1; cephalexin, tetracycline and oxytetracycline: 100 µg kg-1). The second concentration level (C2) was spiked as follows according to each antibiotic: 0.5 MRL (cloxacillin, dicloxacillin, cephalexin), 0.1 MRL (tetracycline and oxytetracycline) and 3 MRL (ampicillin and penicillin G). The antibiotics were analyzed by LC-MS/MS. No ampicillin or penicillin G residues were found in cheese or whey powder, although they were detected in whey at concentrations similar to those added to raw milk. Cephalexin was mostly distributed in whey between 82% and 96%, being the antibiotic that presented the highest concentration in whey powder (784 ± 98 µg kg-1) when milk was spiked at the MRL. The whey distribution of cloxacillin and dicloxacillin ranged from 57% to 59% for cloxacillin and from 46% to 48% for dicloxacillin, and both concentrated in whey powder. Tetracyclines were the antibiotics that concentrated in cheese, with retentions between 75% and 80% for oxytetracycline and between 83% and 87% for tetracycline. The distribution of antibiotics in the dissimilar stages of the cheese and whey powder production processes, as well as their concentration in the final products, depend on each type of antibiotic. Knowledge of the transfer of antibiotic residues during the process and final disposal is an input for the risk assessment of their consumption.
Asunto(s)
Queso , Residuos de Medicamentos , Oxitetraciclina , Animales , Leche/química , beta-Lactamas/análisis , Tetraciclina/análisis , Polvos/análisis , Queso/análisis , Oxitetraciclina/análisis , Suero Lácteo/química , Dicloxacilina/análisis , Cromatografía Liquida , Espectrometría de Masas en Tándem , Antibacterianos/análisis , Tetraciclinas/análisis , Cloxacilina , Ampicilina , Cefalexina , Residuos de Medicamentos/análisisRESUMEN
La menopausia provoca cambios hormonales y alteraciones sistémicas. La menopausia normal sucede entre los 45-55 años y la menopausia temprana (MT) se desarrolla antes de los 45 años. Revisar la evidencia que señala posibles asociaciones entre la MT y la función pulmonar, analizando específicamente aquellos componentes que se encuentran alterados. Se eligieron estudios transversales y revisiones sistemáticas, en inglés, portugués y español. La búsqueda se realizó de marzo a noviembre de2022, en PubMed y Scopus, aemás de búsquedas manuales. La calidad metodológica fue analizada utilizando la escala Strengthening the Reporting of Observational Studies in Epidemiology para los estudios observacionales, y el Ameasurement Tool to Assess Systematic Review para las revisiones. Se encontraron 698 estudios, 12 seleccionados para calificación metodológica, cinco excluidos. Al final del análisis metodológico, se obtuvieron seis estudios transversales y una revisión sistemática, llevados a cabo en Reino Unido, Europa y Asia. Hay una tendencia para asociación de la MT a un patrón ventilatorio restrictivo. Sin embargo la evidencia sigue siendo escasa y se sugiere la realización de nuevos estudios.
Menopause causes hormonal changes and systemic alterations. Normal menopause is when this event occurs between the ages of 45 and 55, and early menopause (EM) when it develops earlier than 45 years. To review the evidence that indicates possible associations between EM and lung function, specifically analyzing those components that are altered. Cross-sectional and systematic reviews studies, published from 2000-2022, in English, Portuguese and Spanish were selected from March to November 2022, in PubMed and Scopus and through manual searches. Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology scale for observational studies, and the Measurement Tool to Assess Systematic Review for reviews. 698 studies were found, 12 were selected for methodological quality review and 5 were excluded. At the end of methodological analysis, 6 cross-sectional studies and 1 systematic review were obtained, carried out in United Kingdom, Europe and Asia. There is a tendency for EM to be associated with restrictive ventilatory pattern. However, the evidence is scarce and further studies are suggested.
Asunto(s)
Humanos , Femenino , Menopausia Prematura , Pulmón/fisiología , EnvejecimientoRESUMEN
In conceptual properties norming studies (CPNs), participants list properties that describe a set of concepts. From CPNs, many different parameters are calculated, such as semantic richness. A generally overlooked issue is that those values are only point estimates of the true unknown population parameters. In the present work, we present an R package that allows us to treat those values as population parameter estimates. Relatedly, a general practice in CPNs is using an equal number of participants who list properties for each concept (i.e., standardizing sample size). As we illustrate through examples, this procedure has negative effects on data's statistical analyses. Here, we argue that a better method is to standardize coverage (i.e., the proportion of sampled properties to the total number of properties that describe a concept), such that a similar coverage is achieved across concepts. When standardizing coverage rather than sample size, it is more likely that the set of concepts in a CPN all exhibit a similar representativeness. Moreover, by computing coverage the researcher can decide whether the CPN reached a sufficiently high coverage, so that its results might be generalizable to other studies. The R package we make available in the current work allows one to compute coverage and to estimate the necessary number of participants to reach a target coverage. We show this sampling procedure by using the R package on real and simulated CPN data.
Asunto(s)
Proyectos de Investigación , Semántica , Humanos , Tamaño de la MuestraRESUMEN
Agreement probability p(a) is a homogeneity measure of lists of properties produced by participants in a Property Listing Task (PLT) for a concept. Agreement probability's mathematical properties allow a rich analysis of property-based descriptions. To illustrate, we use p(a) to delve into the differences between concrete and abstract concepts in sighted and blind populations. Results show that concrete concepts are more homogeneous within sighted and blind groups than abstract ones (i.e., exhibit a higher p(a) than abstract ones) and that concrete concepts in the blind group are less homogeneous than in the sighted sample. This supports the idea that listed properties for concrete concepts should be more similar across subjects due to the influence of visual/perceptual information on the learning process. In contrast, abstract concepts are learned based mainly on social and linguistic information, which exhibit more variability among people, thus, making the listed properties more dissimilar across subjects. Relative to abstract concepts, the difference in p(a) between sighted and blind is not statistically significant. Though this is a null result, and should be considered with care, it is expected because abstract concepts should be learned by paying attention to the same social and linguistic input in both, blind and sighted, and thus, there is no reason to expect that the respective lists of properties should differ. Finally, we used p(a) to classify concrete and abstract concepts with a good level of certainty. All these analyses suggest that p(a) can be fruitfully used to study data obtained in a PLT.
RESUMEN
AIMS: Sensor augmented insulin pumps have become a powerful tool for managing type 1 diabetes (T1D). This study aimed to analyze the insulin pump configuration in users of predictive insulin suspension technology (PLGS). METHODS: T1D patients on insulin pumps with PLGS (Medtronic 640G®) were enrolled. Data was obtained from medical records and pump data was downloaded for 30 days. Basal insulin, bolus calculator parameters, and PLGS operation parameters were analyzed and compared with Time in Range, Time Below Range, and Time Above Range. RESULTS: 112 patients were included, with average TIR of 73,96 % and HbA1c 7,0 % and 25 months of follow-up. Basal insulin remained similar to initial doses, with an increase of 27 % for the Dawn phenomenon. The Carbohydrate ratio was slightly more aggressive. Insulin sensitivity was 17 % less stringent than initially programmed. No differences were observed in Time in Rage according to the number of basal, ratio, and sensitivity segments. Time of insulin suspension correlated directly with Time Bellow Range. CONCLUSIONS: Patients with good metabolic control have basal insulin programming similar to their initiation doses with less aggressive sensitivity factors. Excessive suspension time determined by PLGS could be an expression of excess insulin and increased hypoglycemia risk.
Asunto(s)
Diabetes Mellitus Tipo 1 , Hiperinsulinismo , Glucemia , Chile/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Hiperinsulinismo/complicaciones , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Insulina Regular HumanaRESUMEN
To study concepts that are coded in language, researchers often collect lists of conceptual properties produced by human subjects. From these data, different measures can be computed. In particular, inter-concept similarity is an important variable used in experimental studies. Among possible similarity measures, the cosine of conceptual property frequency vectors seems to be a de facto standard. However, there is a lack of comparative studies that test the merit of different similarity measures when computed from property frequency data. The current work compares four different similarity measures (cosine, correlation, Euclidean and Chebyshev) and five different types of data structures. To that end, we compared the informational content (i.e., entropy) delivered by each of those 4 × 5 = 20 combinations, and used a clustering procedure as a concrete example of how informational content affects statistical analyses. Our results lead us to conclude that similarity measures computed from lower-dimensional data fare better than those calculated from higher-dimensional data, and suggest that researchers should be more aware of data sparseness and dimensionality, and their consequences for statistical analyses.
Asunto(s)
Algoritmos , Lenguaje , Análisis por Conglomerados , HumanosRESUMEN
Precise coordination of cell expansion and cell proliferation underlies growth in multicellular organisms. In addition to endogenous developmental programs, external environmental signals are integrated to modulate organ growth in plants. Nitrate is a nitrogen nutrient that can act as a potent signal to modulate shoot growth, yet the molecular mechanisms involved are largely unexplored in Arabidopsis thaliana or other plant species. Herein, we show that nitrate regulates vegetative growth by modulating cell size and endoreplication. We identified the LGO gene, a CDK inhibitor, as a key cell cycle regulatory factor influencing ploidy and cell-size depending on external nitrate. Nitrate induces LGO gene expression as early as 3 days after germination in epidermal and mesophyll cell layers, which undergo endoreplication to increment DNA content and cell size. Our results support a dual role for LGO on endoreplication and cell expansion. Surprisingly, although endoreplication and cell size are greatly reduced in lgo-2 mutant plants and increased in LGO-OX plants, cotyledon size remains unchanged relative to wild type and is set by the amount of nitrate. In lgo-2 mutant plants where cells are unable to endoreplicate fully, cotyledon organ size is achieved through cell division. We conclude nitrate generally controls cotyledon and leaf size by increasing ploidy levels and cell expansion but that cell division can substitute for endoreplication without affecting final organ size or growth in plants.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efectos de los fármacos , Arabidopsis/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Nitratos/farmacología , Proteínas Nucleares/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Reducción Gradual de Medicamentos , Regulación del Desarrollo de la Expresión Génica , Nitratos/administración & dosificación , Proteínas Nucleares/genética , Tallos de la Planta/efectos de los fármacos , Transducción de SeñalRESUMEN
RESUMEN Objetivo: Describir y discutir la evidencia actual sobre la relación entre desempeño cognitivo, trastorno afectivo bipolar (TAB) y síndrome metabólico (SM). Métodos: Se buscaron artículos relacionados en distintas bases de datos bibliográficas (MEDLINE, EMBASE, Scielo), y con los artículos seleccionados se realizó una revisión narrativa de la literatura. Resultados: Hasta el momento no se ha estudiado ampliamente el SM en el TAB, pero sí hay datos importantes en la asociación con las variables metabólicas individuales. Se señala que la obesidad de los pacientes con TAB se asocia con peor desempeño en memoria verbal, velocidad de procesamiento psicomotor y atención sostenida. Parecería que la hipertrigliceridemia de los pacientes con TAB está en relación con deterioro en la función ejecutiva, y la hipertensión arterial, con el deterioro en la función cognitiva general. Conclusiones: Aunque algunas variables del SM se asocian con peor desempeño cognitivo en pacientes con TAB, faltan estudios para establecer con precisión la naturaleza de esta relación.
ABSTRACT Objective: To describe and discuss current evidence on the relationship between cognitive performance, Bipolar Affective Disorder (BAD) and Metabolic Syndrome (MS). Methods: We searched for related articles in different bibliographic databases (MEDLINE, EMBASE, Scielo) and performed a narrative review of the literature with the selected articles. Results: To date, evidence has not been conclusive and the effect of MS on BD has not been widely studied, but important correlations have been observed with individual metabolic variables. It is suggested that obesity in patients with BAD is associated wotj worse performance in verbal memory, psychomotor processing speed, and sustained attention. Hypertriglyceridemia in patients with BAD appears to be associated with a lower score in executive function tasks; hypertension appears to be associated with impairment in overall cognitive function. Conclusions: Despite the associations between MS and poor cognitive performance in patients suffering from BAD, more studies are required to precisely determine how these variables are related to each other.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Trastorno Bipolar , Cognición , Síndrome Metabólico , Estrés Psicológico , Trastornos del Humor , MemoriaRESUMEN
OBJECTIVE: To describe and discuss current evidence on the relationship between cognitive performance, Bipolar Affective Disorder (BAD) and Metabolic Syndrome (MS). METHODS: We searched for related articles in different bibliographic databases (MEDLINE, EMBASE, Scielo) and performed a narrative review of the literature with the selected articles. RESULTS: To date, evidence has not been conclusive and the effect of MS on BD has not been widely studied, but important correlations have been observed with individual metabolic variables. It is suggested that obesity in patients with BAD is associated wotj worse performance in verbal memory, psychomotor processing speed, and sustained attention. Hypertriglyceridemia in patients with BAD appears to be associated with a lower score in executive function tasks; hypertension appears to be associated with impairment in overall cognitive function. CONCLUSIONS: Despite the associations between MS and poor cognitive performance in patients suffering from BAD, more studies are required to precisely determine how these variables are related to each other.
Asunto(s)
Trastorno Bipolar/psicología , Cognición , Síndrome Metabólico/psicología , Trastorno Bipolar/complicaciones , Humanos , Síndrome Metabólico/complicacionesRESUMEN
Coordination between plant development and nutrient availability ensures a suitable supply of macromolecules for growth and developmental programs. Nitrate is an important source of nitrogen (N) that acts as a signal molecule to modulate gene expression, physiological, growth and developmental responses throughout the life of the plant. New key players in the nitrate signaling pathway have been described and knowledge of the molecular mechanics of how it impacts growth and developmental processes is increasing fast. Importantly, mechanisms for nitrate-control of growth and developmental processes have been proposed for both local as well as systemic responses. This article provides a synthesis of recent insights into molecular mechanisms by which nitrate impacts growth and development over Arabidopsis life-cycle.
Asunto(s)
Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Nitratos/metabolismo , Transducción de Señal , Flores/fisiología , Germinación , Semillas/crecimiento & desarrolloRESUMEN
The reproductive success of plants largely depends on the correct programming of developmental phase transitions, particularly the shift from vegetative to reproductive growth. The timing of this transition is finely regulated by the integration of an array of environmental and endogenous factors. Nitrogen is the mineral macronutrient that plants require in the largest amount, and as such its availability greatly impacts on many aspects of plant growth and development, including flowering time. We found that nitrate signaling interacts with the age-related and gibberellic acid pathways to control flowering time in Arabidopsis thaliana. We revealed that repressors of flowering time belonging to the AP2-type transcription factor family including SCHLAFMUTZE (SMZ) and SCHNARCHZAPFEN (SNZ) are important regulators of flowering time in response to nitrate. Our results support a model whereby nitrate activates SMZ and SNZ via the gibberellin pathway to repress flowering time in Arabidopsis thaliana.
Asunto(s)
Proteínas de Arabidopsis/genética , Arabidopsis/fisiología , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Giberelinas/metabolismo , Nitratos/metabolismo , Factores de Transcripción/genética , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores/genética , Transducción de Señal , Factores de Transcripción/metabolismoRESUMEN
Resumen Introducción y objetivos: La apatía, entendida como un déficit para el inicio y el mantenimiento de la acción, es un síntoma que afecta a los pacientes con diversas enfermedades psiquiátricas y neuropsiquiátricas, como demencias, secuelas de traumatismo craneal, esquizofrenia y depresión y enfermedad de Parkinson (EP). La apatía afecta negativamente a la funcionalidad y la calidad de vida de los pacientes con EP y es fuente importante de estrés del cuidador. El tratamiento farmacológico de la apatía en la EP es el foco de esta revisión sistemática. Métodos: Se realizó una búsqueda con selección sistemática de artículos originales sobre el tratamiento de la apatía en la EP en diferentes bases de datos, se consolidaron los resultados, se realizó lectura crítica de los artículos y se discutieron los hallazgos. Resultados: Se incluyeron 11 estudios. Aunque algunos mostraron eficacia, todos presentaban limitaciones metodológicas importantes, que no permitían considerar que se pueda tomar en cuenta los resultados de dichos ensayos clínicos como evidencia para guiar las decisiones clínicas. Conclusiones: Hasta el momento no se puede ofrecer recomendaciones basadas en la evidencia para el tratamiento farmacológico de la apatía en la EP. Hacen falta estudios con mejor calidad metodológica. Es un área de investigación potencialmente fructífera y muy necesaria para los pacientes con EP y sus familiares.
Abstract Introduction and objectives: Apathy, defined as a deficit for initiating and maintaining action, is a symptom affecting patients with diverse psychiatric and neuropsychiatric diseases, including dementia, sequelae of traumatic brain injury, schizophrenia, depression, and Parkinson's disease (PD). Apathy negatively affects function and quality of life of PD patients, and it is an important cause of caregiver's distress. The pharmacological treatment of apathy in PD is the focus of this systematic review. Methods: A comprehensive search and systematic selection was performed in different databases of original research papers on the treatment of apathy in PD. The results were then consolidated, and a critical analysis was made of the research papers. The results are then discussed according to the methodological standards for systematic reviews of the literature. Results: A total of 11 studies were included. Although some studies showed efficacy, all of them had important methodological limitations that hampered the interpretation of results. The results of the examined studies cannot be considered as evidence for guiding clinical decisions. Conclusions: So far, no evidence-based recommendations can be offered for the treatment of apathy in PD. More studies with better methodological quality are needed. It is a potentially fruitful area for research and one badly needed by both PD patients and their caregivers.
Asunto(s)
Humanos , Masculino , Femenino , Enfermedad de Parkinson , Terapéutica , Apatía , Calidad de Vida , Esquizofrenia , Afecto , Demencia , Depresión , Quimioterapia , Trastornos Mentales , MétodosRESUMEN
INTRODUCTION AND OBJECTIVES: Apathy, defined as a deficit for initiating and maintaining action, is a symptom affecting patients with diverse psychiatric and neuropsychiatric diseases, including dementia, sequelae of traumatic brain injury, schizophrenia, depression, and Parkinson's disease (PD). Apathy negatively affects function and quality of life of PD patients, and it is an important cause of caregiver's distress. The pharmacological treatment of apathy in PD is the focus of this systematic review. METHODS: A comprehensive search and systematic selection was performed in different databases of original research papers on the treatment of apathy in PD. The results were then consolidated, and a critical analysis was made of the research papers. The results are then discussed according to the methodological standards for systematic reviews of the literature. RESULTS: A total of 11 studies were included. Although some studies showed efficacy, all of them had important methodological limitations that hampered the interpretation of results. The results of the examined studies cannot be considered as evidence for guiding clinical decisions. CONCLUSIONS: So far, no evidence-based recommendations can be offered for the treatment of apathy in PD. More studies with better methodological quality are needed. It is a potentially fruitful area for research and one badly needed by both PD patients and their caregivers.
Asunto(s)
Apatía/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Calidad de Vida , Cuidadores/psicología , Humanos , Enfermedad de Parkinson/fisiopatologíaRESUMEN
Pentatricopeptide repeat (PPR) proteins have been identified as site-specific factors for RNA editing in plant organelles. These proteins recognize cis-elements near the editing site. It is unclear how contiguous sites are addressed, and whether one or two factors are required. We here show the PPR MEF25 to be essential for RNA editing at the nad1-308 site in Arabidopsis mitochondria. Another editing site just one nucleotide upstream, nad1-307, is edited normally in mef25 mutant lines. This finding shows that two independent factors recognizing similar cis-elements are involved at these contiguous sites without competing with each other in vivo.