Development of simplified sampling methods for behavioural data in rabbit does

[EN] The aim of this study was to compare the results of different simplified sampling methods for behavioural data compared to reference records of 24-h in order to assess rabbit doe behaviours at different physiological stages (gestation and lactation) in animals housed in 2 types of cages (conventional and alternative). In total, we analysed 576 h of continuous video of 12 rabbit does at the end of lactation and the same females after weaning. The behavioural observations were studied using 3 independent categories of classification (location in the cage, posture and functional behaviours). Continuous behavioural recordings of 24 h were considered as the reference method to validate another 4 data collection sampling methods by aggregated video recordings of different frequency and duration [regular short and long methods with 2.4 and 8 h of observation respectively, and irregular (more frequent during the active period) short and long methods with 6 and 8 h of observation, respectively]. The current results showed that, independently of the housing system, the best method to reduce the total observation time required to assess rabbit does’ behaviour depends on the trait studied and physiological stage of the does. In gestating does, irregular methods were not suitable to estimate behaviours of long duration such as lying, sitting, resting and grooming. However, in both physiological stages, regular methods were accurate for location behaviours, postures and functional behaviours of long duration. Instead, for the study of infrequent behaviours performed mainly during dark period, where coefficients of variation were high, the irregular long method led to the lowest mean estimation errors.Alfonso-Carrillo, C.; Martín, E.; Blas, CD.; Ibáñez, M.; García-Ruiz, A.; García-Rebollar, P. (2017). Development of simplified sampling methods for behavioural data in rabbit does. World Rabbit Science. 25(1):87-94. doi:10.4995/wrs.2017.3627SWORD879425

Comprimidos bucodispersables: ventajas terapéuticas y tecnológicas de elaboración

Los comprimidos bucodispersables se definen como comprimidos no recubiertos destinados a ser colocados en la boca, donde se dispersan rápidamente antes de ser tragados. Estas formulaciones son conocidas por las siglas FDDT´s (Fast Dissolving Disintegrating Tablets). Son útiles para la administración a pacientes con dificultades en la deglución, presentan una elevada aceptación por parte del paciente, mejoran de la biodisponibilidad del principio activo y suponen una nueva alternativa para la industria farmacéutica. Dentro de sus inconvenientes destacan el poco conocimiento por parte del paciente, la baja resistencia mecánica, su mayor susceptibilidad a la degradación por temperatura y humedad; la falta, a veces, de bioequivalencia con las formulaciones convencionales, y la dificultad de obtener liberaciones prolongadas o retardadas del principio activo. A nivel tecnológico, existen varios procesos que se pueden aplicar en su elaboración. Con los métodos clásicos de elaboración de comprimidos, mediante la correcta selección de los excipientes y de las variables de la etapa de compresión se obtienen unos comprimidos en los que existe un equilibrio entre dureza y disgregación. Han surgido una serie de tecnologías novedosas: Flashtab, Wowtab, Orasolv y Durasolv. Otra opción es el empleo de técnicas de liofilización, aunque presenta como desventaja su alto coste. Algunas tecnologías especiales patentadas como son Lyoc, QuickSolv y Zydis. Por último, estos comprimidos se pueden elaborar por el método de los polímeros entrecruzados, también conocido como FlashDose y se basa en la formación de una matriz de hilos de azúcares entrelazados.Orally Disintegrating Tablets are defined as non-coated tablets that are placed in the mouth, where they are rapidly disintegrated before being swallowed. These formulations are known by the acronym FDDT's (Fast Dissolving Disintegrating Tablets). They are useful for administration to patients with difficulties in swallowing, present high acceptance by the patient, improve the bioavailability of the active pharmaceutical ingredient and represent a new alternative for the pharmaceutical industry. Among their disadvantages are the lack of knowledge by the patient, the low hardness and friability, their major degradation susceptibility by temperature and moisture environment, the non bioequivalence with the conventional formulations that sometimes happens and finally the difficulty to obtain prolonged or delayed drug release. From a pharmaceutical technological point of view, there are several processes that can be applied in their preparation. With the conventional tableting technology, choosing a proper role of excipients and variables in the compression stage, tablets with a good balance between hardness and disgregation must be obtained. A series of innovative technologies have been arisen: Flashtab, Wowtab, Orasolv and Durasolv. Another option is the use of freeze drying technique, although it high cost represents a significantly disadvantage. There are some special patented technologies such as Lyoc, QuickSolv and Zydis. Finally, these tablets can be produced by the method of interlocking polymers, also known as FlashDose base on the formation of a matrix of interwoven threads of sugar

Phase diagram of a superconductor / ferromagnet bilayer

The magnetic field (H) - temperature (T) phase diagram of a superconductor is significantly altered when domains are present in an underlying ferromagnet with perpendicular magnetic anisotropy. When the domains have a band-like shape, the critical temperature Tc of the superconductor in zero field is strongly reduced, and the slope of the upper critical field as a function of T is increased by a factor of 2.4 due to the inhomogeneous stray fields of the domains. Field compensation effects can cause an asymmetric phase boundary with respect to H when the ferromagnet contains bubble domains. For a very inhomogeneous domain structure, Tc~H^2 for low H and Tc~H for higher fields, indicating a dimensional crossover from a one-dimensional network-like to a two-dimensional behavior in the nucleation of superconductivity.Comment: 6 pages, 7 figure

Verbal fluency tests: Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the phonological and semantic verbal fluency tests (VFT) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the VFT as part of a larger neuropsychological battery. Scores for letters F, A, S, and animals and fruit categories were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, such that scores increased linearly as a function of age. Age2 had a significant effect in Chile (animals), Cuba (A letter, fruits), Ecuador (animals, fruits), Honduras (F letter), Mexico (animals, fruits), Peru (fruits), and Spain (S letters, animals, fruits). Models showed an effect for MLPE in Chile (A letters, animals, fruits), Ecuador (S letter, animals, fruits), Guatelama (F, S letter, animals), Honduras (animals), Mexico (F, A, S letters, animals, fruits), Puerto Rico (A, letters, animals), and Spain (all scores). Sex scores were found significant in Chile (animals), Ecuador (A letter, fruits), Mexico (F letter, fruits), Paraguay (F, A, S letters, fruits), Puerto Rico (F letter, animals, fruits), and Spain (F letter, fruits). CONCLUSIONS: This is the largest multi-national Spanish speaking-pediatric normative study in the world, and as such it will allow neuropsychologists from these countries to have a more accurate way to interpret the phonological and semantic VFT in pediatric populations

Newly developed Learning and Verbal Memory Test (TAMV-I): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Learning and Verbal Memory Test (TAMV-I) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the TAMV-I as part of a larger neuropsychological battery. Free recall, memory delay and recognition scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that scores increased linearly as a function of age. Age2 had a significant effect in all countries except Cuba, and Puerto Rico for free recall score; a significant effect for memory delay score in all countries except Cuba and Puerto Rico; and a significant effect for recognition score in in all countries except Guatemala, Honduras, and Puerto Rico. Models showed an effect for MLPE in Chile (free recall), Honduras (free recall), Mexico (free recall), Puerto Rico (free recall, memory delay, and recognition), and Spain (free recall and memory delay). Sex affected free recall score for Cuba, Ecuador, Guatemala, Mexico, Paraguay, Peru, and Spain, memory delay score for all countries except Chile, Paraguay, and Puerto Rico, and recognition score for Ecuador, Mexico, Peru, and Spain, with girls scoring higher than boys. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the TAMV-I with pediatric populations

Concentration Endurance Test (d2): Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Concentration Endurance Test (d2) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the d2 test as part of a larger neuropsychological battery. The Total number of items processed (TN), Total number of correct responses (CR), Total performance (TP), and Concentration performance (CP) scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, such that scores increased linearly as a function of age. TN scores were affected by age2 for Guatemala and Puerto Rico; CR scores were affected by age2 for Mexico; TP scores were affected by age2 for Chile, Mexico, Puerto Rico, and Spain; and CP scores for Mexico and Spain. Models indicated that children whose parents had a MLPE >12 years obtained higher scores compared to children whose parents had a MLPE≤12 years for Mexico and Spain in all scores, and Puerto Rico for TN, CR, and TP, and Guatemala and Paraguay for CP scores. Sex affect the scores for Ecuador and Honduras (CP scores). CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the d2 test in pediatric populations

Assessment of a Genomic Assay in Patients with ERBB2 -Positive Breast Cancer Following Neoadjuvant Trastuzumab-Based Chemotherapy with or Without Pertuzumab

Importance: Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed. Objective: To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. Design, Setting, and Participants: This is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy. Exposures: Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles. Main Outcome and Measures: Association of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab. Results: The assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P <.001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P <.001). In the combined analysis (n = 282), an increase in pCR rate due to pertuzumab was found in the assay-reported pCR-high tumors (OR, 5.36; 95% CI, 1.89-15.20; P <.001) but not in the assay-reported pCR-low tumors (OR, 0.86; 95% CI, 0.30-2.46; P =.77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed. Conclusions and Relevance: This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab