Effect of a low versus intermediate tidal volume strategy on pulmonary complications in patients at risk of acute respiratory distress syndrome-a randomized clinical trial.

Introduction: There is no consensus on whether invasive ventilation should use low tidal volumes (VT) to prevent lung complications in patients at risk of acute respiratory distress syndrome (ARDS). The purpose of this study is to determine if a low VT strategy is more effective than an intermediate VT strategy in preventing pulmonary complications. Methods: A randomized clinical trial was conducted in invasively ventilated patients with a lung injury prediction score (LIPS) of >4 performed in the intensive care units of 10 hospitals in Spain and one in the United States of America (USA) from 3 November 2014 to 30 August 2016. Patients were randomized to invasive ventilation using low VT (≤ 6 mL/kg predicted body weight, PBW) (N = 50) or intermediate VT (> 8 mL/kg PBW) (N = 48). The primary endpoint was the development of ARDS during the first 7 days after the initiation of invasive ventilation. Secondary endpoints included the development of pneumonia and severe atelectases; the length of intensive care unit (ICU) and hospital stay; and ICU, hospital, 28- and 90-day mortality. Results: In total, 98 patients [67.3% male], with a median age of 65.5 years [interquartile range 55-73], were enrolled until the study was prematurely stopped because of slow recruitment and loss of equipoise caused by recent study reports. On day 7, five (11.9%) patients in the low VT group and four (9.1%) patients in the intermediate VT group had developed ARDS (risk ratio, 1.16 [95% CI, 0.62-2.17]; p = 0.735). The incidence of pneumonia and severe atelectasis was also not different between the two groups. The use of a low VT strategy did neither affect the length of ICU and hospital stay nor mortality rates. Conclusions: In patients at risk for ARDS, a low VT strategy did not result in a lower incidence of ARDS than an intermediate VT strategy.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02070666.

Intoxicación sistémica por anestésicos locales / Systemic intoxication by local anesthetics

Resumen: Los anestésicos locales se definen como fármacos que bloquean la generación y propagación de impulsos en tejidos excitables desde médula ósea, raíces nerviosas, nervios periféricos hasta otros tejidos excitables como músculo cardíaco, músculo liso y cerebro. La intoxicación sistémica se produce debido a las concentraciones plasmáticas elevadas después de altas dosis o la administración intravenosa inadvertida. El creciente uso de técnicas de anestesia locorregional obliga a tener presente la intoxicación sistémica por anestésicos locales como una complicación anestésica de baja incidencia, pero alta morbimortalidad, además de constituir una de las causas de paro cardiorrespiratorio de origen anestésico más frecuentes. La presentación clínica de esta complicación es muy variable y abarca un gran espectro de síntomas relacionados principalmente con la toxicidad neurológica y cardiovascular. Aunque infrecuentes, las reacciones pueden ser muy graves, y resultar en daño irreversible o muerte del paciente. La prevención parece haber disminuido la intoxicación de los anestésicos locales y es más efectiva que el tratamiento. El manejo se basa en medidas de reanimación cardiopulmonar avanzada, el tratamiento farmacológico y el empleo precoz de las emulsiones lipídicas. Se presenta un caso de intoxicación sistémica utilizando lidocaína simple como único anestésico local durante la realización de bloqueo de nervio periférico en cirugía electiva.

Abstract: The local anesthesics are defined as medicaments that block the generation and spread of impulses in excitable fabrics, from bony marrow, nervous roots, peripheral nerves or other excitable fabrics as cardiac muscle, smooth muscle and brain. The systemic intoxication takes place due to the plasmatic concentrations raised after high doses or the intravenous inadvertent administration. The increasing use of technologies of anesthesia locorregional forces to bear in mind the systemic intoxication for local anesthesics as an anesthesic complication of low incident, but high morbi-mortality, beside constituting one of the more frequent reasons of cardiorespiratory unemployment of anesthesic origin. The clinical presentation of this complication is very variable and includes a great spectrum of symptoms related principally to the neurological and cardiovascular toxicity. Though infrequent, the reactions can be very serious, and to result in irreversible hurt or death of the patient. The prevention seems to have diminished the poisoning of the local anesthesics and is more effective than the treatment. The managing is based on measures of resuscitation cardiopulmonar advanced, the pharmacological treatment and the precocious employment of the lipid emulsions. I present a case of systemic intoxication using lidocaine simply as anesthesic local only one during the accomplishment of blockade of peripheral nerve in elective surgery.

Factores relacionados con la duración de lactancia materna exclusiva en madres trabajadoras de una institución universitaria ecuatoriana

RESUMEN Introducción: Ecuador no cubre las recomendaciones de mantener la lactancia materna hasta los seis meses de edad del recién nacido. Objetivo: Analizar los factores relacionados con la duración de la lactancia materna exclusiva en madres trabajadoras de una institución universitaria ecuatoriana. La población de estudio. Métodos: Estudio cuantitativo, descriptivo, transversal, con carácter retrospectivo mediante un cuestionario diseñado ad hoc que se invitó a cumplimentar a todas las madres trabajadoras que lo habían sido en los últimos 10 años de la institución. El período de ejecución del estudio fue de septiembre 2018 a junio de 2019. Resultados: Participaron 316 madres, 62,8 % recibió información sobre lactancia materna y proveniente del médico 55,6 %. La primera hora de vida amamantaron 63,9 %. Más de la mitad de las participantes amamantaron durante un periodo de 6 meses (56,9 %), con lactancia materna exclusiva una media de 4,56 meses. El principal motivo para el abandono fue hipogalactia (26,9 %); incorporación al trabajo (19,2 %); enfermedad materna (5,1 %). La media de lactancia materna exclusiva fue mayor en las madres docentes e investigadoras 4,79 (DE ± 1,8) que en las administrativas y de servicios 4,2 (DE ± 2,05), p= 0,012. Conclusiones: Entre los factores que favorecen la lactancia materna están la información durante el embarazo, así como instaurarla en la primera hora de vida. La situación laboral de la mujer influye en el mantenimiento de dicha lactancia por más tiempo y es una causa de abandono, aunque la más frecuente son los problemas de salud de la madre o del recién nacido.

ABSTRACT Introduction: Ecuador does not cover the recommendations to maintain breastfeeding until six months of age of the newborn. Objective: Analyze the factors related to the duration of exclusive breastfeeding in working mothers of an Ecuadorian university institution. The study population. Methods: Quantitative, descriptive, cross-sectional study, with retrospective character using a questionnaire designed ad hoc; all working mothers who had been in the last 10 years in the institution were invited to fill it. The study was carried out from September 2018 to June 2019. Results: 316 mothers participated, 62.8% received information on breastfeeding and 55.6% from the doctor. The first hour of life, 63.9% mothers breastfed. More than half of the participants breastfed for a period of 6 months (56.9%), and with exclusive breastfeeding during an average of 4.56 months. The main reason for not breastfeeding was hypogalactia (26.9%); work placement (19.2%); maternal disease (5.1%). The mean of exclusive breastfeeding was higher in mother who are teachers and researchers (4.79) (SD ± 1.8) than in mothers with administrative and service positions 4.2 (SD ± 2.05), p = 0.012. Conclusions: Among the factors that favor breastfeeding are information during pregnancy, as well as establishing it in the first hour of life. The employment situation of women influences the maintenance of breastfeeding for longer and is a cause of dropout, although the most frequent are the health problems of the mother or the newborn.

Expanding the clinical phenotype of FGFR1 internal tandem duplication.

Closed spinal dysraphism (SD) is a type of neural tube defect originating during early embryonic development whereby the neural tissue of the spinal defect remains covered by skin, often coinciding with markers of cutaneous stigmata. It is hypothesized that these events are caused by multifactorial processes, including genetic and environmental causes. We present an infant with a unique congenital midline lesion associated with a closed SD. Through comprehensive molecular profiling of the intraspinal lesion and contiguous skin lesion, an internal tandem duplication (ITD) of the kinase domain of the fibroblast growth factor receptor 1 (FGFR1) gene was found. This ITD variant is somatic mosaic in nature as supported by a diminished variant allele frequency in the lesional tissue and by its absence in peripheral blood. FGFR1 ITD results in constitutive activation of the receptor tyrosine kinase to promote cell growth, differentiation, and survival through RAS/MAPK signaling. Identification of FGFR1 ITD outside of central nervous system tumors is exceedingly rare, and this report broadens the phenotypic spectrum of somatic mosaic FGFR1-related disease.

Long-read whole genome sequencing reveals HOXD13 alterations in synpolydactyly.

Synpolydactyly 1, also called syndactyly type II (SDTY2), is a genetic limb malformation characterized by polydactyly with syndactyly involving the webbing of the third and fourth fingers, and the fourth and fifth toes. It is caused by heterozygous alterations in HOXD13 with incomplete penetrance and phenotypic variability. In our study, a five-generation family with an SPD phenotype was enrolled in our Rare Disease Genomics Protocol. A comprehensive examination of three generations using Illumina short-read whole-genome sequencing (WGS) did not identify any causative variants. Subsequent WGS using Pacific Biosciences (PacBio) long-read HiFi Circular Consensus Sequencing (CCS) revealed a heterozygous 27-bp duplication in the polyalanine tract of HOXD13. Sanger sequencing of all available family members confirmed that the variant segregates with affected individuals. Reanalysis of an unrelated family with a similar SPD phenotype uncovered a 21-bp (7-alanine) duplication in the same region of HOXD13. Although ExpansionHunter identified these events in most individuals in a retrospective analysis, low sequence coverage due to high GC content in the HOXD13 polyalanine tract makes detection of these events challenging. Our findings highlight the value of long-read WGS in elucidating the molecular etiology of congenital limb malformation disorders.

Projection of E-Learning in Higher Education: A Study of Its Scientific Production in Web of Science.

E-learning is conceived as a purely virtual training approach. Different learning styles have been proliferated in recent years, especially now, due to the impact of COVID-19 in the educational field. The aim of this study is to discover the evolution of e-learning in higher education (ELHI) in scientific literature indexed on the Web of Science. Co-word analysis and bibliometric analysis was performed. A total matrix of 1261 documents was analyzed through SciMAT software. The results revealed that studies on ELHI are written in English and presented by conference papers. The main source of publication for the conferences is EDULEARN proceedings, while the journal source is Procedia-Social and Behavioral Sciences. Spain is the country with the highest volume of production. It is concluded that research on ELHI use does not have an established line of research, due to its recent creation and the lack of related research. The bibliometric analysis specifies that the research is oriented towards knowing the level of acceptance and application of the pedagogical method in the teaching and learning processes.

Adaptation and Validation of the Motivated Strategies for Learning Questionnaire for Spanish Adolescents.

This work adapts and validates the scale of the motivated strategies for learning questionnaire (MSLQ), which is used to measure motivation. For this, an instrumental design was carried out with the purpose of analyzing the psychometric properties of the instrument. The sample consisted of 307 participants enrolled in compulsory secondary education. Reliability with fit indices were good in model B (proposed) with composite reliability, global reliability index, and Cronbach's alpha. The original model (A) presented small problems that had to be adjusted when carrying out the translation. We concluded that adaptation and subsequent validation of the MSLQ instrument into a Spanish context was positive. In this sense, adequate adjustment rates have been achieved. However, in its contextual adequacy, the need arises to modify the presentation of the items alluding to intrinsic motivation due to the difficulty of measuring such a construct. Among the implications reached in this study is the possibility of having a validated instrument for the Spanish adolescent context to measure motivation on educational aspects. Furthermore, this tool can serve as the basis for the design of other instruments that measure this construct in other age ranges.

Eye Salvage with Intra-Arterial and Intra-Vitreal Chemotherapy in Patients with Retinoblastoma: 8-Year Single-Institution Experience in Colombia.

INTRODUCTION: Intra-arterial chemotherapy (IAC) is useful for eye preservation in advanced retinoblastoma (Rb). Intra-vitreal chemotherapy (IvitC) is the latest treatment for vitreous seeds. METHODS: The present study is a retrospective assessment of 100 eyes, treated with primary or secondary IAC alone or with IvitC. We evaluated demographic and clinical variables, eye salvage, associated adverse events, and patient survival. Data were analyzed using descriptive statistics. Kaplan-Meier survival curves and Cox hazard ratios were utilized to assess the effect of demographic and clinical variables over eye salvage. RESULTS: Bilateral Rb was observed in 61% of patients, and 57% of eyes received secondary treatment. Forty eyes needed intra-arterial plus IvitC and 62 presented advanced disease (group D and E). Three- and 5-year ocular survival probabilities were 75 and 68%. We found a higher risk in group D and E eyes and those requiring 2 or more routes for ophthalmic artery catheterization. Patients coming from other countries also showed increased risk. Using primary or secondary treatment, or IvitC, did not affect this risk. Overall rates of survival and eye salvages were 98.8 and 73%, and we had a 100% catheterization success and none ophthalmic arterial occlusions. CONCLUSIONS: In an upper middle-income country such as Colombia, a specialized institution counting with therapeutic alternatives and a multidisciplinary team can reach rates of patient survival and eye salvage similar to those of high-income countries.

Spanish Adaptation and Validation of the Teaching and Learning Experiences Questionnaire.

Training processes are mainly based on the pedagogical methods applied by teachers. In many cases, these pedagogical methods are adapted to the social, economic, and cultural environment of the students themselves. In this study, we used a psychometric analysis based on the analysis of structural equations to detect the psychometric properties through classical goodness-of-fit indices. The objective of this study was to translate, adapt, and validate the instrument called the Teaching and Learning Experiences Questionnaire (ETLQ) for the population of Spanish adolescents in secondary education. The rrecommendations in the literature were followed for its translation and adaptation into Spanish. The results indicate that, after translation and adaptation, the model remained in 11 factors with acceptable goodness-of-fit indices. We conclude that the process of translation, adaptation, and validation of the ETLQ has produced a valid and reliable tool due to the psychometric findings revealed in the present work.

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma.

Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.

Effects on Personal Factors Through Flipped Learning and Gamification as Combined Methodologies in Secondary Education.

PURPOSE: This study aims to analyze the effects of a flipped and gamified program on the autonomy, competence, relation with others, satisfaction/enjoyment, intrinsic and extrinsic motivation, and boredom of students of Physical Education. METHOD: The study used a control group and an experimental group to compare pretest and posttest data in both of them. Instruments used were the Basic Psychological Needs in Exercise Scale, Sport Motivation Scale, and Sport Satisfaction Instrument, all of them validated in academic literature. RESULTS: On one hand, data indicated that autonomy has been increased with the application of these teaching methodologies. On the other hand, students' satisfaction, enjoyment, and intrinsic motivation have improved based on the interaction with gamification and flipped learning. Finally, with all dimensions, it seems that academic performance has been improved, although not in a significative way. DISCUSSION/CONCLUSION: Results of the study provide to educational researchers valuable information for a better understanding of how flipped learning and gamification influence personal performance of Physical Education students.

Response to SARS-CoV-2 Pandemic in a Non-COVID-19 Designated Latin-American Neurosurgery Department.

Background: Mexico declared the first case of novel coronavirus disease (COVID-19) in February 2020. At the time we write this article, our country is facing a community spread phase, expecting a rapid increase in the number of cases and fatalities. The Fray Antonio Alcalde Civil Hospital of Guadalajara has been declared a non-COVID-19 hospital with the mission of providing care to patients already registered and also those transferred from neurosurgical departments of neighboring centers, which have been converted into COVID-19 only hospitals. Methods: An organized response regarding personnel, surgical case selection, operating room behavior, and facility reorganization were designed to prevent an internal coronavirus outbreak in the neurosurgery department at the Fray Antonio Alcalde Civil Hospital of Guadalajara. Results: Distancing actions by the staff and residents, including ward case discussions, neurosurgery rounds, and classes, will be carried out virtually. We classified neurosurgical patients into 4 groups depending on whether their condition demands care in 0-6 hours, 6-48 hours, 48 hours to 14 days, and >14 days. Subsequently, a questionnaire with epidemiologic, radiologic, clinical, and serologic criteria will be applied to determine the risk of COVID-19 infection to define to which area they are going to be transferred according to the different risk zones in our facility. Conclusions: Despite not being a COVID-19 center, we consider all patients at the neurosurgical ward and staff members as asymptomatic carriers or infected in the preclinical period. Specific measures must be taken to ensure the safety and care of neurosurgical patients and medical staff during the community spread phase.

Evaluating Activation and Absence of Negative Effect: Gamification and Escape Rooms for Learning.

Innovation has allowed for and developed new ways of teaching and learning. Gamification is among the new training methodologies, which is a didactic approach based on the game structure with an attractive component for students. Within gamification, flipped learning and problem-based learning, escape rooms can be found as a technical aspect, which is focused on providing enigmas and tracks for the various educational content that students have assimilated through learning based on problem solving. The aim of this study is to identify how the use of gamification with the use of educational escape rooms affects activation and absence of a negative effect on students. 61 Master students of the Autonomous City of Ceuta participated in this case study. They were divided into three study groups (1 control group; 2 experimental groups) that followed different formative actions (control group-traditional; experimental groups-escape rooms). To achieve the objectives, a mixed research design based on quantitative and qualitative techniques was followed. The instrument used for data collection was the GAMEX (Gameful Experience Scale). The results reveal that the students who had taken a gamified formative action through escape rooms obtained better assessment results in the indicators concerning motivation, teamwork, commitment, activation, and absence of a negative effect on the learning process than those with the traditional methodology.

Suicidal Ideation, Psychological Distress and Child-To-Parent Violence: A Gender Analysis.

Child-to-parent violence (CPV) is a growing public health problem with consequences for perpetrators and families. Most research has focused on individual and family risk factors. However, little is known about its links with individual outcomes. The aim of this study was to analyze the relationships between CPV and psychological distress, suicidal ideation, and self-concept in school-aged adolescents, taking into account the gender perspective. A study was conducted with a sample of 8,115 adolescents, aged between 11 and 16 years (M = 13.34; SD = 1.04) from the State of Nuevo León, Mexico. A MANOVA 3 × 2 was performed to analyze the data. The results revealed that adolescents involved in CPV showed higher levels of psychological distress and suicidal ideation and lower levels of family and social self-concept. It was also observed that girls with higher levels of CPV scored the lowest levels of psychological distress and suicidal ideation, as well as the lowest levels of family self-concept. The findings highlight that adolescents and especially girls involved in CPV also report internal maladjustment outcomes. Finally, the results and their implications for research and intervention with adolescents involved in CPV are discussed.

Tutorial Action and Emotional Development of Students as Elements of Improved Development and Preventing Problems Related with Coexistence and Social Aspects.

Integral development of students is promoted through tutorial action. Tutorial action is understood as the personal development of students, their learning, and their capabilities for social and labour integration. A descriptive, nonexperimental and ex post facto design was used. The sample consisted of 569 primary school students. The importance of emotional education and student tutoring was highlighted by the results produced. A relationship was established between working on emotions and emotional regulation, cognitive re-evaluation, and capacity to respond in an emotionally appropriate way when faced with different situations.

Analysis of the Acid Detergent Fibre Content in Turnip Greens and Turnip Tops (Brassica rapa L. Subsp. rapa) by Means of Near-Infrared Reflectance.

Standard wet chemistry analytical techniques currently used to determine plant fibre constituents are costly, time-consuming and destructive. In this paper the potential of near-infrared reflectance spectroscopy (NIRS) to analyse the contents of acid detergent fibre (ADF) in turnip greens and turnip tops has been assessed. Three calibration equations were developed: in the equation without mathematical treatment the coefficient of determination (R2) was 0.91, in the first-derivative treatment equation R2 = 0.95 and in the second-derivative treatment R2 = 0.96. The estimation accuracy was based on RPD (the ratio between the standard deviation and the standard error of validation) and RER (the ratio between the range of ADF of the validation as a whole and the standard error of prediction) of the external validation. RPD and RER values were of 2.75 and 9.00 for the treatment without derivative, 3.41 and 11.79 with first-derivative, and 3.10 and 11.03 with second-derivative. With the acid detergent residue spectrum the wavelengths were identified and associated with the ADF contained in the sample. The results showed a great potential of NIRS for predicting ADF content in turnip greens and turnip tops.

Family Communication Problems, Psychosocial Adjustment and Cyberbullying.

The aim of the present study was to analyze the relationship between family communication problems and cyberbullying, through psychosocial adjustment-psychological distress, attitude towards institutional authority, and problematic use of social networking sites-in adolescents. Random sampling by conglomerates was performed. A total of 8115 adolescents participated in the study (51.5% boys, 49.5% girls), and were aged between 11 and 16 years old (M = 13.34, SD = 1.04) and enrolled in the State of Nuevo León (Mexico). A structural equations model was developed using the Structural Equation Modeling Software (EQS). The results showed that problematic family communication is directly associated with cyberbullying, and also indirectly through the relationships of psychological distress and attitude towards transgression of social norms with the problematic use of social networking sites. The multi-group analyses also revealed gender differences in these relationships. Finally, the obtained results were discussed and their practical implications were shown.

Biological properties of electrospun cellulose scaffolds from biomass.

Nowadays the development of sustainable technologies for the effective production of polymeric materials that can be used as biomaterials will be of importance. In this work, cellulose (CEL) was purified from potato peel waste (PPW) and used to produce electrospun nanofibers for tissue engineering applications. The purified CEL was solubilized in copper ethylenediamine (Cuen) and the electrospun nanofibers was produced through electrospinning technique in diameter range of 250-500 nm at electrical field strength of 20 kV. To confirm the applicability of the electrospun CEL scaffolds in tissue engineering, in vitro BALB-3T3 fibroblastic cell adhesion and cell proliferation tests were employed in this study. Cell viability was evaluated by staining with ethidium bromide (EtBr) and acridine orange (AO) to evaluate the possible effects of cytotoxicity of the CNF scaffolds. Fluorescence studies confirmed that BALB-3T3 viable cells attached and spread throughout the CEL scaffold. The attachment and spreading of viable cells suggests that electrospun CEL scaffolds support growth of BALB-3T3 fibroblasts cells and suggests that PPW can be a useful source of raw material for the production of scaffolds for tissue engineering.

Polyunsaturated Fatty Acid Desaturation Is a Mechanism for Glycolytic NAD+ Recycling.

The reactions catalyzed by the delta-5 and delta-6 desaturases (D5D/D6D), key enzymes responsible for highly unsaturated fatty acid (HUFA) synthesis, regenerate NAD+ from NADH. Here, we show that D5D/D6D provide a mechanism for glycolytic NAD+ recycling that permits ongoing glycolysis and cell viability when the cytosolic NAD+/NADH ratio is reduced, analogous to lactate fermentation. Although lesser in magnitude than lactate production, this desaturase-mediated NAD+ recycling is acutely adaptive when aerobic respiration is impaired in vivo. Notably, inhibition of either HUFA synthesis or lactate fermentation increases the other, underscoring their interdependence. Consistent with this, a type 2 diabetes risk haplotype in SLC16A11 that reduces pyruvate transport (thus limiting lactate production) increases D5D/D6D activity in vitro and in humans, demonstrating a chronic effect of desaturase-mediated NAD+ recycling. These findings highlight key biologic roles for D5D/D6D activity independent of their HUFA end products and expand the current paradigm of glycolytic NAD+ regeneration.