Rapid assessment of enhanced safety surveillance for influenza vaccine.

OBJECTIVES: The enhanced safety surveillance for seasonal influenza vaccines established by the European Medicines Agency is required each season. Therefore, a registry capable of rapidly detecting and evaluating potential new safety concerns is needed. The aim of the study is to demonstrate the effectiveness of the vaccine information system of the Valencia region to make a rapid assessment of the influenza vaccine safety and describe the safety of the two vaccine types used in the 2017/2018 season. STUDY DESIGN: It is a population-based descriptive study. METHODS: Adverse events following immunization reports collected from 23rd October 2017 to 15th March 2018 were analyzed. RESULTS: A total of 55 adverse events for influenza vaccine were reported in season 2017/2018 with a reporting rate (RR) of 0.77 per 10,000 administered doses. Injection site reactions had a RR of 0.30 and 0.47 per 10,000 for subunit and adjuvanted vaccines, respectively. Differences per vaccine, sex, and risk group did not reach statistical significance. CONCLUSIONS: Reported events of the two influenza vaccine types used were similar than in other seasons and consistent with their safety profiles.

Nontargeted Analytical Methods as a Powerful Tool for the Authentication of Spices and Herbs: A Review.

Food fraud in herbs and spices is an important topic, which has led to new technologies being studied as potential tools for fraud identification. Nontargeted technologies have proven to be a useful tool for the authentication of herbs and spices. The present review focuses on the use of near-infrared, hyperspectral imaging, Fourier-transform infrared, Raman, nuclear magnetic resonance, and electron spin resonance spectroscopy for the authentication of spices, which includes the determination of origin and irradiated spices and the identification of adulterants. The methods developed based on vibrational spectroscopy combined with chemometric techniques seem to be promising tools for determining the presence of adulterants and contaminants in herbs and spices. On the other hand, nuclear magnetic resonance seems to be the most efficient technology to determine the origin of herbs and spices although, for some cases, studies with near-infrared spectroscopy can be a viable substitute. Electron spin resonance spectroscopy is the technique par excellence used for the authentication of irradiated herbs and spices, so its use should be expanded to many more spices' varieties. Portable devices are preferred by those involved in the food industry, due to its manageability and low cost. Data fusion and big data are shown as promising tools for spice fraud control. In conclusion, spectroscopic techniques show a great efficiency to authenticate spices, although their evaluation must be expanded to other spice varieties, to new strategies of data analysis (as data fusion and big data), and to the use of portable devices.

Impact of pre-drying and frying time on physical properties and sensorial acceptability of fried potato chips.

In this work the effects of pre-drying and frying time on colour, oil, texture and sensorial acceptability (overall liking) of potato chips were evaluated. Potato chips were pre-dried for 0, 10, 20 and 30 min at 60 °C and fried in soybean oil at 190 °C for 60, 70 and 80 s. The colour parameters (L*, a* and b*) increased or decreased depending on the pre-drying and frying time. Hardness increased as the pre-drying and frying time increased. On the other hand, the water initially removed by pre-drying decrease the gradient of mass transfer (water-oil). The oil content reduced to (about 21%) in pre-dried samples when compared to control sample. Finally, sensorial evaluation showed that samples without pre-drying and/or fried for very short or very long times had low acceptance levels. The pre-drying and frying times influenced the colour, texture, water and oil content, and resulted into fried potato chips with better acceptance scores.

Surveillance for adverse events following immunization (AEFI) for 7 years using a computerised vaccination system.

OBJECTIVES: The surveillance of vaccine safety is an essential requirement in vaccination programmes. Computerized immunization registries such as the Vaccination Information System (SIV) of Valencian Community (Spain) offer the opportunity to estimate the incidence of adverse events according to individual information. The aim of the study was to analyze adverse events following immunization reported through SIV from 2005 to 2011 by age, sex, type of vaccine and dose, and adverse event, and highlight the advantages of this type of reporting. STUDY DESIGN: A retrospective cohort study of subjects vaccinated in the Valencian Community using population health databases was carried out. METHODS: Analysis of vaccinations and reported AEFI via SIV in Valencian Community was carried out. RESULTS: More than 13 million vaccines doses were administered during 2005 through 2011, the reporting rate of adverse events was 12.4/100,000 doses administered with the highest value in 2009 (27.4), with differences by age and sex. DTaP vaccine had the highest reporting in children (96.6/100,000) while influenza A(H1N1)pdm09 in adults (87.7/100,000). An increased reporting of adverse events was seen with DTaP in children 5-6 years of age, detected in real time, drove to swap this vaccine to a low dose Tdap which was followed by a decrease in administration site events. CONCLUSIONS: SIV demonstrates advantages for passive surveillance. Reporting rates by individual characteristics are calculated accurately and it also allows detecting shifts in reporting rate on real time for specific vaccines. The study shows that vaccines included in the routine vaccination schedule for children and adult vaccination programs are safe.

Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation.

The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen.

[Analysis of the echographic parameters described in the study of carpal tunnel syndrome: A systematic review]. / Análisis de los parámetros ecográficos descritos en el estudio del síndrome del túnel del carpo. Una revisión sistemática.

Carpal tunnel syndrome (CTS) is the most common entrapment mononeuropathy; the diagnosis is established by electrodiagnostic tests with until 34% of false positives/negatives. We present the following systematic review which objective is to analyze the most recent literature related to the ultrasound parameters described to study CTS. We selected studies that evaluated ultrasound parameters in patients with clinical suspicion following the Cochrane manual's recommendations. We include systematic reviews, meta-analyses, case-control studies and diagnostic tests, evaluating retrospective studies and bibliographic reviews with proper methodological quality. Articles published between 2005 and 2019. We included eight articles (two systematic reviews/meta-analyses, two case-control studies, one diagnostic test study, two literature reviews, and one retrospective). The parameters analyzed were cross-sectional area, wrist-forearm index, entry-exit index, thinning range, palmar bowing of the flexor retinaculum, and vascularity/mobility. Current evidence allows us to affirm that ultrasound is useful in screening for CTS.

[Tele-rehabilitation in musculoskeletal pathology of the upper and lower limb]. / Telerrehabilitación en patología musculoesquelética de miembro superior e inferior.

Chronic musculoskeletal conditions cause pain and disability and have significant impact on morbidity worldwide. Tele-rehabilitation is proposed as an alternative or complement to improve patient's muscle function, pain, and quality of life. However, the satisfaction of both patients and professionals must be assessed, together with the patient's daily life activity independence. A search of the literature was made to locate assessment reports, systematic reviews and reports from regulatory bodies with support from a documentarian from the Andalusian Health Technologies Assessment Area (AETSA). For this purpose, the following sources were used: Medline, EMBASE, INAHTA (international network of health technologies assessment) and PEDro (Physiotherapy Evidence Database) from 2014 onwards. Subsequently a secondary search was carried out on the articles selected in the initial search. A search of open clinical trials was also carried out in the database: www.ClinicalTrials.gov Initially 345 articles were identified. Duplicated articles (57) were excluded. By first analysing the title and abstract 238 articles were excluded. The full texts of the remaining 30 articles were analysed. Finally 18 articles were included.

[Trifid median nerve. A rare anatomical variant in sonographic evaluation of carpal tunnel]. / Nervio mediano trífido. Una variante anatómica infrecuente en la exploración ecográfica del túnel del carpo.

The ultrasound study for the diagnosis of carpal tunnel syndrome can reveal different anatomical variants. A rare variant is the presence of a trifid median nerve. The visualization of this anatomical variant may be of importance in the surgical planning of carpal tunnel syndrome. Fifty-two-year-old male, with a clinic compatible with bilateral carpal tunnel syndrome. In the ultrasound examination, a bifid median nerve appears as a finding in the right wrist and a trifid median nerve in the left wrist as anatomical variants. It is important to distinguish a trifid median nerve from a persistent median artery at the level of the carpal tunnel, much more frequent than the first. For this, the ultrasound visualization of the study area using the Doppler function is essential.

[Objective measurement tools that predict success in the fitting of major unilateral lower limb amputations patients]. / Instrumentos predictores del éxito en la protetización de pacientes con amputaciones unilaterales mayores de miembro inferior.

The profile of the patient who most frequently suffers lower limb amputations is usually an elderly patient with high comorbidity. Physiatrists need objective tools in the assessment of these patients that predict the results of prosthetic programs to increase patient safety and efficiency of prosthetic rehabilitation programs. Given the need to update scientific knowledge in this field, we have carried out a review of the literature with the aim of defining a proposal for tools that facilitate decision-making in the indication of prosthetic rehabilitation in these patients. A bibliographic search strategy has been carried out using the scientific databases PubMed, Web of Science, Scopus and Cochrane Library. The quality of the selected articles has been assessed according to the tools proposed by CASPe.

Management of non-hepatic distant metastases in neuroendocrine neoplasms.

Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.

Rapid and non-destructive cinnamon authentication by NIR-hyperspectral imaging and classification chemometrics tools.

Cinnamon is a valuable aromatic spice widely used in pharmaceutical and food industry. Commonly, two-cinnamon species are available in the market, Cinnamomum verum (true cinnamon), cropped only in Sri Lanka, and Cinnamomum cassia (false cinnamon), cropped in different geographical origins. Thus, this work aimed to develop classification models based on NIR-hyperspectral imaging (NIR-HSI) coupled to chemometrics to classify C. verum and C. cassia sticks. First, principal component analysis (PCA) was applied to explore hyperspectral images. Scores surface displayed the high similarity between species supported by comparable macronutrient concentration. PC3 allowed better class differentiation compared to PC1 and PC2, with loadings exhibiting peaks related to phenolics/aromatics compounds, such as coumarin (C. cassia) or catechin (C. verum). Partial least square discriminant analysis (PLS-DA) and Support vector machine (SVM) reached similar performance to classify samples according to origin, with error = 3.3 % and accuracy = 96.7 %. A permutation test with p < 0.05 validated PLS-DA predictions have real spectral data dependency, and they are not result of chance. Pixel-wise (approach A) and sample-wise (approach B, C and D) classification maps reached a correct classification rate (CCR) of 98.3 % for C. verum and 100 % for C. cassia. NIR-HSI supported by classification chemometrics tools can be used as reliable analytical method for cinnamon authentication.

Data reduction by randomization subsampling for the study of large hyperspectral datasets.

Large amount of information in hyperspectral images (HSI) generally makes their analysis (e.g., principal component analysis, PCA) time consuming and often requires a lot of random access memory (RAM) and high computing power. This is particularly problematic for analysis of large images, containing millions of pixels, which can be created by augmenting series of single images (e.g., in time series analysis). This tutorial explores how data reduction can be used to analyze time series hyperspectral images much faster without losing crucial analytical information. Two of the most common data reduction methods have been chosen from the recent research. The first one uses a simple randomization method called randomized sub-sampling PCA (RSPCA). The second implies a more robust randomization method based on local-rank approximations (rPCA). This manuscript exposes the major benefits and drawbacks of both methods with the spirit of being as didactical as possible for a reader. A comprehensive comparison is made considering the amount of information retained by the PCA models at different compression degrees and the performance time. Extrapolation is also made to the case where the effect of time and any other factor are to be studied simultaneously.

Stereotactic body radiotherapy for early-stage non-small cell lung cancer: a multicentre study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE/OBJECTIVE(S): Stereotactic body radiotherapy (SBRT) has become the standard of care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) and for patients who refuse surgery. The aim of this study was to evaluate the effectiveness and safety of primary SBRT in patients with early-stage NSCLC. MATERIALS/METHODS: Retrospective multicenter study of 397 patients (416 primary lung tumours) treated with SBRT at 18 centres in Spain. 83.2% were men. The median age was 74.4 years. In 94.4% of cases, the tumour was inoperable. The pathological report was available in 54.6% of cases. SPSS vs 22.0. was used to perform all statistical analyses. RESULTS: Complete response was obtained in 53.6% of cases. Significant prognostic factors were standard CT planning (p = 0.014) and 4D cone beam CT (p = 0.000). Acute and chronic toxicity ≥ grade 3 was observed in 1.2% of cases. At a median follow-up of 30 months, local relapse was 9.6%, lymph node relapse 12.8%, distant metastasis 16.6%, and another lung tumour 11.5%. Complete response was the only significant prognostic factor for local relapse (p = 0.012) and distant metastasis (p = 0.001). The local relapse-free survival was 88.7%. The overall survival was 75.7%. The cancer-specific survival was 92.7%. The disease-free survival was 78.7%. CONCLUSION: SBRT is an effective and well-tolerated treatment option for patients with early-stage lung cancer who are not suitable for surgery. The most important prognostic factor for local and distant recurrence was complete response, which in our sample depended on the type of CT planning and the IGRT technique.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

[Utilisation of atypical antipsychotic drugs in institutionalised elderly persons and prevalence of metabolic alterations]. / Utilización de fármacos antipsicóticos atípicos en ancianos institucionalizados y prevalencia de alteraciones metabólicas.

OBJECTIVES: Describe and evaluate atypical antipsychotics utilisation on the institutionalized elderly population of the Valencian Community and prevalence of associated metabolic alterations. MATERIAL AND METHODS: Multicentre transversal descriptive study on medication utilisation and prevalence case-control of alterations of glycaemia, cholesterol and triglycerides. The statistical analysis of metabolic alterations is performed from the difference in prevalence and its statistical signification between the control group and the study group. RESULTS: 681 patients were included (study group, 344; control group, 337) from 20 social-health-care centres. 18.5% of the institutionalised patients are being treated with atypical antipsychotics. The most frequent diagnoses are: behavioural alterations associated with dementia (63.6%) and schizophrenia (18.4%). Risperidone is the most frequently used antipsychotic (66.0%). For all the drugs in general the doses used adjust to those recommended for elderly patients. The prevalence of alterations in glycaemia, cholesterol and triglycerides metabolism in the group under study is 23.96%, 34.83%, and 26.29%, respectively, with no statistically significant differences against the control group. The analysis by type of drug did not show significant differences. CONCLUSIONS: The results obtained show that utilisation of atypical antipsychotics in elderly patients complies with the established general recommendations. The doses used in elderly patients with behavioural alterations associated with dementia, mostly treated with risperidone, do not have a significant impact over prevalence increase of metabolic alterations.

[Implementation of a new referral model for the musculoskeletal care pathway: Does it improve healthcare outcomes?] / Implantación de un nuevo modelo organizativo en la atención al proceso musculoesquelético: ¿mejora la capacidad de resolución de los procesos?

OBJECTIVE: To evaluate the impact of an organisational change in the musculoskeletal referral pathway in our health management area (HMA) by identifying changes in the ability to improve healthcare outcomes by facilitating referral to the most suitable specialty. DESIGN: This prospective descriptive study aimed to evaluate referral trends from primary care services (PCS) and hospital care (PHS) to musculoskeletal services from 2012 to 2018. MATERIALS AND METHODS: We included all patients who were referred to any of the 3 musculoskeletal services from our HMA catchment area, without specifying sample size. The variables studied were PCS, PHS, service of origin and destination. We used the SPSS programme for the statistical analysis and obtained absolute frequency data. RESULTS: The total number of referrals from PCS increased from 25,575 in 2012 to 24,871 in 2018. PHS referrals decreased from 17,207 in 2012 to 9,803 in 2018. With regards to PCS referrals, the service most increasing the number of referrals to the musculoskeletal team was the Rehabilitation Service, from 8.2% in 2012 to 47% in 2018. Regarding PHSs referrals by specialty, the service that most reduced the number of referrals to the musculoskeletal team was the Traumatology Service, from 10,587 in 2012 to 3,911 in 2018. CONCLUSIONS: The redesign of the musculoskeletal referral pathway improved healthcare outcomes by improving the quality of the referral process. In this organisational change, the Rehabilitation Service took the leadership from the point of view of healthcare and management of the musculoskeletal process, collaborating in the improvement of the healthcare outcomes of these processes.

Role of HLA-DRB1*04 in the susceptibility and HLA-DRB1*08 in the protection for development of rheumatoid arthritis in a population of Southern Mexico: brief report.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease with an increased prevalence in Mexico. Although its etiology is unknown, its development can be influenced by environmental factors such as smoking and viral infections. But among the factors influencing susceptibility, it is the genetic factors that predominate, mainly the HLA-DRB1 genes, and specifically the alleles that have the shared epitope (SE). A transversal study was performed, in which 31 patients (28 women and 3 men) with RA, treated at the autoimmunity clinic of the High Specialty Hospital Ciudad Salud in Tapachula, Chiapas, southern México, were enrolled. Clinical, biochemical, and demographic data were analyzed; ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), RF (rheumatoid factor), and ACPA (anticitrullinated peptide antibody) were recorded. All patients had at least one positive RA biological marker. For HLA alleles frequencies comparison, we enrolled ethnically matched healthy controls in a ratio of 3:1 for 25 cases and 4:1 for 6 cases in order to guarantee the balance between groups regarding the mean of age and proportion of gender (males vs females). HLA-DRB1*04 was found to be significantly increased in patients compared with ethnically matched healthy controls (p 0.0007, OR: 2.8, 95% CI 1.5-5.1); contrarily, DRB1*08 showed a protective effect (p 0.005, OR 0.1). This paper confirmed the involvement of HLA genes on risk determination for RA in a population of Mexican Mestizos from Tapachula, Chiapas. Key Points • HLA-DRB1*04 confirms the increased risk of rheumatoid arthritis. • HLA-DRB1*08 showed a more definite protective effect in southern Mexicans mestizos, a population with more Amerindian ancestry.

Local coordination of Fe(3+) in layered LiCo(1-y)Al(y)O(2) oxides determined by high-frequency electron paramagnetic resonance spectroscopy.

The local coordination of Fe(3+) spin probes in trigonal LiAl(y)Co(1-y)O(2) was studied using high-frequency electron paramagnetic resonance spectroscopy. This technique allows the determination of Fe(3+) ions in respect to axial and rhombic zero-field splitting parameters (ZFS). After the progressive replacement of Co by Al, the axial D parameter of Fe(3+) increases from +0.0548 to +0.2802 cm(-1). On the same order, the rhombic E parameter decreases. Structural information about the Fe(3+) site in layered LiAl(y)Co(1-y)O(2) oxides was based on modeling of the magnitude of the ZFS parameters by means of the Newman superposition model. It was found that the first metal coordination sphere including Co(3+) and Al(3+) ions gave rise to differentiation of the Fe(3+) dopants in respect to local trigonal and rhombic distortion. The maximum trigonal distortion for the FeO(6) octahedron was achieved when Fe(3+) spin probes were surrounded by Al only, while the Co environment yields a rhombic distortion of the FeO(6) octahedron.

[Analysis of the frequency of polytraumatized patients in motorcycle accidents in the pediatric publication attended in the Pediatric Hospital of Sinaloa between the years 2015 and 2017]. / Análisis de la frecuencia de pacientes politraumatizados en accidentes en motocicleta en la población pediátrica atendida en el Hospital Pediátrico de Sinaloa entre los años 2015 y 2017.

OBJECTIVES: Determine the frequency of polytraumatized pediatric patients involved in motorcycle accidents treated at the Pediatric Hospital of Sinaloa between 2015 and 2017, as well as to determine the frequency of traumatic brain injuries, thoracic, abdominal, limb injuries, days of hospital stay and mortality. MATERIAL AND METHODS: The selected population were patients under 18 years of age who were involved in motorcycle accidents treated at the Pediatric Hospital of Sinaloa in a period between January 1st, 2015 and December 31, 2017. RESULTS: The most affected gender was the male with the most frequent age of 14 years, accidents occurred more frequently on Fridays and Saturdays at night. July was the month with the highest frequency of accidents. The number of accidents increased every year. Most of the injured were passengers, 98.4% did not use safety equipment, the most frequent injury was head injury, followed by injuries in lower extremities, upper chest trauma and less frequent abdominal traumatism. DISCUSSION: There is a progressive increase in motorcycle accidents where the pediatric population is involved, the use of helmet is almost zero, most of the patients presented with head trauma, this study serves to see the current situation, as well as being the basis for Subsequent studies and conduct more campaigns for the prevention of motorcycle accidents and encourage the use of helmet in pediatric patients.

OBJETIVOS: Determinar la frecuencia de los pacientes pediátricos politraumatizados involucrados en accidentes por motocicleta atendidos en el Hospital Pediátrico de Sinaloa entre los años 2015 y 2017, así como determinar la frecuencia de traumatismos craneoencefálicos, lesiones torácicas, abdominales, en extremidades, días de estancia hospitalaria y mortalidad. MATERIAL Y MÉTODOS: La población seleccionada fueron pacientes menores de 18 años de edad que se encontraron involucrados en accidentes de motocicleta atendidos en el Hospital Pediátrico de Sinaloa en un período comprendido entre el 1o de Enero de 2015 al 31 de Diciembre de 2017. RESULTADOS: El género más afectado fue el masculino, con edad más frecuente de 14 años, los accidentes ocurrieron con mayor frecuencia los Viernes y Sábados en horario nocturno. Julio fue el mes con mayor índice de accidentes. La cantidad de accidentes se incrementó cada año. La mayoría de los lesionados fueron pasajeros, 98.4% no utilizó equipo de seguridad, la lesión más común fue el traumatismo craneoencefálico, seguido de lesiones en extremidades inferiores, superiores, traumatismo torácico y la menos común, el traumatismo abdominal. DISCUSIÓN: Hay un incremento progresivo en los accidentes en motocicleta donde se involucra la población pediátrica, el uso de casco es casi nulo, la mayoría de los pacientes presentó traumatismo craneoencefálico, este estudio sirve para analizar el panorama actual, así como ser la base de estudios posteriores y realizar más campañas para la prevención de accidentes en motocicleta y fomentar el uso de casco en pacientes pediátricos.

Effects of an Exoskeleton-Assisted Gait Motor Imagery Training in Functional Brain Connectivity.

Lower-limb exoskeletons have been used in gait rehabilitation to facilitate the restoration of motor skills. These robotics systems could be complemented by Brain-Computer Interfaces (BCIs) to assist or rehabilitate people with walking disabilities. In this preliminary study, electroencephalography-based brain functional connectivity is analyzed during exoskeleton-assisted gait motor imagery (MI) training. Partial Directed Coherence (PDC) analysis was employed to assess the exchange of information flow between EEG signals during gait MI in four healthy subjects, two using an exoskeleton and two without using it. Besides, in order to explore the functional connectivity, an outflow index based on the number of significant directed connectivities revealed by the PDC analysis is proposed. We found that the outflow index increases in the central zone (C2, C3, C4) while decreases in the central-parietal (CP1, CP2) and fronto-central (FC1) zones when the training was assisted by an exoskeleton. The results obtained can be useful to obtain informative features for BCI applications as well as in motor rehabilitation.