Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.

BACKGROUND: Inborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken. OBJECTIVES: To estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness. METHODS: For this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction. RESULTS: Of the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases. CONCLUSION: Children with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).

Family-base rare variant association analysis in Saudi Arabian hydrocephalus subjects using whole exome sequencing.

BACKGROUND: Hydrocephalus is a highly heterogeneous multifactorial disease that arises from genetic and environmental factors. Familial genetic studies of hydrocephalus have elucidated four robustly associated hydrocephalus associated loci. This study aims to identify potential genetic causation in cases of hydrocephalus, with or without spina bifida and Dandy Walker Syndrome (DWS), using family-based rare variant association analysis of whole exome sequencing. METHODS: We performed whole exome sequencing in 143 individuals across 48 families where at least one offspring was affected with hydrocephalus (N.=27), with hydrocephalus with spina bifida (N.=21) and with DWS (N.=3), using Illumina HiSeq 2500 instrument. RESULTS: No pathogenic or putative pathogenic single-nucleotide variants were evident in the four known hydrocephalus loci in our subjects. However, after examining 73 known hydrocephalus genes previously identified from literature, we identified three potentially impactful variants from the cohort. Using a gene panel comprising variants in known neural tube defects loci, we identified a total of 1024 potentially deleterious variants, of which 797 were missense variants and 191 were frameshift variants, 36 were stop gain/loss variants. A small portion of our family pedigree analyses yielded putative genetic signals which may be responsible for hydrocephaly elated phenotypes, however the low diagnostic yield may be due to lack of capture of genetic variants in the exonic regions i.e. structural variants may only be evident from whole genome sequencing. CONCLUSIONS: We identified three potentially impactful variants from our cohort in 73 known hydrocephalus genes previously identified in literature.

SAA-UNet: Spatial Attention and Attention Gate UNet for COVID-19 Pneumonia Segmentation from Computed Tomography.

The disaster of the COVID-19 pandemic has claimed numerous lives and wreaked havoc on the entire world due to its transmissible nature. One of the complications of COVID-19 is pneumonia. Different radiography methods, particularly computed tomography (CT), have shown outstanding performance in effectively diagnosing pneumonia. In this paper, we propose a spatial attention and attention gate UNet model (SAA-UNet) inspired by spatial attention UNet (SA-UNet) and attention UNet (Att-UNet) to deal with the problem of infection segmentation in the lungs. The proposed method was applied to the MedSeg, Radiopaedia 9P, combination of MedSeg and Radiopaedia 9P, and Zenodo 20P datasets. The proposed method showed good infection segmentation results (two classes: infection and background) with an average Dice similarity coefficient of 0.85, 0.94, 0.91, and 0.93 and a mean intersection over union (IOU) of 0.78, 0.90, 0.86, and 0.87, respectively, on the four datasets mentioned above. Moreover, it also performed well in multi-class segmentation with average Dice similarity coefficients of 0.693, 0.89, 0.87, and 0.93 and IOU scores of 0.68, 0.87, 0.78, and 0.89 on the four datasets, respectively. Classification accuracies of more than 97% were achieved for all four datasets. The F1-scores for the MedSeg, Radiopaedia P9, combination of MedSeg and Radiopaedia P9, and Zenodo 20P datasets were 0.865, 0.943, 0.917, and 0.926, respectively, for the binary classification. For multi-class classification, accuracies of more than 96% were achieved on all four datasets. The experimental results showed that the framework proposed can effectively and efficiently segment COVID-19 infection on CT images with different contrast and utilize this to aid in diagnosing and treating pneumonia caused by COVID-19.

Thyroid Disorders Spectrum in Pediatric Endocrine Clinic; Seven-Year Experience of a Teaching Hospital in Saudi Arabia.

Thyroid disorders constitute one of the major endocrine disorders in pediatric service. It includes a range of congenital versus acquired anatomic and/or functional thyroid diseases in growing children that has a spectrum of severity from severe intellectual disability effect to subclinical mild pathologies. This study was designed to analyze the demographic characteristics, clinical pattern, and severity of thyroid disorders in the pediatric endocrine clinic patients at the teaching hospital of the university over a 7-year duration. A total number of 148 patients with thyroid disorders were seen in pediatric Endocrine clinic during the time between January 2015 and December 2021. Female patients constitute 64% of them. Acquired Hypothyroidism was the commonest disorder; 34% of the cases followed by the congenital hypothyroidism (CH), then Hashimoto's thyroiditis, and 5.8% for others. While a very small percentage was acquired hyperthyroidism. The majority of referrals were from dermatology and other service for the screening of thyroid disease as association with other autoimmune diseases with percentage of 28.3%. Next was neck swelling manifestation in 22.6%. Thyroid disorders in children, both congenital and acquired, constitute an important medical issue for pediatricians to be aware of its variable presentations, and its potential serious health consequences on the affected children if not diagnosed and treated earlier. Acquired hypothyroidism constitutes more percentage of the thyroid disorders followed in the pediatric endocrinology outpatient clinics. Congenital hypothyroidism is the second most common thyroid disorder in the outpatient unit, having the most potential complications. These results support the international studies with the female predominance in most of thyroid disorders.

Intussusception and COVID-19 in Children: A Systematic Review and Meta-Analysis.

Background: Intussusception (ISN) post-COVID-19 infection in children is rare but can occur. SARS-CoV-2 may play a role in the pathogenesis of ISN and trigger immune activation and mesenteric adenitis, which predispose peristaltic activity to "telescope" a proximal bowel segment into the distal bowel lumen. Objectives: To estimate the prevalence of SARS-CoV-2 infection in ISN children and analyze the demographic parameters, clinical characteristics and treatment outcomes in ISN pediatric patients with COVID-19 illness. Methods: We performed this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies reporting on the incidence of ISN post-SARS-CoV-2 infection in children, published from 1 December 2019 until 1 October 2022, in PROQUEST, MEDLINE, EMBASE, PUBMED, CINAHL, WILEY ONLINE LIBRARY, SCOPUS and NATURE, with a restriction to articles available in the English language, were included. Results: Of the 169 papers that were identified, 34 articles were included in the systematic review and meta-analysis (28 case report, 5 cohort and 1 case-series studies). Studies involving 64 ISN patients with confirmed COVID-19 (all patients were children) were analyzed. The overall pooled proportions of the ISN patients who had PCR-confirmed SARS-CoV-2 infection was 0.06% (95% CI 0.03 to 0.09, n = 1790, four studies, I2 0%, p = 0.64), while 0.07% (95% CI 0.03 to 0.12, n = 1552, three studies, I2 0%, p = 0.47) had success to ISN pneumatic, hydrostatic and surgical reduction treatment and 0.04% (95% CI 0.00 to 0.09, n = 923, two studies, I2 0%, p = 0.97) had failure to ISN pneumatic, hydrostatic and surgical reduction treatment. The median patient age ranged from 1 to 132 months across studies, and most of the patients were in the 1−12 month age group (n = 32, 50%), p = 0.001. The majority of the patients were male (n = 41, 64.1%, p = 0.000) and belonged to White (Caucasian) (n = 25, 39.1%), Hispanic (n = 13, 20.3%) and Asian (n = 5, 7.8%) ethnicity, p = 0.000. The reported ISN classifications by location were mostly ileocolic (n = 35, 54.7%), and few children experienced ileo-ileal ISN (n = 4, 6.2%), p = 0.001. The most common symptoms from ISN were vomiting (n = 36, 56.2%), abdominal pain (n = 29, 45.3%), red currant jelly stools (n = 25, 39.1%) and blood in stool (n = 15, 23.4%). Half of the patients never had any medical comorbidities (n = 32, 50%), p = 0.036. The approaches and treatments commonly used to manage ISN included surgical reduction of the ISN (n = 17, 26.6%), pneumatic reduction of the ISN (n = 13, 20.2%), antibiotics (n = 12, 18.7%), hydrostatic reduction of the ISN (n = 11, 17.2%), laparotomy (n = 10, 15.6%), intravenous fluids (n = 8, 12.5%) and surgical resection (n = 5, 7.8%), p = 0.051. ISN was recurrent in two cases only (n = 2, 3.1%). The patients experienced failure to pneumatic (n = 7, 10.9%), hydrostatic (n = 6, 9.4%) and surgical (n = 1, 1.5%) ISN treatment, p = 0.002. The odds ratios of death were significantly higher in patients with a female gender (OR 1.13, 95% CI 0.31−0.79, p = 0.045), Asian ethnicity (OR 0.38, 95% CI 0.28−0.48, p < 0.001), failure to pneumatic or surgical ISN reduction treatment (OR 0.11, 95% CI 0.05−0.21, p = 0.036), admission to ICU (OR 0.71, 95% CI 0.83−1.18, p = 0.03), intubation and placement of mechanical ventilation (OR 0.68, 95% CI 0.51−1.41, p = 0.01) or suffering from ARDS (OR 0.88, 95% CI 0.93−1.88, p = 0.01) compared to those who survived. Conclusion: Children with SARS-CoV-2 infection are at low risk to develop ISN. A female gender, Asian ethnicity, failure to ISN reduction treatment (pneumatic or surgical), admission to ICU, mechanical ventilation and suffering from ARDS were significantly associated with death following ISN in pediatric COVID-19 patients.

Global Coinfections with Bacteria, Fungi, and Respiratory Viruses in Children with SARS-CoV-2: A Systematic Review and Meta-Analysis.

Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06−8.17, I2 = 0% versus 5.31%, 95% CI 4.31−6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45−2.99, I2 = 0% versus 0.62%, 95% CI 0.00−1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70−4.34, I2 = 0% versus 4.91%, 95% CI 3.97−5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

Characteristics of visits and predictors of admission from a paediatric emergency room in Saudi Arabia.

BACKGROUND: The Emergency Repartment (ER) is one of the most used areas in healthcare institutions. Problems with over utilisation and overcrowding have been reported worldwide. This study aims at examining the characteristics of paediatric ER visits, the rate of hospital admissions and its associated predictors at King Fahd Hospital of the University in the Eastern Province of Saudi Arabia. METHODS: This is a retrospective, medical record-based study. Variables included gender, age group, nationality, complaints, Triage level, shifts and seasons. Descriptive statistics were reported as frequencies/percentages. P-values were obtained through a Chi-Squared test while unadjusted and adjusted odds ratios were estimated by binary logistic regression, where admission was considered as the outcome. RESULTS: The total number of paediatric patients included was 46,374, and only 2.5% were admitted. Males comprised 55.4% while females comprised 44.6%. The most common age group were toddlers, and 92.4% of the total sample were Saudis. The most common complaint was fever (26.9%) followed by respiratory symptoms (24.9%). Only 7 patients (0.02%) were classified as triage I (Resuscitation), and most were triage IV (Less urgent) (71.0%). Most visits occurred during the winter months. Adjusted ORs showed that neonates had higher odds of admission (OR = 3.85, 95%CI = 2.57-5.76). Moreover, those presenting with haematological conditions showed an OR of 65.49 (95%CI = 47.85-89.64), followed by endocrine conditions showing an OR of 34.89 (95%CI = 23.65-51.47). Triage I had a very high odds of admission (OR = 19.02, 95%CI = 2.70-133.76), whereas triage V was associated with a very low odds of admission (OR = 0.30, 95%CI = 0.23-0.38). CONCLUSIONS: A low rate of hospital admission was found in comparison with other rates worldwide. This was mostly attributed to an alarmingly high number of non-urgent ER visits. This further emphasises the problem with improper use of ER services, as these cases should be more appropriately directed towards primary healthcare centres. Further studies to examine the impact of prioritising patients in the ER based on the identified predictors of hospital admission, in addition to the standard triage system, are suggested.

Next-generation UWB antennas gadgets for human health care using SAR.

The body area network is now the most challenging and most popular network for study and research. Communication about the body has undoubtedly taken its place due to a wide variety of applications in industry, health care, and everyday life in wireless network technologies. The body area network requires such smart antennas that can provide the best benefits and reduce interference with the same channel. The discovery of this type of antenna design is at the initiative of this research. In this work, to get a good variety, the emphasis is on examining different techniques. The ultra-wide band is designed, simulated, and manufactured because the ultra-wide band offers better performance compared to narrowband antennas. To analyze the specific absorption rate, we designed a multilayer model of human head and hand in the high-frequency structure simulator. In the final stage, we simulated our antennas designed with the head and hand model to calculate the results of the specific absorption rate. The analysis of the specific absorption rate for the head and hand was calculated by placing the antennas on the designed model.

A Comparative Systematic Literature Review on Knee Bone Reports from MRI, X-rays and CT Scans Using Deep Learning and Machine Learning Methodologies.

The purpose of this research was to provide a "systematic literature review" of knee bone reports that are obtained by MRI, CT scans, and X-rays by using deep learning and machine learning techniques by comparing different approaches-to perform a comprehensive study on the deep learning and machine learning methodologies to diagnose knee bone diseases by detecting symptoms from X-ray, CT scan, and MRI images. This study will help those researchers who want to conduct research in the knee bone field. A comparative systematic literature review was conducted for the accomplishment of our work. A total of 32 papers were reviewed in this research. Six papers consist of X-rays of knee bone with deep learning methodologies, five papers cover the MRI of knee bone using deep learning approaches, and another five papers cover CT scans of knee bone with deep learning techniques. Another 16 papers cover the machine learning techniques for evaluating CT scans, X-rays, and MRIs of knee bone. This research compares the deep learning methodologies for CT scan, MRI, and X-ray reports on knee bone, comparing the accuracy of each technique, which can be used for future development. In the future, this research will be enhanced by comparing X-ray, CT-scan, and MRI reports of knee bone with information retrieval and big data techniques. The results show that deep learning techniques are best for X-ray, MRI, and CT scan images of the knee bone to diagnose diseases.

A Proposed Maneuver to Guide Transseptal Puncture Using Real-Time Three-Dimensional Transesophageal Echocardiography: Pilot Study.

Aim of Study. To assess the feasibility of a new proposed maneuver "RATLe-90" using real-time three-dimensional transesophageal echocardiography (RT-3DTEE) for anatomically oriented visualization of the interatrial septum (IAS) in guiding the transseptal puncture TSP. Methods. The study included 20 patients (mean age, 60.2 ± 6.7 years; 60% males) who underwent TSP for different indications. RT-3DTEE was used to guide TSP. The proposed maneuver RATLe-90 (Rotate-Anticlockwise-Tilt-Left-90) was applied in all cases to have the anatomically oriented en face view of the IAS from the right atrial (RA) aspect. Having this anatomically oriented view, we guided the TSP catheter towards the proper puncture site according to the planned procedure. Results. Using the RATLe-90 maneuver, the anatomically oriented en face view of the IAS from the RA was obtained in all patients. We were able to guide the puncture catheter to the proper puncture site on the IAS. The 3D images obtained were clearly understood by both echocardiographers and interventionists. The RATLe-90 maneuver acquisition time was 19.9 ± 1.6 seconds. The time-to-tent was 64.8 ± 16.3 seconds. Less TEE probe manipulations were needed while guiding the TSP. Conclusions. Application of RT3D-TEE during TSP using RATLe-90 maneuver is feasible with shorter fluoroscopy time and minimizing TEE probe manipulations.

Real time three-dimensional transesophageal echocardiography guided coronary sinus cannulation during CARILLON mitral annuloplasty device therapy for a patient with chronic severe mitral regurgitation.

The coronary sinus (CS) has become a clinically important structure especially through its role in providing access for different cardiac procedures such as arrhythmia ablation, biventricular pacing and recently, percutaneous valvular interventions. Fluoroscopy with or without two-dimensional transesophageal echocardiography is the widely used method for guidance. A 78-year-old female patient undergoing percutaneous CARILLON mitral annuloplasty device therapy for chronic severe symptomatic mitral regurgitation. After insertion of the CS catheter through the right internal jugular vein, multiple trials for CS cannulation guided by fluoroscopy and two-dimensional transesophageal echocardiography were unsuccessful. So, real time three-dimensional zoom mode was used. Then, the volume was rotated to have the anatomically oriented enface view of the interatrial septum from the right atrial perspective. The CS ostium was identified adjacent to the eustachian valve. Then the catheter was reintroduced through the superior vena cava into the right atrium then easily navigated to cannulate the CS ostium. The position was confirmed by the fluoroscopically known course of the CS plus the pattern of the invasive pressure wave form. CS cannulation is not always feasible using fluoroscopy and/or two-dimensional Echocardiography guidance. Real time three-dimensional transesophageal echocardiography can be used to guide CS cannulation as it provides an anatomically oriented and informative enface view of the CS ostium. It can help reducing fluoroscopic radiation time.

Efficacy of Lepidium sativum against carbon tetra chloride induced hepatotoxicity and determination of its bioactive compounds by GCâ¿¿MS.

Lepidium sativum seed (LSS) (family: Cruciferae) has been used in traditional medicine for the treatment of jaundice, liver problems, spleen diseases and gastrointestinal disorders. It was also reported to possess antihypertensive, diuretic, anti-asthmatic, antioxidant, and anti-inflammatory activities. Attempt has been made to study hepatoprotective potential of LSS available in Saudi Arabian Market. The aim of the present study was to determine the hepatoprotective effect of ethanolic extracts of LSS against carbon tetrachloride (CCl4) induced acute liver injury in rats. The bioactive compounds responsible for this activity have been analyzed by GCâ¿¿MS. To evaluate the hepatoprotective activity, six groups (n = 6) of rats were taken. First group was control, second was toxic and other groups received oral test solutions: 100 mg/kg silymarin, or LSS (100, 200, and 400 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver tissues were collected for biochemical, antioxidant and microscopic analyses. The bioactive constituents present in the extract were analyzed by GCâ¿¿MS. Results showed that pretreatment with LSS and silymarin significantly reduced the level of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin (BIL), which was increased significantly in toxic group treated with only CCl4. Histological analysis of liver tissues in groups pretreated with LSS and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the toxic group. GCâ¿¿MS analysis of LSS showed the presence of twelve major fatty acids including alpha-linolenic acid as a major constituent. These results indicated that LSS exerts enhance hepatoprotective activity that could be attributed towards its antioxidant activity, coupled together with the presence of anti-inflammatory compounds in LSS extract.