A document by Riska Wahyuningtyas. Click on the document to view its contents.

This is an invited commentary on robotic reoperative surgery without cardioplegia. Tips and shortfalls are discussed.

Abstract The coronavirus disease (COVID-19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella-like eruption, representing an additional effect of the SARS-CoV-2 infection, as commonly observed in other viral diseases. Considering that symptomatic COVID-19 patients generally undergo multi-drug treatments, the occurrence of a possible adverse drug reaction (ADR) presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59-year-old Caucasian woman, affected by a stable form of Chronic lymphocytic leukaemia, and symptomatic SARS-CoV.2 infection, treated with a combination of hydroxychloroquine sulphate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high-flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin and received a high-dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID-19 disease-related cutaneous manifestations, where is justified to continue the multi-drug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start an appropriate treatment.

Capture of cashew allergen by skin dendritic cells is enhanced in cashew-sensitized mice following epicutaneous delivery Running title: Sensitization to cashew leads to increased epicutaneous delivery of cashew allergenPierre-Louis Hervé1*, Benjamin Pelletier1, Noémie Assoun1, Nathalie Oreal1, Audrey Perrin1, Jean-Louis Labernardière1, Hugh A Sampson2* Correspondence should be addressed to P-L.H. (pierre-louis.herve@dbv-technologies.com; +33 1 84 86 11 30)1 DBV Technologies, 177-181 avenue Pierre Brossolette, 92120 Montrouge, France2 DBV Technologies, 12 East 49th Street Tower 49, Suite 4001, New York, NY 10017, USAMain text word count: 595

Fatigue experiments and numerical simulations based on the Linear Elastic Fracture Mechanics (LEFM) theory were conducted on the Even-Matched (EM) and Under-Matched (UM) 10CrNi3MoV Load-carrying Cruciform Welded Joints (LCWJs). The study firstly experimentally investigated the Fatigue Crack Growth Rate (FCGR) of base metal, EM, and UM weldments. The corresponding Paris parameters as essential input data are provided to assess the fatigue crack propagation behavior for weld toe and weld root failure. On the one hand, the Stress Intensity Factors (SIFs) at weld toe and weld root were calculated considering the effects of LCWJ specimen geometries, initial crack types, and sizes. The comparisons between simulated results and standards analytical solutions were executed, which exhibit good accordance. It proved that the fatigue fracture simulation procedure based on LEFM is appropriate for the fatigue assessment of LCWJs. Eventually, it conducted the parametric analysis by predicted S-N curves, which included in the weld length, initial crack shape, initial crack size, penetration length, and materials fracture parameter, to explore some safety assessment reference lines for both failure modes of LCWJ.

The use of genomic and phenotypic data to scan for outliers is a mainstay for studies of hybridization and speciation. Geographic cline analysis of natural hybrid zones is widely used to identify putative signatures of selection by detecting deviations from baseline patterns of introgression. As with other outlier-based approaches, demographic histories can make neutral regions appear to be under selection and vice versa. In this study, we use a forward-time individual-based simulation approach to evaluate the robustness of geographic cline analysis under different evolutionary scenarios. We measured the effects of drift on genetic differentiation, and on false positive and false negatives detection using geographic clines. We modeled multiple stepping stone hybrid zones with distinct age, deme sizes, and migration rates, and evolving under different types of selection. We found that in young hybrid zones, drift increases overall genomic divergence, distorts cline shapes and increases both false positive and false negative rates. In old hybrid zones, genomic divergence and cline distortion are higher. Our results suggest that geographic clines are most useful for outlier analysis in young hybrid zones with large populations of hybrid individuals.

Introduction: For some patients whose LIMA cannot be used, surgeons have to choose other conduit materials to revascularize the LAD. This study was to explore the differences between SVG and LIMA used for LAD in terms of parameters measured by transit-time flow measurement (TTFM) and the early graft patency. Methods: A total of 374 patients who underwent CABG were included in this study. According to the strategy of the left descending artery (LAD) revascularization, 374 patients were assigned to two groups: a left internal mammal artery (LIMA)group(n=332) and a great saphenous vein (SVG) group (n=42). Results: Before propensity Score-Matched, compared with the LIMA-LAD group, the SVG-LAD group had a significantly higher MGF(37.85±23.28 vs 29.70±20.97ml/min, P=0.021),but a lower PI value (2.12±0.68 vs 2.65±1.01,P＜0.001).There was no significant difference between the two groups in terms of DF(P＞0.05). After 1:2 propensity Score-Matched, there were 114 patients were included (SVG-LAD 38, LIMA-LAD 76), there was no difference in the baseline data between the two groups. Compared with the LIMA-LAD group, the SVG-LAD group also had a lower PI value (2.07±0.63 vs 2.74±1.02,P＜0.001),and also a higher MGF(37.27±24.31 vs 29.92±21.92ml/min),but there was no statistically difference(P=0.109). There was no significant difference between the two groups in DF (P＞0.05). There was no difference among the two groups in patency rate(P=0.405). Conclusion: SVG-LAD has a higher MGF and a lower PI value than LIMA-LAD before PSM but just has a lower PI value than LIMA-LAD after PSM. There was no difference among the two groups in early patency rate.

The Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve that is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is high in protein, amino acids, and microelements. In China, C. fluminea plays an important role in the diversity of freshwater ecosystems. The genome of C. fluminea has not yet been characterized, therefore, genome-assisted breeding and improvements cannot yet be implemented. In this work, we present a de novo chromosome-scale genome assembly of C. fluminea using PacBio and Hi-C sequencing technologies. The assembled genome comprised 4,728 contigs, with a contig N50 of 521.06 Kb, and 1,215 scaffolds with a scaffold N50 of 70.62 Mb. More than 1.51 Gb (99.17%) of genomic sequences were anchored to 18 chromosomes, of which 1.40 Gb (92.81%) of genomic sequences were ordered and oriented. The genome contains 38,841 coding genes, 32,591 (83.91%) of which were annotated in at least one functional database. Compared with related species, C. fluminea had 851 expanded gene families and 191 contracted gene families. The expanded genes were significantly enriched in 9 terms associated with metabolite synthesis. The phylogenetic tree showed that C. fluminea diverged from the ancestors of marine bivalves ~492.00 million years ago (Mya). Additionally, we identified two MITF genes in C. fluminea and several core genes involved in vitamin B6 metabolic pathways. The high-quality and chromosomal Asian Clam genome will be a valuable resource for a range of development and breeding studies of C. fluminea in future research.

Anthropogenically-driven climate warming is a hypothesized driver of animal body size reductions. Less understood are effects of other human-caused disturbances on body size, such as urbanization. We compiled 140,499 body size records of over 100 North American mammals to test how climate and urbanization, and their interactions with species traits, impact body size. We tested three hypotheses of body size change across urbanization gradients; urban heat island effects, fragmentation, and resource availability. Our results unexpectedly demonstrate urbanization is more tightly linked with body size changes than temperature, most often leading to larger individuals, thus supporting the resource availability hypothesis. In addition, life history traits, such as thermal buffering, activity time, and average body size play critical roles in mediating the effects of both climate and urbanization on intraspecific body size trends. This work highlights the value of using digitized, natural history data to track how human disturbance drives morphological change.

Background The ductus arteriosus, an essential fetal structure, normally closes spontaneously soon after birth. It’s persistence into late adulthood is considered rare; infective endarteritis complicating a patent ductus arteriosus (PDA) is an even rarer event. The clinical picture of an infected PDA could be subtle, and the diagnosis is frequently delayed. Case presentation We present the case of a young women who presented with prolonged fever, in whom we made the diagnosis of a patent ductus arteriosus complicated by infective endarteritis with vegetations in both pulmonary and aortic wall with mycotic aneurysms of the descending aorta. She underwent surgery and postoperative course was uneventful. Conclusion To our knowledge, this is the first reported case of a patent ductus arteriosus complicated with both pulmonary and aortic endarteritis.

Abstract Objective: This study aims to evaluate clinical and radiological findings and treatment outcomes of the patients with PIBO. Methods: One hundred fourteen children were enrolled. Initial demographic and clinical findings were evaluated. Pre- and post-treatment symptoms, radiological findings and scores, the number of admissions to the hospital and PICU were compared. Results: Seventy-three patients were male. The median age of the patients at initial pulmonary injury was 7.2 months, the median age at diagnosis was 17.5 months and the median interval from initial injury to diagnosis was 8.5 months. Thirty-five patients had mechanical ventilation history. Persistent wheezing was the most common complaints. The most common radiological findings were peribronchial thickening and air-trapping. Sixty-eight patients were treated with inhaled corticosteroid (IC), systemic corticosteroid (SC) and azithromycin (AZT) combination. 25 patients were treated with only IC, 14 with IC and AZT, and 7 with IC and SC. 82,5% of patients had clinical improvement. Chronic respiratory failure occurred in 11 patients, and three patients died. Bronchiectasis, atelectasis, hyperinflation and air trapping in HRCT improved significantly. Bhalla scores decreased from 8.3 to 6.5 (p= 0,001). IC, SC and AZT combination was effective than the other treatments. Conclusions: This study is one of the largest studies in the literature and one of the few studies that evaluate clinical and radiological outcomes. We found that IC, AZT and SC combination is clinically and radiologically effective in patients with PIBO.

Plastic bronchitis is an uncommon condition with a poor prognosis characterized by an obstructive respiratory pattern due to airway blockage by the presence of bronchial casts. Therefore, it is important to include it in the differential diagnosis of respiratory distress, particularly in patients with underlying pathologies predisposing to this condition. The etiology is multifactorial, but typically occurs in children with congenital heart disease, particularly post‐Fontan procedure. The treatment is based on improving the underlying condition, which can be challenging in this type of patients.

ants share the phytobiome with other members of the ecological community by sharing their physiology. The phytobiome is a collective ecological entity that senses external and internal stimuli via its member’s sensing apparatus (senome). The activated senome generates intercellular, and intra- and inter-organismal signals that induce genetically and epigenetically dependent modifications of phytobiome member transcriptomes. Ultimately, these genetic modifications alter the phenotypes of the collective phytobiome members. Mycorrhiza, epiphytic fungi, and dodder can physically transfer signals between kin and non-kin plants. Phytobiome members can release infochemicals by themselves, or modify plant volatile emissions and root exudates to act as signals for plant–plant interactions. These signals can change plant physiology and induce holobiont updates in receiver plants via a facilitative or competitive mechanism. Receiver plants eavesdrop on phytobiome cues and signals to anticipate responses to unfolding challenges. An emerging body of information in plant–plant interactions through inter-kingdom communication can be exploited in integrated crop management under field conditions. However, a holistic view is crucial for the manipulation of complex systems, such as the phytobiome, to avoid potential butterfly effects.

Herbivore grazing is an important determinant of plant community assemblages. We used data from a multi-year experimental study in Northern Fennoscandia to analyze the effect of reindeer (Rangifer tarandus) grazing on plant community diversity including its phylogenetic structure. Similar to previous studies on low productivity ecosystems in this region, we found no effect of grazing on plant biodiversity and a transition from dwarf shrubs to graminoids with pulse (i.e. grazed every other year) and press (i.e. grazed every year) grazing. Interestingly, communities with pulse grazing were more phylogenetically dispersed than communities with press grazing and lightly grazed communities. We argue that the indirect effects of reindeer grazing (e.g. interspecific competition and soil nutrient availability) may work in opposition of the direct effects (i.e. physical removal of species) and that the phylogenetic structure of the resulting community will depend upon the relative strengths of the direct and indirect effects. This interpretation suggests that the indirect effects of reindeer grazing in our study region are more important than the direct effects in driving community assembly for plant communities that are exposed to pulse grazing. Our results have important implications for the management of reindeer in Fennoscandia if pulses of grazing can increase the phylogenetic diversity of plant communities.

A rapid biodiversity assessment of insects and associated Laboulbeniales fungi was conducted over the course of five nights in August, 2018 at two central Florida lakes: Lake Eustis and the nearby protected and restored National Natural Landmark, Emeralda Marsh Conservation Area (EMCA), which encompasses a portion of Lake Griffin. These locations were selected because Lake Eustis was surveyed for Laboulbeniales in 1897 by mycologist Dr. Roland Thaxter, but has not since been investigated. Because Lake Eustis has been urbanized, with the lake perimeter almost entirely altered by human development, the site offers a look into Laboulbeniales diversity across a 121 year timeline, before and after human development. By surveying Lake Eustis and EMCA, a modern case study comparison of Laboulbeniales and insect diversity between a developed and unrestored system and a protected and restored system is made. A total of 4,022 insects were collected during the rapid assessment. Overall, insect abundance was greater at EMCA, with 3,001 insects collected, compared to 1,021 insects collected from Eustis. Though family level insect richness was comparable between sites, with 55 families present at EMCA and 56 at Eustis, 529 out of 3,001 (17.6%) of the insects collected at EMCA were hosts to parasitic Laboulbeniales fungi whereas only 2 out of 1,021 (0.19%) collected from Eustis were infected. There were 16 species of Laboulbeniales found at EMCA compared to only one at Eustis. The current number of Laboulbeniales species documented at Eustis was incredibly depauperate compared to the 27 species recorded by Thaxter in 1897, suggesting the possibility of utilizing Laboulbeniales as indicators of ecosystem health. A figure displaying host-parasite records and a species list of Laboulbeniales fungi is compiled and updated occurrence records for species of Ceratomyces and Hydrophilomyces are provided.

Potassium (K+) is a macronutrient for plant growth and development. Although a number of K-transporters are encoded in various plant genomes, functional characterization of these transport genes have lagged behind of genomic information in crop plants. In rice genome, a large expansion of high-affinity K-transporters (HAKs/KUPs/KTs) has been identified as compared to those in Arabidopsis genome suggesting a functional diversity of these transporters in cereals. We report here the functional characterization of a HAK member, OsHAK3, in rice using CRISPR-assisted genetic analysis. Expression of OsHAK3 was mainly found in roots and its protein was targeted to the plasma membrane. Loss of function of OsHAK3 led to a reduction of K+ uptake rate and K+ content, consistent with the finding that mutant plants became stunted under low-K+ conditions. In addition, the growth of Oshak3 mutants was more sensitive to salt stress due to altered K/Na ratio in the plants. Together, our data demonstrate that OsHAK3 plays a crucial role in K+ homeostasis, especially under K+-limited conditions and when plants face salinity stress.

The range of the Canada lynx (Lynx canadensis) has contracted substantially from its historical range prior to the 19th century. Using harvest records, we found that the southern range of the lynx in Ontario in the late 1940s collapsed and then in a short period of time increased to its largest extent in the mid-1960s where the lynx range spread south of the boreal forest for a decade. After this expansion the southern range contracted northwards beginning in the 1970s. Most recently, there has been a slight expansion between 2010-2017. We have attributed these dynamics on the southern range periphery to the fluctuation of the boreal lynx population in the core of the species’ range. In addition, connectivity to boreal lynx populations and snow depth seemed to condition whether the lynx expanded into an area. However, we did not find any evidence that would suggest that these changes were due to anthropogenic disturbances or competition. The boreal lynx population does not reach numbers as it once did, consequently we likely will not see large expansions of the southern lynx range as in the mid-1960s. Our results suggest that southern lynx range in Ontario have been driven by the magnitude of the boreal lynx population cycle, connectivity to the boreal forest and snow conditions. Therefore, it is quite unlikely that southern lynx population in the Great Lakes will ever recover, since the warming climate and forestry practices are causing a northward contraction of the boreal forest and likely with it the core lynx populations.

The multiaxial fatigue character of high-speed railway brake disc thermomechanical damage is studied in this work. Although the amplitude and distribution of temperature, strain and stress are similar with uniform and rotation loading methods, the multiaxial behavior and out-of-phase failure status can only be revealed by the latter one. With the help of a multiaxial fatigue model, fatigue damage evaluation and fatigue life prediction are implemented, the contribution of uniaxial fatigue parameter, multiaxial fatigue parameter and out-of-phase failure parameter to the total damage is discussed, the damage will be underestimated without the consideration of multiaxial characters and out-of-phase failure status. It can be announced that brake disc fatigue belongs to the type of multiaxial thermomechanical fatigue. The results of this work can help to understand the damage mechanism of high-speed railway brake disc, and provide theoretical foundation for design optimization from the perspective of multiaxial thermomechanical fatigue resistance.

Rationale, aims and objectives Discharging low-risk pregnant women is not usually contemplated in any procedure and obstetricians are therefore fully responsible for making this decision. Thus, a protocol establishing the procedures, tasks, aims, and activities of each healthcare professional involved in such cases would allow to streamline the process of admission and discharge of low-risk pregnant women with a normal pregnancy. The aim of this study was to establish the effectiveness and safety of a standardised assessment programme for the decision-making process of midwives in relation to the admission of pregnant women in a hospital emergency department. Method Retrospective observational cohort study evaluating the decision-making process of midwives when assessing pregnant women in an emergency department during the study period 2016-2017. The study population consisted of low- to moderate-risk pregnant women with a normal pregnancy who presented to the obstetric emergency unit (labour and delivery room) because of vaginal spotting, uterine contractions, bleeding, absence of foetal movements and/or suspected rupture of membranes. The primary study variable was the appropriateness of the decisions made by midwives (whether discharging or admitting pregnant women) in an obstetric emergency unit. Safety was assessed by the incidence of neonatal complications based on the Apgar test for women who had previously been discharged. Results The performance of the instrument used was found to be excellent as both the negative predictive value (appropriate discharge) and the positive predictive value (appropriate admission) were greater than 95%. In the safety evaluation, only one in every 200 newborns had an Apgar score at five minutes less than seven. Conclusions The adequacy of our standardised assessment programme has been found to be excellent, with an almost perfect performance based on the negative predictive value and appropriate safety margins based on the Apgar scores at birth obtained for previously discharged cases.

To the editor: Covid19 pandemic started in Dec 2019 and has affected >10 million people (1). Despite usage of personal protective equipment many healthcare workers (HCW) have been affected globally with Covid19 and some have died (2-4). We need a chemoprophylaxis drug which can stop viral replication and hydroxychloroquine (HCQ) has been shown to do that in-vitro (5). There have been few studies on usage of HCQ for treatment of covid19 with mixed results (6-7). HCQ for post-exposure prophylaxis (a 5-day course) in a randomised control trial showed no benefit (8). Indian council of medical research (ICMR) had recommended weekly prophylaxis (400 mg once a week) for all HCW in contact or looking after proven Covid19 cases (9). As per a recent report from India 4 or more weekly HCQ doses give better protection against Covid19 in HCW (10). However, questions have been raised about safety & efficacy of HCQ as a prophylaxis for Covid19. We did a survey across 11 hospitals in 7 cities in India about HCQ prophylaxis amongst HCW.A total of 301 HCW reported to be taking HCQ 400 mg once a week dose. Hospitals were located in big cities (Mumbai, Delhi, Kolkata, Hyderabad, Gurgaon, Jaipur, Bangalore) designated as Covid19 hotspots. Males were 186 and females were 115. Median age was 34 years (range 22-65 years). Doctors were 126, nurses were 169 and others were 6. All were working in hospitals treating Covid19 patients. Only 3 HCW stopped HCQ (1 due to headache and other 2 got bored). Median weekly doses taken were 9 (range 1-10). Nearly 50% (151/301) had taken HCQ weekly for 9 weeks. Side effects were seen in 17 people (nausea-7, gastritis-5, joint pain-1, sweating-1, constipation-1, vertigo-1 & headchae-1). ECG was not done and G6PD assay was also not done for anyone. From drug interaction point of view, 11 HCW were on additional drugs. Amlodipine and losartan were being taken by 5 people each, 3 were on metformin, 1 on insulin and 2 were on other drugs. Four (1.3%) developed Covid19 within 2 weeks of starting HCQ and all had mild disease (fever and mild cough) and recovered fully. None needed oxygen or intensive care.A total of 108 HCW were not taking HCQ working in the same hospitals. Median age was 32.5 years (range 23-64 years). Male to female ratio was 1:2. Doctors were 35, Nurses-66 and others-7. Amongst them 29 (27%) developed Covid19. All had mild symptoms but 2 needed oxygen and ICU stay. All recovered fully. So only 1.3% developed covid19 amongst HCW on HCQ prophylaxis vs. 27% in those not taking HCQ prophylaxis (p value <0.0001).In conclusion, its feasible to give safely weekly HCQ prophylaxis to HCW. It seems to effective but a survey is not the best scientific approach to prove efficacy. A randomised controlled trial is needed to confirm efficacy of weekly HCQ amongst HCW.Disclosure – All authors have nothing to declare.Contribution – All authors have contributed to this manuscript.Funding - Nil

Title: Implementation of early management of iron deficiency in pregnancy during the SARS-CoV-2 pandemicStewart T1, Lambourne J2, Thorpe-Jones D1, Thomas DW1.1University Hospitals Plymouth NHS Trust, Plymouth, Devon, PL6 8DH. 2East Kent Hospitals NHS Foundation Trust, William Harvey Hospital, Kennington Road, Willesborough, Ashford, Kent, TN24 0LZ

Exogenous progesterone is used to manage obstetric indications associated with reduced progesterone activity. This review examined evidence for oral natural micronised progesterone (NMP) and NMP-SR, a sustained-release formulation designed to overcome the limitations of conventional oral NMP. Oral NMP was effective for luteal phase support during assisted reproduction, and prevention of threatened spontaneous miscarriage and preterm delivery. NMP-SR was comparable to dydrogesterone for luteal phase support during assisted reproduction and maintenance of high-risk pregnancies. By releasing progesterone gradually and circumventing first-pass metabolism, NMP-SR elicits the desired therapeutic effect with added benefits of better bioavailability, once-daily dosing, and improved tolerability.

We conducted a study that aimed to shed light on the effects of COVID-19 on the emotional state of pregnant and postpartum women, which are specifically vulnerable groups. A cross-sectional study based on a web questionnaire for the assessment of general emotional stressor during the quarantine period of COVID-19, from April 20th till May 7th. Overall, 356 women of whom 251 pregnant and 101 post-partum filled the questionnaire. Among 251 pregnant women, 199 (79.3 %) reported moderate-high stress, 145 (57.8 %) high anxiety. A hundred and three (41.0%) reported a high level of depression (PH2>3). Among pregnant women, the following were the most prevalent stressors: fear that someone in their family will acquire the virus (80.1%), concern for the health of the baby (77.7%), fear that someone close will die from COVID-19 (72.9%) and worry of being infected within the hospital (71.7%). Univariate analysis of stress revealed that age (χ2=10.93, p<.004) and income level (χ2=13.35, p<.001) were associated with the level of stress. Stepwise logistic regression revealed that both age and income levels below the mean were predictors of stress. Among the 165 multiparous pregnant women, age (25-34 vs. 35-44) as a predictor of stress (p<.04). Our study clearly showed an enormous negative effect of the COVID-19 pandemic on the emotional condition of both pregnant and postpartum women. This provides an insight into the relation between economy and emotional state during the uncertainty period. This adds challenges to the healthcare system in providing means and solutions during disasters

Background – In case of breast abscess, many patients stop breastfeeding on the advice of a health professional. Purpose – We reviewed our experience of treatment of lactating breast abscesses by ultrasound-guided aspiration and suggest an algorithm of their management. We also analyzed the continuation of breastfeeding of these patients after advices from trained teams. Materiel and methods – We conducted a retrospective study from April 2016 to April 2017, including 34 patients referred for a breast abscess during lactation at the Duroc Breast Imaging Center. Results – A single aspiration was sufficient in 64.3% of cases. The delay between the occurrence of the abscess and the indication for drainage was significantly higher for patients who have needed finally surgical drainage (p = 0,0031). There were no difference of size of abscesses between patients receiving needle aspiration alone and those who have undergone surgery (p = 0,97). All patients who had been managed by needle aspiration continued breastfeeding after the treatment and 40% of the patients were still breastfeeding at 6 months. Conclusion - The management of lactating breast abscess by ultrasound-guided needle aspiration is an effective alternative to surgery. It appears to be effective regardless of the size of the abscess and is compatible with the continuation of breastfeeding. Our study has indeed shown that if they are well advised, the majority of patients continue breastfeeding so that it is essential that health professionals be better trained regarding the management of breastfeeding complication