[Respiratory complications of accidental drownings in children]. / Complications respiratoires des noyades accidentelles chez l'enfant.

Accidental drownings are severe and sometimes mortal events in children. Our study aims to better clarify the epidemiology and the respiratory complications of these accidents in our hospital. We led a retrospective study over 10 years concerning the children hospitalized for accidental drowning in our hospital centre. Age at the moment of the accident, sex, history of accident, hospitable care, thoracic imaging and neurological outcome of the children were studied. In total, 83 children were hospitalized (5 years on average, 70% being boys). The drowning especially took place in fresh water (71%), particularly in swimming pools (51.8%). Stages III and IV of drowning concerned 40.9% of the population. The coverage was the following one: admittance in ICU 57.8%, mechanical ventilation 34.9%, oxygen therapy 16.9%, antibiotics 87.9%. A normal chest x-ray was present in 45.7% of the cases. Drowning in fresh water, especially in contaminated fresh water (canal, WC, etc.), induced atelectasis (10.8%), whereas drowning in sea water induced diffuse infiltrates (8.4%). Aspiration pneumonia (33.7%) was present in both cases and a pulmonary oedema (6%) was only noticed during stage IV drowning. The secondary infections were rare (1 case was suspected and another probable). A child presented a secondary acute respiratory distress syndrome (1.2 %). Finally, 7 deaths (8.4%) and 1 case with severe neurological sequelae (1.2%) were noted. Accidental drowning causes important consequences in children. The long-term respiratory outcomes have not been properly studied. Prevention of such accidents is based on parental vigilance during their child's bathe.

[Extracorporeal assistance in paediatric intensive care]. / Assistance extracorporelle en réanimation pédiatrique.

OBJECTIVE: For 3 years we have used extracorporeal assistance in intensive care frequently. This study evaluates our results. METHOD: We studied the patient records for those treated between January 2002 and January 2005. The method used, indications and morbidity/mortality were analysed. RESULTS: We performed 24 circulatory assistance procedures in 20 patients (median age: 5 months), arterio-venous with oxygenation (n=18), veino-venous with oxygenation (n=3) or biventricular (n=3). The indications were post cardiotomy cardio-respiratory failure (Group I; n=20, 16 patients), pure respiratory failure (Group II: n=1), or pre-transplant/recovery (Group III: n=3). Five procedures (4 from group I and 1 from group III) required cardiac massage (no fatalities). The average duration of assistance was 7 +/- 6 days (2 to 20 days). Treatment was successfully discontinued in sixteen patients 80%), one of them thanks to heart transplant. Four (20%) died during assistance. The morbidity essentially consisted of further surgery for haemostasis, multiple transfusions, and infections. Three patients (15%) died later (1 at 17 months after discontinuation) from complications unrelated to the assistance. No neurological sequelae were noted in the survivors. CONCLUSION: These results confirm the usefulness of circulatory assistance when medical treatment has failed, particularly in the post-operative period of paediatric cardiac surgery or while awaiting transplantation.

[Postoperative hyponatremia in children: pathophysiology, diagnosis and treatment]. / Les hyponatrémies postopératoires de l'enfant: physiopathologie, diagnostic en traitement.

OBJECTIVES: To review the current data on pathophysiology, causes and management of postoperative hyponatremia in children. DATA SOURCES AND EXTRACTION: The Pubmed database was searched for articles, combined with references analysis of major articles on the field. DATA SYNTHESIS: The incidence of postoperative hyponatremia has been evaluated at 0.34% and its mortality significant. Postoperative hyponatremia is triggered by the diminished renal ability to excrete free water, due to antidiuretic hormone release. Inappropriate secretion of antidiuretic hormone is frequently seen after spine, cardiac and neurosurgery but can occur even after minor surgery. In this context, the infusion of hypotonic fluids represents a strong risk factor for developing hyponatremia. Other causes of hyponatremia are represented by extrarenal fluid losses, cerebral salt wasting syndrome, desalination phenomenon, adrenal insufficiency or some medications. Preventive treatment is essential and based on prohibition of hypotonic fluids infusion and the use of isotonic fluids infusions, maintenance of a normal total blood volume, the observance of the good practice recommendations for fluid infusion in children, and frequent blood and urine sodium concentration determinations in patients at risk for developing hyponatremia. Hyponatremic encephalopathy requires an emergent management, consisting in respiratory care and hypertonic sodium chloride infusion. Chronic hyponatremia is most often asymptomatic and the main neurological risk factor is represented by a too rapid correction of plasma sodium, which may lead to centropontine myelinolysis.

High plasma ropivacaine concentrations after fascia iliaca compartment block in children.

BACKGROUND: The pharmacokinetic profile of local anaesthetics is influenced by the mode of administration. We sought to compare the pharmacokinetics of two doses of ropivacaine after fascia iliaca compartment (FIC) block in children. METHODS: In this prospective, double-blind study, children received an FIC block as a part of their anaesthetic management during elective orthopaedic surgery on the thigh. They were randomized to receive ropivacaine 0.7 ml x kg(-1) using either a 0.375% or 0.5% solution. Venous blood samples were drawn up to 6 h after injection. Plasma concentrations of ropivacaine were measured by gas-liquid chromatography. RESULTS: Six children (10.2 (range 5-15) yr, 35.6 (sd 10) kg were included. FIC block provided satisfactory peroperative pain relief. No signs of toxicity were observed, but high maximal plasma concentrations (C(max) 4.33-5.6 microg ml(-1)), were observed for three of four patients in the ropivacaine 0.5% group. The two patients in the 0.375% group showed values within the safe range (C(max) 0.66 and 0.98 microg ml(-1) respectively). Even though no toxic effects were observed, these results led us to discontinue the study. CONCLUSIONS: The administration of ropivacaine 3.5 mg x kg(-1) can be associated with sustained high plasma concentrations of ropivacaine, outside the tolerable range. In view of these results, we recommend the use of lower ropivacaine dosage during FIC block in children.

[Shaken baby syndrome: improvement of cerebral blood flow velocity after a subdural external derivation in a six-month old infant]. / Le syndrome du bébé secoué: amélioration de la circulation cérébrale après dérivation sous-durale externe chez un nourrisson de six mois.

The shaken baby syndrome is a severe form of child abuse. The intracranial injuries are associated with a high morbidity and mortality rates. A 6 month-old healthy infant presented at home a cardiorespiratory arrest. After a cardiopulmonary resuscitation, radiological survey showed sub-dural haematomas and retinal haemorrhages, without a history of trauma. The diagnosis of shaken baby syndrome was made. Despite medical management and a fontanelle tap, clinical signs of intracranial hypertension worsened. Transcranial Doppler examination found the cerebral blood flow velocities to be decreased while the pulsatility index was increased. A sub-dural-external drainage allowed the cerebral blood flow to increase and the pulsatility index to decrease. We conclude that transcranial Doppler examination can be helpful for the clinician caring children presenting a shaken baby syndrome.

[Outcome of infants with hypoplastic left heart syndrome diagnosed in utero]. / Devenir des enfants atteints d'une hypoplasie du coeur gauche diagnostiquée in utero.

The authors report the results of prenatal diagnosis of the hypoplastic left heart syndrome since 1998 in the University Hospitals of Marseille and Montpellier. Twenty-four prenatal diagnoses of this condition were made in mothers with a mean age of 29 (18 to 40 years) and after a mean term of 22 (18.5 to 33) weeks of amenorrhea. Seventeen therapeutic abortions were carried out and 7 neonates born after a mean term of 39 (28 to 40) weeks, were admitted to the paediatric intensive care unit. Two patients required ventilatory assistance with one early death. The other patients were stable after surgery. A Norwood (first stage) procedure was carried out in 6 neonates at a mean age of 5 (1 to 6) days. There was only one survivor (17%). Prenatal diagnosis of the hypoplastic left heart syndrome allows cardiac and extracardiac evaluation of foetuses with this condition. Therapeutic abortions may be proposed and was the commonest choice of the parents in this study. On the other hand, despite better management of neonates with this prenatal diagnosis, the poor prognosis of the Norwood first stage procedure is unchanged. A systematic search for a restriction of the foramen ovale on foetal echocardiography could optimise neonatal management of this problem.

[Central alveolar hypoventilation syndrome and cerebral venous thrombosis: fortuitous association?]. / Syndrome d'hypoventilation alvéolaire centrale et thrombose veineuse cérébrale: association fortuite?

UNLABELLED: Central hypoventilation syndrome is defined as the failure of automatic control of breathing. Secondary central hypoventilation syndrome should distinguish from congenital central hypoventilation syndrome by brainstem abnormalities, place of respiratory control. CASE REPORTS: We report two clinical cases characterized by late onset central hypoventilation syndrome (three years--six months, and five years old): in the first case the diagnosis was made after general anesthesia and the second one presented with acute nocturnal comatose state. Neuroradiologic investigations showed bilateral cerebral sinus veinous thrombosis without any brainstem lesions. Moreover these children had severe behavior disorders: psychomotor instability, alterations of social relations, language dysfunction, and neurocognitive deficit. This symptomatology seems independent from central hypoventilation syndrome and cerebral venous thrombosis. CONCLUSION: Late onset central hypoventilation syndrome may be associated with cerebral venous thrombosis. Ischemia of central chemoreceptors or integration of their informations could be one of mechanism.

[Infections of cerebrospinal fluid shunts in the child: prevention and treatment]. / Infections des dérivations du liquide céphalorachidien chez l'enfant: prévention et traitement.

Cerebrospinal fluid (CSF) shunting has developed into the mean method of treatment in children with hydrocephalus. Until the last decade, shunt infection was the most important cause of morbidity with a mean rate of 10%. Most of shunt infection (> 90%) are diagnosed within six months after surgery supporting a basic premise of direct contamination at the time of surgery. However, after applying stricter operative and perioperative protocols, some authors reported a dramatically decrease in the incidence of infectious complications. The overall annual risk of shunt infection in a paediatric neurosurgical unit is currently 1%. Risk factors are analysed with emphasis on the choice of preventive treatment. An outline of the protocol for shunt implantation is presented. There is no clearly defined role for prophylactic antibiotic medications in the prevention of shunt infection. The small sample sizes of prospective controlled clinical trials precluded sufficient statistical power. The conclusions of the meta-analyses are not sufficiently robust to resolve the controversy and it is not possible to make recommendations either for or against the use of prophylaxis in shunt surgery. The management of shunt infection is examined with emphasis on antibiotic therapy.

[Severe upper airway obstruction in infectious mononucleosis: a life emergency]. / L'obstruction sévère des voies aériennes supérieures au cours de la mononucléose infectieuse: une urgence vitale.

BACKGROUND: Upper airway obstruction can represent a severe, life-threatening complication of infectious mononucleosis. We report a rare case of airway obstruction in a child with infectious mononucleosis associated with herpes virus infection, and we discuss management strategy that can be proposed in such cases. CASE REPORT: A 9-year-old girl was hospitalised in intensive care unit for obstructive dyspnea during infectious mononucleosis. Despite five days of corticosteroids and tracheal intubation, persistent pharyngo-tonsillar tumefaction led us to perform a surgical adenotonsillectomy. This latter treatment allowed immediate tracheal extubation and a rapid recovery. Histology showed a herpes virus infection associated with infectious mononucleosis. CONCLUSION: Maintaining airway opening in infectious mononucleosis needs sometimes to use instrumental interventions: nasal trumpet, endotracheal intubation, even tracheostomy. Early tonsilloadenoidectomy may relieve airway obstruction and allow a rapid recovery in the most severe cases. Airway obstruction in infectious mononucleosis may be aggravated by concomitant herpes virus infection that should be searched for in this situation, in order to adapt the treatment.

Evaluating the prognosis of multiple, severely traumatized children in the intensive care unit.

OBJECTIVE: To assess the Pediatric Risk of Mortality (PRISM) score and to identify other prognosis factors in severe, multiple trauma in children. DESIGN: Retrospective study over a 9-year period. SETTING: A Pediatric Intensive Care Unit (PICU) in a University Hospital. PATIENTS AND PARTICIPANTS: One hundred and thirty-three traumatized children, 8.6 years (8 months-16 years), were reviewed. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Pediatric Trauma Score (PTS), Injury Severity Score (ISS), New ISS (NISS), Glasgow Coma Scale (GCS) score, and PRISM were calculated. The areas under the Receiver Operating Characteristic (ROC Az) curves, were compared. Univariate and multivariate analyses were performed. The mortality rate was 25.6%. PRISM performed well for discrimination between survivors and non-survivors. Az PRISM 0.9387 (0.029) was not different from Az GCS score 0.9451 (0.027) (P=0.568), but was significantly different from Az ISS 0.756 (0.052) (P<0.001), Az NISS 0.7606 (0.051) (P<0.001), and Az PTS 0.8244 (0.047) (P=0.016). Death was significantly associated with head trauma (P=0.014), PRISM >35, PTS <5, GCS <7, and ISS or NISS >32 (P<0.00001). PRISM >35 (P=0.001) and GCS <7 (P=0.003) were independent risk factors of death. CONCLUSIONS: PRISM is a reliable tool for evaluating the prognosis of multiple, severely traumatized children. Its relative simplicity and the fact that it is extremely widespread as a general prognosis score in PICUs represent other arguments for its use. Due to the leading influence of head trauma on mortality, GCS, a score even simpler than PRISM, showed identical accuracy regarding survival prediction.

EMLA versus nitrous oxide for venous cannulation in children.

We compared EMLA cream with nitrous oxide (N(2)O) for providing pain relief during venous cannulation in children. In a prospective, double-blinded, randomized study, 40 children, 6-11 yr, ASA status I or II, undergoing scheduled surgery received either EMLA cream and inhaled air and oxygen (Group EMLA) or a placebo cream and inhaled 70% N(2)O in oxygen (Group N(2)O) before venous cannulation. Pain was evaluated with a visual analog scale and the Objective Pain Scale. The ease of venous cannulation and the observer's assessment of its efficacy for preventing pain were assessed. Heart rate, blood pressure, respiratory rate, and oxygen saturation were compared before and after venous cannulation. Visual analog scale scores (4.4 +/- 7.5 vs 3.9 +/- 9.3 mm, P = 0.85), Objective Pain Scale scores (median 0 [0-6] vs 0 [0-1], P = 0.61), efficacy (median 0 [0-1] vs 0 [0-1], P = 0.59), and ease of venous cannulation (0 [0-2] vs 0 [0-1], P = 0.84) were not different between EMLA and N(2)O groups, respectively. There was no statistical difference between the groups for the physiologic variables. Minor side effects were significantly more common in the N(2)O group (11 of 20) than in the EMLA group (7 of 20) (P = 0.0248). We conclude that both techniques provided adequate pain relief during venous cannulation, as demonstrated by the low pain scores.

[Short and medium-term results of the Norwood intervention (first stage)]. / Résultats à court et moyen termes de l'intervention de Norwood (première étape).

We report the short and mid-term results of the Norwood procedure (Stage one) in 20 patients with hypoplastic left heart syndrome or univentricular heart with aortic obstruction. Seven patients were prenatally diagnosed. Preoperatively there was obstruction to pulmonary venous return in 6 cases, a mild to moderate tricuspid regurgitation in 6 cases, and 11 patients were supported by mechanical ventilation with multiorgan failure in 5 cases. The surgery was performed under cardiopulmonary bypass at a mean age and weight of 12.9 days and 3 kg, respectively. Nine patients (45%) died within 30 days postoperatively, whereas 5 had delayed sternal closure. The mean duration of mechanical ventilation and ICU stay were 5.7 and 11 days, respectively. Two patients were reoperated for bronchial compression and tracheotomy. Systemic venous thrombosis occurred in 5 patients. In multivariate analysis, an older age at surgery was correlated with postoperative hospital death (p = 0.03). Among the 11 patients discharged home after Stage one procedure, 5 patients underwent balloon dilation for recoarctation and one patient died at home. A bidirectional cavopulmonary anastomosis was performed in 8 patients at a mean age of 0.76 year, with one postoperative death. After a mean follow-up of 1 year (+/- 1.97 years), the 9 remaining patients are all in NYHA class I, at a mean age of 2.2 years. Their mean transcutaneous saturation is 81%. The Norwood procedure (Stage one) is associated with high hospital mortality. However, the functional status of the survivors is correct, like in patients with other type of univentricular hearts. Moreover, although the causes of death in our patients are often not clarified, other studies show that the leading causes of deaths in our patients are often not clarified, other studies show that the leading causes of death in those patients are correctable. In conclusion, the option of a Norwood procedure (Stage one) should be proposed in patients with hypoplastic left heart syndrome (or variant).

Continuous fascia iliaca compartment block in children: a prospective evaluation of plasma bupivacaine concentrations, pain scores, and side effects.

UNLABELLED: We sought to determine the plasma concentrations of bupivacaine and its main metabolite after continuous fascia iliaca compartment (FIC) block in children. Twenty children (9.9 +/- 4 yr, 38 +/- 19 kg) received a continuous FIC block for either postoperative analgesia (n = 16) or femoral shaft fracture (n = 4). A bolus dose of 0.25% bupivacaine (1.56 +/- 0.3 mg/kg) with epinephrine was followed by a continuous administration of 0.1% bupivacaine (0.135 +/- 0.03 mg. kg(-)(1). h(-)(1)) for 48 h. Plasma bupivacaine levels were determined at 24 h and 48 h by using gas liquid chromatography. Heart rate, arterial blood pressure, respiratory rate, side effects, and pain scores were recorded at 4-h intervals during 48 h. No significant differences were found between mean plasma bupivacaine levels at 24 h (0.71 +/- 0.4 microg/mL) and at 48 h (0.84 +/- 0.4 microg/mL) (P = 0.33). FIC block provided adequate analgesia in most cases. No severe adverse effects were noted. We conclude that the bupivacaine plasma concentrations during continuous FIC block in children are within the safety margins. FIC block is well tolerated, and provides satisfactory pain relief in most cases. IMPLICATIONS: In this study, we have shown that, in children, continuous fascia iliaca compartment block, a technique providing neural blockade of the thigh and the anterior part of the knee, was associated with safe plasma bupivacaine concentrations, was well tolerated, and provided satisfactory pain scores in most cases.

Pharmacokinetics of transdermal fentanyl in the peri-operative period in young children.

The pharmacokinetics of transdermal fentanyl were assessed in eight children aged 18-60 months, weighing 11-20 kg and monitored postoperatively in the intensive care unit. A patch, delivering 25 microg.h-1 of fentanyl, was applied for 72 h from the induction of anaesthesia. Plasma fentanyl concentrations were measured over 144 h. Mean (SD) peak concentration of fentanyl was 1.7 (0.66) ng.ml-1 and time to reach maximal plasma concentration was 18 (11) h. The elimination half-life was 14.5 (6.2) h, and the area under the curve for plasma fentanyl concentration (0-144 h) was 86.8 (27) ng.h.ml-1. Maximal fentanyl concentration was negatively correlated with patient age (r = - 0.71; p = 0.049) but not with body weight. These results suggest that the pharmacokinetics of transdermal fentanyl in children are similar to those in adults.

[Severe hyponatremic encephalopathy after pediatric surgery: report of seven cases and recommendations for management and prevention]. / Encéphalopathie hyponatrémique sévère après chirurgie pédiatrique: analyse de sept cas cliniques et recommandations pour un traitement et une prévention efficaces.

BACKGROUND: The infusion of hypotonic solutions in the perioperative period can lead to the development of hyponatraemic encephalopathy which is a severe, life threatening but preventable complication. CLINICAL PRESENTATION: Seven children aged 3-6 yr, ASA 1 or 2, operated on for a scheduled surgical procedure, presented at the 11th postoperative hour with seizures or status epilepticus, associated with vomiting (5/7), and a constant loss of consciousness (median Glasgow Coma Scale at 7), while one child presented with a respiratory arrest. At arrival in ICU, serum sodium was 120 mmol.L-1. All children had received in the perioperative period an hypotonic solution infusion (mainly dextrose 5%), at a high rate for most of them. Management included mechanical ventilation (3/7), antiepileptic drugs (7/7), fluid restriction (7/7), sodium chloride infusion (5/7), and diuretics (6/7). Serum sodium increased to a mean of 135 mmol.L-1 in 12 hours. Six children had a good neurologic outcome while one child died from brain death. CONCLUSION: The use of hypotonic solute in the perioperative period can lead to hyponatremic encephalopathy, a severe neurologic complication of acute hyponatremia. It must be prevented by the use of appropriate solutions i-e isotonic fluids in regards of the low free water elimination capacities of the surgical patient.

[Epstein-Barr virus. An unusual cause of acute myocarditis in children]. / Le virus d'Epstein-Barr. Une cause inhabituelle de myocardite aiguë sévère chez l'enfant.

UNLABELLED: Epstein-Barr virus does not belong to the principal causative agents of acute myocarditis, whose diagnosis and pathogenesis are often difficult to determine. Treatment is also controversial regarding the use of anti-inflammatory or immunosuppressive therapy. CASE REPORT: We describe a 13-month-old girl, admitted for acute heart failure, in whom cardiac catheterization with endomyocardial biopsy revealed an acute myocarditis. Acute viral titers indicated infectious mononucleosis caused by Epstein-Barr virus, and the virus genome was identified with a polymerase chain reaction in the patient's serum. The patient had clinical improvement after corticosteroid administration. CONCLUSION: The different diagnostic tools and the screening examinations to determine the causative agent of myocarditis are discussed. The frequency of Epstein-Barr virus in pathogenesis is also considered. The favorable outcome with immunosuppressive therapy suggests its administration in cases of acute myocarditis.

[Causes of preoperative mortality in transposition of great vessels. 2 cases]. / Causes de mortalité préopératoire de la transposition des gros vaisseaux. A propos de 2 cas.

The prognosis of transposition of the great arteries improved tremendously with the development of an early medico-surgical strategy including balloon atrioseptostomy, prostaglandin infusion and the arterial switch operation within the first days of life. Nevertheless, some patients still die preoperatively. We report on two newborn infants whose fatal outcome was promoted by an inadequate intercirculatory mixing. Since the diagnosis was not immediately made, the restrictive foramen ovale resulted very quickly in deep metabolic acidosis and balloon atrioseptostomy performed yet in the first hours of life could not prevent death. We emphasize the importance of prenatal echographic detection of this defect, only way to plan a balloon septostomy immediately after delivery in those infants suffering from inadequate atrial mixing.

Kidney function in cyclosporine-treated paediatric pulmonary transplant recipients.

BACKGROUND: Lung or heart-lung transplantation is a useful therapy in life-threatening pulmonary disorders during childhood. Cyclosporine A is a major immunosuppressive treatment but has a number of adverse effects including nephrotoxicity. There have been no reports on the long-term evolution of renal function in a large series of paediatric pulmonary transplantation recipients. METHODS: We examined 19 patients followed up for at least 3 years after pulmonary transplantation. The mean time of follow-up was 5.36 years. Kidney function was evaluated by calculation of glomerular filtration rate (GFR) according the Schwartz formula. RESULTS: The GFR was normal before transplantation in all patients. The short-term evolution of GFR was marked by a significant drop during the first and until the 6th month. Then, regardless of the level reached at the end of the 6th month, the GFR remained stable in all patients except one until the end of follow-up. At the end of follow-up, 31% had normal GFR, 57% had mild chronic renal failure, and 5% had advanced renal failure. Hypertension was frequent and associated with renal failure. CONCLUSIONS: Paediatric pulmonary recipients showed evidence of long-term cyclosporine A-associated nephrotoxicity. Most of this toxicity occurred during the first 6 months.

Acute myopathy of intensive care in a child after heart transplantation.

PURPOSE: Acute myopathy of intensive care has been described infrequently in children and never after organ transplantation. We report a case of acute myopathy of intensive care in a child after heart transplantation. CLINICAL FEATURES: An 11-yr-old girl, with no previous medical history, developed acute cardiomyopathy leading to cardiac shock. Family history revealed four cases of unidentified myopathy and/or cardiomyopathy. Preoperatively, while muscle biopsy was near normal, myocardial biopsy revealed non specific mitochondrial disorders. A few days after heart transplantation, she developed acute hypotonia and flaccid quadriplegia, consistent with the diagnosis of acute myopathy of intensive care. Nerve conduction studies were normal, electromyography showed myopathic changes and a new muscle biopsy from quadriceps femoris showed severe loss of myosin filaments and ATPase activity in type 2 fibres. A large laboratory screening failed to demonstrate a metabolic disease or a known myopathy. Muscle strength recovered progressively in three weeks allowing home discharge. A few months later, she was free of symptoms and muscle biopsy showed full histopathological recovery. CONCLUSION: Acute myopathy of intensive care can occur in children after heart transplantation. It should be suspected in the presence of muscle weakness and difficulty in weaning from ventilatory support. Electromyography confirmed a myogenic process and muscle biopsy allowed diagnosis. Full clinical and histopathological recovery usually occur within three weeks.