FrancophonIA/ELRC3.0 huggingface dataset:
English: Hazard Ratio vs AC→D (95% CI)
Danish: Hazard ratio versus AC→D (95 % konfidensinterval)
English: Trazimera 150 mg powder for concentrate for solution for infusion
Danish: Trazimera 150 mg pulver til koncentrat til infusionsvæske, opløsning
English: Bronchospasm
Danish: Hæmatotoksicitet
English: Haemorrhoids
Danish: Rygsmerter
English: DO NOT SHAKE!
Danish: HÆTTEGLASSET MÅ IKKE OMRYSTES!
English: Disease-free survival No. patients with event p<0.0001
Danish: Sygdomsfri overlevelse p < 0,0001
English: • infection of lungs
Danish: •depression betændelse af leveren
English: Justification for not including Braille accepted.
Danish: Fritaget for krav om blindskrift.
English: Gastrointestinal disorders Diarrhoea
Danish: Score Kirurgisk prøvefarvningsmønstre
English: 12 (3 x 4) prefilled pens (multipack)
Danish: 12 (3 x 4) fyldte penne (multipakning)
English: 4 pre-filled pens + 1 needle
Danish: 4 fyldte penne + 1 kanyle
English: MA (EU) number (Invented) name Strength Pharmaceutical Form
Danish: Styrke Lægemiddelform Administration Emballage Indhold (Koncentration)
English: 12 (3 x 4) prefilled pens + 3 needles (multipack)
Danish: 12 (3 x 4) fyldte penne + 3 kanyler (multipakning)
English: 4 single-dose kits (1 vial + 1 prefilled syringe + 1 vial connector + 2 needles)
Danish: 4 enkeltdosissæt (1 hætteglas + 1 fyldt sprøjte + 1 forbindingsled til hætteglas + 2 kanyler)
English: 12 (3 x 4) singledose kits (1 vial + 1 pre-filled syringe + 1 vial connector + 2 needles) (multipack)
Danish: 12 (3 x 4) enkeltdosissæt (1 hætteglas + 1 fyldt sprøjte + 1 forbindingsled til hætteglas + 2 kanyler) (multipakning)
English: The application was withdrawn after ‘day 90'.
Danish: Ansøgningen blev trukket tilbage efter ”dag 90”.
English: The withdrawal letter can be found here.
Danish: Brevet vedrørende tilbagetrækningen kan ses her.
English: It is used either alone or together with other painkillers.
Danish: Det anvendes alene eller sammen med andre smertestillende midler.
English: No new studies were submitted to support this application.
Danish: Der blev ingen nye undersøgelser indsendt til støtte for ansøgningen.
English: It contains the active substance capsaicin (8%).
Danish: Det indeholder det aktive stof capsaicin (8 %).
English: The full European Public Assessment Report for Qutenza can found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports.
Danish: Den fuldstændige EPAR for Qutenza findes på agenturets websted under: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports.
English: The company presented further detailed analysis of the results of some of the studies that had been submitted at time the medicine was first approved.
Danish: Virksomheden fremlagde en mere detaljeret analyse af nogle af undersøgelserne, som var blevet indsendt, da lægemidlet først blev godkendt.
English: What is Qutenza?
Danish: Hvad er Qutenza?
English: The analysis included data on 2,073 diabetic and non-diabetic patients from six studies.
Danish: Analysen omfattede oplysninger om 2 073 patienter med eller uden diabetes fra seks undersøgelser.
English: This means that it stimulates the TRPV1 receptor, which is found in the nociceptors (pain receptors) in the skin.
Danish: Dette betyder, at den stimulerer TRPV1- receptoren, som findes i nocireceptorer (smertereceptorer) i huden.
English: In patients with diabetes, Qutenza is expected to work in the same way as it does in its existing indication.
Danish: Til patienter med diabetes forventedes Qutenza at virke på samme måde, som det virker ved den nuværende indikation.
English: Qutenza contains high doses of capsaicin that are released quickly and overstimulate the TRPV1 receptors.
Danish: Qutenza indeholder store doser af capsaicin, som frigives hurtigt og overstimulerer TRPV1-receptorerne.
English: Overstimulating the receptors makes them become ‘desensitised' and no longer able to respond to the stimuli that normally cause pain in patients with peripheral neuropathic pain.
Danish: Overstimulering af receptorerne gør dem ‘desensibiliserede', så de ikke længere er i stand til at reagere på de stimuli, som normalt forårsager smerte hos patienter med perifere neuropatiske smerter.
English: The active substance in Qutenza, capsaicin, is a substance normally found in chilli peppers that is a ‘selective agonist' of the ‘transient receptor potential vanilloid 1' (TRPV1) receptor.
Danish: Det aktive stof i Qutenza, capsaicin, er et stof, der normalt findes i chillipeber, og som er en selektiv agonist for TRPV1-receptoren (transient receptor potential vanilloid 1).
English: Qutenza is a cutaneous patch (a patch that delivers a medicine to the skin).
Danish: Qutenza er et kutanplaster (et plaster, som afgiver et lægemiddel gennem huden).
English: There are no consequences on the use of Qutenza in its authorised indication.
Danish: Tilbagetrækningen får ingen følger for anvendelse af Qutenza til den godkendte indikation.
English: What was Qutenza expected to be used for?
Danish: Hvad forventedes Qutenza anvendt til?
English: In its official letter, the company stated that its decision to withdraw the application was based on the CHMP's view that the data provided do not allow the Committee to conclude on a positive benefit-risk balance.
Danish: I sit officielle brev oplyste virksomheden, at dets beslutning om at trække ansøgningen tilbage beroede på det synspunkt, som CHMP har fremført om, at udvalget på grundlag af de fremlagte oplysninger ikke kunne nå frem til et positivt risk/benefit-forhold.
English: Patients with diabetes, but especially those with diabetic neuropathic pain, could be put at risk as Qutenza may increase their chances of developing ulcers in the foot, which could lead to serious complications.
Danish: Patienter med diabetes, navnlig patienter med diabetiske neuropatiske smerter, kunne risikere, at Qutenza øgede deres risiko for at få fodsår, hvilket kunne medføre alvorlige komplikationer.
English: How is Qutenza expected to work?
Danish: Hvordan forventes Qutenza at virke?
English: Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Qutenza in diabetic patients did not outweigh its risks.
Danish: På tidspunktet for tilbagetrækningen var CHMP af den opfattelse, at fordelene ved Qutenza hos diabetes-patienter ikke opvejede risiciene.
English: Qutenza has been authorised in the EU since May 2009 and is already used to treat peripheral neuropathic pain (pain that is caused by damage to the nerves in the extremities) in adults who do not have diabetes.
Danish: Qutenza har været godkendt i siden maj 2009 og anvendes allerede til at behandle perifere neuropatiske smerter (smerter som følge af beskadigelse af nerverne i ekstremiteterne) hos voksne, der ikke har diabetes.
English: What is happening with Qutenza for the treatment of neuropathic pain in patients who do not have diabetes?
Danish: Hvad sker der med Qutenza anvendt til behandling af neuropatiske smerter hos patienter, der ikke har diabetes?
English: Based on the review of the data and the company's response to the CHMP lists of questions, at the time of the withdrawal, the CHMP had some concerns and was of the provisional opinion that Qutenza could not have been approved to treat diabetic patients with non-diabetic peripheral neuropathic pain.
Danish: Efter gennemgang af de foreliggende oplysninger og firmaets besvarelse af spørgsmålene fra CHMP var der i CHMP betænkelighed på tilbagetrækningstidspunktet, og udvalgets foreløbige standpunkt var, at Qutenza ikke kunne godkendes til behandling af diabetes patienter med perifere neuropatiske smerter, som ikke er en følge af deres diabetes.
English: The company's analysis was intended to show that diabetic patients with peripheral neuropathic pain not caused by diabetes have as good outcomes with Qutenza as non-diabetic patients.
Danish: Virksomhedens analyse skulle påvise, at diabetes-patienter med perifere neuropatiske smerter, som ikke var forårsaget af diabetes, opnåede ligeså gode resultater med Qutenza som patienter, der ikke havde diabetes.
English: Qutenza was also expected to be used in patients with diabetes who have peripheral neuropathic pain not caused by their diabetes.
Danish: Qutenza forventedes også anvendt til behandling af diabetes-patienter med perifere neuropatiske smerter, som ikke er forårsaget af deres diabetes.
English: The Committee was concerned that it would not be possible in clinical practice to distinguish patients with non-diabetic neuropathic pain from those with diabetic neuropathic pain.
Danish: Udvalget var bekymret for, at det ikke var muligt i klinisk praksis at skelne patienter med perifere neuropatiske smerter, som ikke var en følge af deres diabetes, fra dem med neuropatiske smerter, som var diabetesrelateret.
English: At the time of the initial approval, the evidence supporting the medicine's use in patients with diabetic neuropathic pain was considered insufficient and the CHMP excluded its use in all patients with diabetes.
Danish: Da lægemidlet oprindeligt blev godkendt fandt CHMP, at dokumentationen til underbygning af dets anvendelse hos patienter med diabetiske neuropatiske smerter var utilstrækkelig, og at lægemidlet derfor ikke kunne anvendes til patienter med diabetes.
English: On 14 March 2012, Astellas Pharma Europe B.V. officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a change to the marketing authorisation for Qutenza, which would have extended its use to patients with diabetes who have peripheral neuropathic pain not caused by their diabetes.
Danish: officielt Udvalget for Lægemidler til Mennesker (CHMP), at virksomheden ønsker at trække sin ansøgning om ændring af markedsføringstilladelsen for Qutenza tilbage.
English: *Your doctor may need to increase the frequency of your blood tests to check how well your blood can clot.
Danish: *Det kan være nødvendigt for din læge at øge hyppigheden af dine blodprøver for at kontrollere, hvor godt dit blod kan størkne.
English: • Risk Management Plan (RMP)
Danish: • RisikostyringsPlan (RMP)
English: paritaprevir ANTIBIOTICS (SYSTEMIC ADMINISTRATION)
Danish: paritaprevir ANTIBIOTIKA (SYSTEMISK ADMINISTRATION)
English: MARKETING AUTHORISATION NUMBER(S) EU/1/14/982/001
Danish: MARKEDSFØRINGSTILLADELSESNUMMER (-NUMRE) EU/1/14/982/001
English: See section 5.1 for additional information.
Danish: 5.1 for yderligere oplysninger.
English: Component of a multipack, can't be sold separately.
Danish: Delpakning af multipakning - må ikke sælges separat.
English: The frequency of these events is unknown.
Danish: Hyppigheden af disse bivirkninger er ukendt.
English: • If you have severe liver problems other than hepatitis C.
Danish: • hvis du har andre alvorlige leverproblemer end hepatitis C.
English: You will take Viekirax for either 12 or 24 weeks.
Danish: Du skal tage Viekirax i enten 12 eller 24 uger.
English: to thin the blood
Danish: til fortynding af blodet
English: Main demographics in TURQUOISE-III Characteristics
Danish: Vigtigste demografiske karakteristika i TURQUOISE-III
English: • Anaemia (low number of red blood cells).
Danish: • anæmi (nedsat antal røde blodlegemer).
English: How much to take The recommended dose is two tablets taken together in the morning.
Danish: Så meget skal du tage Den anbefalede dosis er 2 tabletter, der tages samlet om morgenen.
English: DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 15 January 2015
Danish: Dato for første markedsføringstilladelse: 15 januar 2015
English: Q2 2021
Danish: 2. kvartal 2021
English: Follow the dosing recommendations in Table 1.
Danish: Følg doseringsanbefalingerne i tabel 1.
English: Effect of baseline HCV substitutions/polymorphisms on treatment outcome
Danish: Virkning af baseline-HCV-substitutioner/polymorfismer på behandlingsresultatet
English: Table 15 shows SVR rates for these subjects.
Danish: Tabel 15 viser SVR-raterne for disse patienter.
English: Yes (for all three parameters listed above) No (for any parameter listed above) *AFP= serum alpha fetoprotein
Danish: Ja (til alle tre parametre ovenfor) Nej (til et eller flere af parametrene ovenfor) *AFP = serum-alfaføtoprotein
English: Pharmacotherapeutic group: Antivirals for systemic use; direct-acting antivirals, ATC code: J05AX67
Danish: Farmakoterapeutisk klassifikation: Antivirale midler til systemisk brug; direkte virkende antivirale midler; ATC-kode: J05AX67
English: Hepatitis B Virus Reactivation
Danish: Reaktivering af hepatitis B-virus
English: Frequencies are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000).
Danish: Hyppigheden defineres som følger: meget almindelig (≥ 1/10), almindelig (≥ 1/100 til < 1/10), ikke almindelig (≥ 1/1.000 til < 1/100),
English: Arm B 24 Weeks N = 32
Danish: Gruppe B 24 uger N = 32
English: • Feeling weak or lack of energy (asthenia).
Danish: • kraftesløshed, manglende energi (asteni).
English: A 10 kg change in body weight from 76 kg (median weight in the Phase 3 studies) would results in <10% change in ombitasvir exposures, and no change in paritaprevir exposures.
Danish: En ændring på 10 kg i legemsvægt fra 76 kg (median vægt fase 3-studierne) vil medføre en ændring på < 10% i eksponeringen for ombitasvir, og ingen ændring i eksponeringen for paritaprevir.
English: Plasma HCV RNA values were measured during the clinical trials using the COBAS TaqMan HCV test (version 2.0), for use with the High Pure System.
Danish: I de kliniske studier blev HCV-rna-plasmaværdierne målt ved hjælp af COBAS TaqMan HCV-test (version 2.0) til brug med High Pure System.
English: If an HIV protease inhibitor is added (atazanavir, darunavir), rilpivirine exposure may increase even further and is therefore not recommended.
Danish: Hvis en HIVproteasehæmmer tilføjes (atazanavir, darunavir), kan rilpivirin-eksponeringen øges endnu mere; derfor anbefales dette ikke.
English: The assay had a lower limit of quantification (LLOQ) of 25 IU per mL.
Danish: Analysen havde en nedre kvantificeringsgrænse (lower limit of quantification, LLOQ) på 25 IE/ml.
English: AbbVie Ltd Maidenhead SL6 4UB United Kingdom
Danish: AbbVie Ltd Maidenhead SL6 4UB Storbritannien
English: Take two tablets in the morning
Danish: Tag to tabletter om morgenen
English: HIV-1 Co-infection
Danish: Samtidig HIV-1-infektion
English: Treatment of patients with HIV co-infection
Danish: Behandling af patienter med samtidig HIV-infektion
English: Ombitasvir is an inhibitor of HCV NS5A which is essential for viral replication.
Danish: Ombitasvir er en hæmmer af HCV-NS5A, der er afgørende for den virale replikation.
English: The dose of ribavirin was left to the discretion of the investigator, with most patients receiving 600 to 800 mg per day as a starting dose, and most patients also receiving 600 to 800 mg per day at the end of treatment.
Danish: Ribavirin-dosen blev fastsat individuelt efter investigators skøn; de fleste patienter fik 600-800 mg pr. dag som startdosis, og de fleste patienter fik også 600-800 mg pr. dag ved slutningen af behandlingen.
English: 5 of 6 subjects with compensated cirrhosis in each arm achieved SVR12.
Danish: Fem (5) ud af 6 forsøgspersoner med kompenseret cirrose i hver gruppe opnåede SVR12.
English: Take two tablets in the morning.
Danish: Tag to tabletter om morgenen.
English: Clinical studies in subjects with genotype 1 hepatitis C infection
Danish: Kliniske studier med patienter med hepatitis C genotype 1-infektion
English: Coadministration of Viekirax with other antivirals has not been studied and therefore cannot be recommended.
Danish: Samtidig administration af Viekirax og andre antivirale midler er ikke undersøgt og anbefales derfor ikke.
English: • amiodarone
Danish: • amiodaron
English: • Discontinue treatment in patients who develop evidence of hepatic decompensation.
Danish: Behandlingen afbrydes hos patienter, som udvikler tegn på dekompenseret leversygdom.
English: Expected: ↓ esomeprazole, lansoprazole
Danish: Forventet: ↓ esomeprazol, lansoprazol
English: Asthenia Fatigue *Data set includes all genotype 1-infected subjects in Phase 2 and 3 trials including subjects with cirrhosis.
Danish: Træthed *Datasættet omfatter alle genotype 1-smittede patienter i fase 2- og fase 3-studier, herunder patienter med cirrose.
English: While no dose adjustment is necessary for digoxin, appropriate monitoring of serum digoxin levels is recommended.
Danish: Selvom dosisjustering af digoxin ikke er nødvendig, anbefales det at overvåge digoxin-niveauet i serum.
English: SVR12 rates for recommended treatment regimens by patient population HCV Genotype 1b Viekirax and dasabuvir
Danish: SVR12-rater for de anbefalede behandlingsregimer pr. patientpopulation HCV genotype 1b Viekirax og dasabuvir
English: *Note: Follow the genotype 1a dosing recommendations in patients with an unknown genotype 1 subtype or with mixed genotype 1 infection.
Danish: 12 uger *Bemærk: Følg dosisanbefalingerne for genotype 1a hos patienter med en ukendt genotype 1-undertype eller med en blandet genotype 1-infektion.
English: Three interrupted Viekirax and dasabuvir for one to seven days, including one on ethinylestradiol.
Danish: Tre afbrød behandlingen med Viekirax og dasabuvir i 1-7 dage, herunder én, der fik ethinylestradiol.
English: No increase in incidence of ALT elevations was observed with other types of estrogens commonly used for hormone replacement therapy (e.g. estradiol and conjugated estrogens).
Danish: Der sås ingen stigning i incidensen af ALAT-forhøjelser med andre typer af østrogen, som normalt bruges i hormonbehandling (f.eks. estradiol og konjugerede østrogener).
English: INFORMATION IN BRAILLE viekirax
Danish: INFORMATION I BRAILLESKRIFT viekirax
English: 33 out of the 34 subjects (97.1%) achieved SVR12 (96.6% in subjects with genotype 1a infection and 100% in subjects with genotype 1b infection).
Danish: 33 ud af de 34 forsøgspersoner (97,1 %) opnåede SVR12 (96,6 % hos forsøgspersoner med genotype 1a-infektion og 100 % hos forsøgspersoner med genotype 1b-infektion).
English: HIV co-infected patients without suppressive antiretroviral therapy should not be treated with Viekirax.
Danish: Patienter med samtidig HIV-infektion, der ikke er i supprimerende antiretroviral behandling, må ikke få Viekirax.
English: As the incidence of such elevations was 26% among women taking a concomitant ethinylestradiol-containing medicinal product, such medicinal products are contraindicated with Viekirax with or without dasabuvir.
Danish: Da incidensen af sådanne forhøjelser var 26 % blandt de kvinder, der samtidig tog et ethinylestradiol-holdigt lægemiddel, er ethinylestradiol-holdige lægemidler kontraindiceret med Viekirax med eller uden dasabuvir.
English: In contrast, the rate of ALT elevations in subjects using other types of estrogens as typically used in hormonal replacement therapy (i.e., oral and topical estradiol and conjugated estrogens) was similar to the rate observed in subjects who were not using estrogencontaining products (approximately 1% in each group).
Danish: Til gengæld var forekomsten af forhøjet ALAT hos forsøgspersoner, som anvendte andre typer af østrogener, herunder dem, der typisk anvendes til hormonerstatningsbehandling (dvs. estradiol til oral og topikal anvendelse samt konjugerede østrogener), den samme som hos forsøgspersoner, der ikke brugte østrogenholdige lægemidler (ca. 1% i hver gruppe).
English: UNIQUE IDENTIFIER - 2D BARCODE 2D barcode carrying the unique identifier included.
Danish: 17 ENTYDIG IDENTIFIKATOR - 2D-STREGKODE Der er anført en 2D-stregkode, som indeholder en entydig identifikator
English: CONTRACEPTIVES Ethinylestradiol/ norgestimate
Danish: PRÆVENTIONSMIDLER Ethinylestradiol/ norgestimat
English: Rare: may affect up to 1 in 1,000 people
Danish: Sjælden: forekommer hos op til 1 ud af 1.000 behandlede
English: Subjects were on a stable HIV-1 antiretroviral therapy (ART) regimen that included ritonavir-boosted atazanavir or raltegravir, coadministered with a backbone of tenofovir plus emtricitabine or lamivudine.
Danish: Forsøgspersonerne var på en stabil HIV-1-antiretroviral behandling (antiretroviral therapy ( ART)), der omfattede ritonavir-boostet atazanavir eller raltegravir, der blev administreret samtidig med en baggrundsbehandling bestående af tenofovir + emtricitabin eller lamivudin.
English: Contraceptive medicines that contain ethinyl estradiol cannot be used in combination with Viekirax.
Danish: Prævention, der indeholder ethinylestradiol, kan ikke anvendes i kombination med Viekirax.
English: Risk of Hepatic Decompensation and Hepatic Failure in Patients with Cirrhosis
Danish: Risiko for dekompenseret leversygdom og leversvigt hos patienter med cirrose
English: When starting coadministration with Viekirax, administer 0.5 mg tacrolimus once every week.
Danish: Ved administration samtidig med Viekirax skal man i starten administrere 0,5 mg tacrolimus én gang om ugen.
English: Two patients discontinued Viekirax and dasabuvir due to elevated ALT, including one on ethinylestradiol.
Danish: To patienter seponerede Viekirax og dasabuvir på grund af forhøjet ALAT, herunder én, der fik ethinylestradiol.
English: This is due to liver function changes during treatment with Viekirax ± dasabuvir.
Danish: Det skyldes at leverfunktionen ændres under behandling med Viekirax ± dasabuvir.
English: Co-administration of Viekirax with rilpivirine once daily should only be considered in patients without known QTprolongation, and without other QT-prolongation comedications.
Danish: Samtidig administration af Viekirax og rilpivirin én gang dagligt må kun overvejes hos patienter uden kendt QTforlængelse, og som ikke får samtidig behandling med andre QT-forlængende lægemidler.
English: The combination carries an increased risk for hyperbilirubinemia (including ocular icterus), in particular when ribavirin is part of the hepatitis C regimen.
Danish: Kombinationen giver øget risiko for hyperbilirubinæmi (herunder okulær ikterus), især nårribavirin indgår i hepatitis C-regimet.
English: ANTIPSYCHOTICS Lurasidone
Danish: ANTIPSYKOTIKA Lurasidon
English: The safety summary is based on pooled data from phase 2 and 3 clinical trials in more than 2,600 subjects who received Viekirax and dasabuvir with or without ribavirin.
Danish: Sikkerhedsprofilen er baseret på samlede data fra kliniske fase 2- og fase 3-studier med over 2.600 patienter, der fik Viekirax og dasabuvir med eller uden ribavirin.
English: ↓diazepam 1.18
Danish: Diazepam Viekirax ↓diazepam 1,18
English: SVR12, n/N (%) [95% CI] Outcome for subjects without SVR12 On-treatment virologic failure Post-treatment relapse
Danish: SVR12, n/N (%) [95 %-KI] Resultat for patienter, uden SVR12 Virologisk svigt under behandling Recidiv efter behandling
English: Viekirax is an antiviral medicine used to treat adults with chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus).
Danish: Viekirax er et antiviralt lægemiddel, der bruges til behandling af voksne med kronisk (vedvarende) hepatitis C (en infektionssygdom i leveren, der skyldes hepatitis C-virus).
English: • Monitor for clinical signs and symptoms of hepatic decompensation (such as ascites, hepatic encephalopathy, variceal haemorrhage).
Danish: For patienter med cirrose: Overvåg for kliniske tegn og symptomer på dekompenseret leversygdom (såsom ascites, hepatisk encefalopati og varice-blødning).
English: While ombitasvir exposures increased in a dose proportional manner, paritaprevir and ritonavir exposures increased in a more than dose proportional manner.
Danish: Ombitasvir-eksponeringen steg proportionalt med dosis, og paritaprevir- og ritonavireksponeringen steg mere end proportionalt med dosis.
English: The majority of adverse reactions presented in Table 3 were of grade 1 severity in Viekirax and dasabuvircontaining regimens.
Danish: De fleste af bivirkningerne i tabel 3 var af sværhedsgrad 1 i regimer med Viekirax og dasabuvir-holdige regimer.