FrancophonIA/ELRC3.0 huggingface dataset:
English: If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.
Danish: De må kun bruge disse lægemidler, hvis andre lægemidler ikke kan anvendes, og kun efter en lægelig vurdering og under tæt lægelig overvågning for kortikosteroid-bivirkninger.
English: anaemia1
Danish: anæmi1
English: Cobicistat was not mutagenic or clastogenic in conventional genotoxicity assays.
Danish: Cobicistat var ikke mutagent eller klastogent i konventionelle genotoksicitets-assays.
English: As such, tenofovir alafenamide exposures following administration of Genvoya are not expected to be further increased when used in combination with another P-gp and/or BCRP inhibitor (e.g., ketoconazole).
Danish: Som sådan forventes det ikke, at eksponeringer for tenofoviralafenamid efter administration af Genvoya øges yderligere, når det anvendes i kombination med en anden P-gp- og/eller BRCP-hæmmer (f.eks. ketokonazol).
English: Tenofovir alafenamide is transported by P-gp and BCRP.
Danish: Tenofoviralafenamid transporteret af P-gp og BCRP.
English: In studies in treatment-naïve patients, increases from baseline were observed in both treatment groups for the fasting lipid parameters total cholesterol, direct low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, and triglycerides at Week 144.
Danish: I studier med behandlingsnaive patienter blev der observeret stigninger fra baseline i begge behandlingsgrupper for de fastende lipidparametre total kolesterol, direkte lavdensitets-lipoprotein (LDL)- og højdensitets-lipoprotein (HDL)-kolesterol og triglycerider ved uge 144.
English: Although there were no new safety issues identified, the implications of increased emtricitabine exposure remain uncertain (see sections 4.8 and 5.2).
Danish: Skønt der ikke identificeredes nye sikkerhedsproblemer, er implikationerne af øget eksponering for emtricitabin stadig usikre (se pkt.
English: Patients receiving Genvoya or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases.
Danish: Patienter, som får Genvoya eller anden antiretroviral behandling, har fortsat risiko for opportunistiske infektioner eller andre hiv-relaterede komplikationer og bør derfor følges nøje af læger med erfaring i behandlingen af patienter med hiv-associerede sygdomme.
English: • In adults and adolescents aged from 12 years and with body weight at least 35 kg
Danish: • Hos voksne og unge i alderen 12 år og ældre, med en legemsvægt på mindst 35 kg
English: FTC/tenofovir disoproxil plus boosted atazanavir E/C/F/TDF
Danish: EFV/FTC/tenofovirdisoproxil FTC/tenofovirdisoproxil plus boosted atazanavir E/C/F/TDF
English: Once you start taking Genvoya, look out for:
Danish: Når De begynder med at tage Genvoya, skal De holde øje med:
English: However, tenofovir disoproxil reduced the viability index and weight of pups in a peri-postnatal toxicity study at maternally toxic doses.
Danish: Tenofovirdisoproxil reducerede imidlertid afkommets levedygtighed og vægt i peri-postnatale toksicitetsstudier ved doser, der var toksiske for moderen.
English: digoxin, disopyramide, flecainide, lidocaine, mexiletine, propafenone, metoprolol, timolol, amlodipine, diltiazem, felodipine, nicardipine, nifedipine and verapamil
Danish: - digoxin, disopyramid, flecainid, lidocain, mexiletin, propafenon, metoprolol, timolol, amlodipin, diltiazem, felodipin, nicardipin, nifedipin og verapamil
English: Eighty-six percent of patients (62/72) were HBV suppressed (HBV DNA < 29 IU/mL) and 42% (30/72) were HBeAg positive at baseline.
Danish: 86 procent af patienterne (62/72) var HBV-supprimerede (HBV DNA < 29 IE/ml), og 42 % (30/72) var HBeAg-positive ved baseline.
English: When administering with Genvoya, the maximum daily dose of itraconazole should not exceed 200 mg per day.
Danish: Ved samtidig administration af Genvoya bør den maksimale daglige dosis af itraconazol ikke overskride 200 mg daglig.
English: Co-administration of Genvoya and sildenafil for the treatment of pulmonary arterial hypertension is contraindicated.
Danish: Samtidig administration af Genvoya og sildenafil til behandling af pulmonal arteriel hypertension er kontraindiceret.
English: Inhibition of integrase prevents the integration of HIV-1 deoxyribonucleic acid (DNA) into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the viral infection.
Danish: Hæmning af integrase forhindrer integration af hiv 1 deoxyribonukleinsyre (-dna) i det humane dna og blokerer dannelsen af hiv 1-provirus og propagation af den virale infektion.
English: Genvoya film-coated tablets are green, capsule-shaped tablets, debossed on one side with “GSI” and the number “510” on the other side of the tablet.
Danish: Genvoya filmovertrukne tabletter er grønne, kapselformede tabletter, på den ene side præget med ”GSI” og tallet ”510”, på den anden side af tabletten.
English: If you vomit less than 1 hour after taking Genvoya, take another tablet with food.
Danish: Hvis De kaster op mindre end 1 time efter, De har taget Genvoya, skal De tage en ny tablet sammen med mad.
English: Genvoya can cause dizziness.
Danish: Genvoya kan forårsage svimmelhed.
English: The mean plasma to blood drug concentration ratio was 1.37.
Danish: Forholdet mellem gennemsnitlig lægemiddelkoncentration i plasma og blodet var 1,37.
English: Elvitegravir, emtricitabine, and tenofovir alafenamide demonstrated synergistic antiviral activity in cell culture.
Danish: Elvitegravir, emtricitabin og tenofoviralafenamid viste synergistisk antiviral aktivitet i cellekultur.
English: Based on these limited data, the safety profile of Genvoya in patients with HIV/HBV co-infection was similar to that in patients with HIV-1 monoinfection.
Danish: Baseret på disse begrænsede data lignede sikkerhedsprofilen for Genvoya hos patienter co-inficeret med hiv/HBV den for patienter med hiv 1-monoinfektion.
English: • antidepressants, used to treat depression: medicines containing trazodone or escitalopram
Danish: • antidepressiva, anvendes til at behandle depression: lægemidler, der indeholder trazodon eller escitalopram
English: The mean age was 58 years (range 24-82), with 63 patients (26%) who were ≥ 65 years of age.
Danish: Gennemsnitsalderen var 58 år (interval 24-82) med 63 patienter (26 %), som var ≥ 65 år.
English: Inhibition of CYP3A-mediated metabolism by cobicistat enhances the systemic exposure of CYP3A substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism.
Danish: Hæmning af CYP3A-medieret metabolisme af cobicistat øger den systemiske eksponering over for CYP3A-substrater, såsom elvitegravir, hvor biotilgængeligheden er begrænset og halveringstiden er forkortet af den CYP3A-afhængige metabolisme.
English: Thirteen percent of the emtricitabine dose was recovered in urine as three metabolites.
Danish: 13 % af emtricitabindosen blev genfundet i urinen som tre metabolitter.
English: However, based on the information retrieved in literature and in the product information of integrase inhibitors containing medicinal products, it could be concluded that the following psychiatric disorders: depression, suicidal ideation and suicidal behaviour (particularly in patients with pre-existing history of psychiatric illness) are class-effect of integrase inhibitors and these are listed in the SmPC of other medicinal products containing integrase inhibitors in monotherapy and in fixed-dose combination (FDC).
Danish: På baggrund af information fra litteraturen og i produktinformationen for lægemidler der indeholder integrasehæmmere, kunne det dog konkluderes, at følgende psykiske lidelser: depression, selvmordstanker og selvmordsadfærd (især hos patienter med psykisk sygdom i anamnesen) er klasseeffekt af integrasehæmmere, og disse er anført i produktresuméet for andre lægemidler indeholdende integrasehæmmere i monoterapi og i fastdosiskombination.
English: Because there is a lower tenofovir exposure in rats and mice after the administration of tenofovir alafenamide compared to tenofovir disoproxil, carcinogenicity studies and a rat peri-postnatal study were conducted only with tenofovir disoproxil.
Danish: Da der er en lavere eksponering for tenofovir hos rotter og mus efter administration af tenofoviralafenamid sammenlignet med tenofovirdisoproxil, blev der kun udført karcinogenicitetsstudier og et peri-postnatalt studie hos rotter med tenofovirdisoproxil.
English: EVG = elvitegravir; COBI = cobicistat; FTC = emtricitabine; TAF = tenofovir alafenamide fumarate; TFV = tenofovir N/A = not applicable
Danish: EVG = elvitegravir; COBI = cobicistat; FTC = emtricitabin; TAF = tenofoviralafenamidfumarat; TFV = tenofovir N/A = ikke relevant
English: • adefovir dipivoxil
Danish: • adefovirdipivoxil
English: • ergot derivatives: dihydroergotamine, ergometrine, ergotamine
Danish: • ergot-derivater: dihydroergotamin, ergometrin, ergotamin
English: Genvoya demonstrated statistical superiority in achieving HIV-1 RNA < 50 copies/mL when compared to E/C/F/TDF at Week 144.
Danish: Genvoya udviste statistisk superioritet ved at opnå hiv 1-rna < 50 kopier/ml, sammenlignet med E/C/F/TDF ved uge 144.
English: Following administration of tenofovir alafenamide, plasma [14C]-radioactivity showed a time-dependent profile with tenofovir alafenamide as the most abundant species in the initial few hours and uric acid in the remaining period.
Danish: Efter administration af tenofoviralafenamid viste plasma [14C]-radioaktivitet en tidsafhængig profil med tenofoviralafenamid som det hyppigste stof i de første par timer og urinsyre i den resterende periode.
English: Of the 10 patients who were not HBV suppressed at baseline (HBV DNA ≥ 29 IU/mL), 7 became suppressed, 2 remained detectable, and 1 had missing data.
Danish: Ud af de 10 patienter, som ikke var supprimerede ved baseline (HBV DNA ≥ 29 IE/ml), blev 7 supprimerede, 2 forblev detekterbare, og 1 havde manglende data.
English: Cobicistat has no detectable antiviral activity against HIV-1 and does not antagonise the antiviral effects of elvitegravir, emtricitabine, or tenofovir.
Danish: Cobicistat har ingen målelig antiviral aktivitet mod hiv 1, og antagoniserer ikke de antivirale virkninger af elvitegravir, emtricitabin og tenofovir.
English: Cobicistat is also a weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6.
Danish: Cobicistat er også en svag CYP2D6-hæmmer, og den metaboliseres i mindre grad af CYP2D6.
English: Green, capsule-shaped, film-coated tablet of dimensions 19 mm x 8.5 mm, debossed with “GSI” on one side of the tablet and “510” on the other side of the tablet.
Danish: Grønne, kapselformede, filmovertrukne tabletter, der måler 19 mm x 8,5 mm, præget med ”GSI” på den ene side af tabletten og med ”510” på den anden side af tabletten.
English: Based on drug-drug interaction studies conducted with Genvoya or the components of Genvoya, no clinically significant drug-drug interactions have been either observed or are expected between the components of Genvoya and the following medicinal products: entecavir, famciclovir, ribavirin, famotidine, and omeprazole.
Danish: Baseret på lægemiddelinteraktionsstudier udført med Genvoya eller Genvoya-komponenterne, er der ikke blevet observeret og der forventes heller ikke nogen klinisk signifikante lægemiddelinteraktioner mellem Genvoya-komponenterne og de følgende lægemidler: entecavir, famciclovir, ribavirin, famotidin og omeprazol.
English: Following oral administration with food in HIV-1 infected patients, peak plasma concentrations were observed approximately 4 hours post-dose for elvitegravir, 3 hours post-dose for cobicistat, 3 hours post-dose for emtricitabine, and 1 hour post-dose for tenofovir alafenamide.
Danish: Efter oral administration sammen med mad hos hiv 1-inficerede patienter blev maksimale plasmakoncentrationer observeret ca. 4 timer efter dosering for elvitegravir, 3 timer efter dosering for cobicistat, 3 timer efter dosering for emtricitabin og 1 time efter dosering for tenofoviralafenamid.
English: At screening, 42% of patients were receiving FTC/tenofovir disoproxil plus atazanavir (boosted by either cobicistat or ritonavir), 32% of patients were receiving E/C/F/TDF, and 26% of patients were receiving EFV/FTC/tenofovir disoproxil.
Danish: Ved screening fik 42 % af patienterne FTC/tenofovirdisoproxil plus atazanavir (boosted enten ved cobicistat eller ritonavir), 32 % af patienterne fik E/C/F/TDF, og 26 % af patienterne fik EFV/FTC/tenofovirdisoproxil.
English: Emtricitabine exposures were unaffected by a light or high-fat meal.
Danish: Emtricitabin-eksponeringer blev ikke påvirket af et let måltid eller et måltid med højt fedtindhold.
English: The results reported from a prospective study (IMPAACT P1026s) showed that treatment with cobicistat and elvitegravir-containing regimens during pregnancy results in lower elvitegravir and cobicistat exposures (Table 7).
Danish: De indberettede resultater fra et prospektivt studie (IMPAACT P1026s) viste, at behandling med regimer indeholdende cobicistat og elvitegravir under graditet medfører lavere eksponering for elvitegravir og cobicistat (Tabel 7).
English: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide This medicine is subject to additional monitoring.
Danish: Elvitegravir/cobicistat/emtricitabin/tenofoviralafenamid Dette lægemiddel er underlagt supplerende overvågning.
English: The interactions described are based on studies conducted with Genvoya, or the components of Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide), as individual agents and/or in combination, or are potential drug-drug interactions that may occur with Genvoya.
Danish: De beskrevne interaktioner er baseret på studier udført med Genvoya eller Genvoya-komponenterne (elvitegravir, cobicistat, emtricitabin og tenofoviralafenamid) som individuelle stoffer og/eller i kombination, eller de er mulige lægemiddelinteraktioner, der kan forekomme med Genvoya.
English: No dose adjustment of clarithromycin is required.
Danish: Dosisjustering af clarithromycin er ikke nødvendig.
English: Medicinal products that are highly dependent on CYP3A metabolism and have high first pass metabolism are the most susceptible to large increases in exposure when co-administered with cobicistat (see “Concomitant use contraindicated” and section 4.3).
Danish: Lægemidler, der er meget afhængige af CYP3A-metabolismen og som har en høj first pass-metabolisme, er mest udsatte for meget øget eksponering, når de administreres sammen med cobicistat (se ”Samtidig brug kontraindiceret” og pkt.
English: A study of the pharmacokinetics of cobicistat-boosted elvitegravir was performed in non-HIV-1 infected patients with moderate hepatic impairment (Child-Pugh Class B).
Danish: Et farmakokinetikstudie af cobicistat-boosted elvitegravir blev udført hos non-hiv 1-inficerede patienter med moderat nedsat leverfunktion (Child-Pugh klasse B).
English: Table 4: Virologic outcomes of Study GS-US-292-0109 at Weeks 48a and 96b
Danish: Tabel 4: Virologiske resultater af studie GS-US-292-0109 ved uge 48a og 96b Uge 48
English: Both elvitegravir and cobicistat are primarily metabolised and eliminated by the liver.
Danish: Både elvitegravir og cobicistat metaboliseres og udskilles primært i leveren.
English: Tenofovir alafenamide is a substrate of OATP in vitro.
Danish: Tenofoviralafenamid er et substrat for OATP in vitro.
English: In human clinical studies, a 10 mg oral dose of tenofovir alafenamide in Genvoya resulted in tenofovir diphosphate concentrations > 4-fold higher in PBMCs and > 90% lower concentrations of tenofovir in plasma as compared to a 245 mg oral dose of tenofovir disoproxil (as fumarate) in E/C/F/TDF.
Danish: I kliniske studier af mennesker resulterede en 10 mg oral dosis af tenofoviralafenamid i Genvoya i tenofovirdiphosphatkoncentrationer > 4 gange højere i PBMC'er og > 90 % lavere koncentrationer af tenofovir i plasma sammenlignet med en 245 mg oral dosis af tenofovirdisoproxil (som fumarat) i E/C/F/TDF.
English: • If you are allergic to elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide or any of the other ingredients of this medicine (listed in section 6 of this leaflet).
Danish: • Hvis De er allergisk over for elvitegravir, cobicistat, emtricitabin, tenofoviralafenamid eller et af de øvrige indholdsstoffer i Genvoya (angivet i punkt 6 i denne indlægsseddel).
English: The effect of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of elvitegravir or cobicistat has not been studied.
Danish: Virkningen af svært nedsat leverfunktion (Child-Pugh klasse C) på elvitegravirs og cobicistats farmakokinetik er ikke undersøgt.
English: Elvitegravir was negative in an in vitro bacterial mutagenicity test (Ames test) and negative in an in vivo rat micronucleus assay at doses up to 2,000 mg/kg.
Danish: Elvitegravir var negativ i en in vitro bakteriel mutagenicitetstest (Ames-test) og negativ i en in vivo mikronukleusanalyse med rotter ved doser op til 2.000 mg/kg.
English: The median increase from baseline for those parameters was greater in the Genvoya group compared with the E/C/F/TDF group at Week 144 (p < 0.001 for the difference between treatment groups for fasting total cholesterol, direct LDL- and HDL-cholesterol, and triglycerides).
Danish: Den mediane stigning fra baseline for disse parametre var større i Genvoya-gruppen sammenlignet med E/C/F/TDFgruppen ved uge 144 (p < 0,001 for forskellen mellem behandlingsgrupperne for fastende total kolesterol, direkte LDL- og HDL-kolesterol samt triglycerider).
English: • antacids, used to treat heartburn or acid reflux (see also section 3, How to take Genvoya).
Danish: • syreneutraliserende midler, anvendes til at behandle halsbrand (se også punkt 3, Sådan skal De tage Genvoya).
English: ANTICOAGULANTS Dabigatran
Danish: ANTIKOAGULANTIA Dabigatran
English: If a patient misses a dose of Genvoya by more than 18 hours, the patient should not take the missed dose and simply resume the usual dosing schedule.
Danish: Hvis patienten glemmer at tage en dosis Genvoya i mere end 18 timer, skal patienten ikke tage den manglende dosis, men blot fortsætte med den normale doseringsplan.
English: At the start of treatment with Genvoya, the 72 patients had been HIV suppressed (HIV-1 RNA < 50 copies/mL) for at least 6 months with or without suppression of HBV DNA and had compensated liver function.
Danish: Ved starten af behandlingen med Genvoya havde 72 patienter været hiv-supprimerede (hiv-1 RNA < 50 kopier/ml) i mindst 6 måneder med eller uden supprimering af HBV DNA, og de havde kompenseret leverfunktion.
English: Do not take antacids or multivitamins at the same time as Genvoya.
Danish: Tag ikke syreneutraliserende midler eller multivitaminer på samme tidspunkt som Genvoya.
English: It is recommended that the international normalised ratio (INR) be monitored upon co-administration of Genvoya.
Danish: Det anbefales at overvåge den internationale normaliserede ratio (INR) ved samtidig administration af Genvoya.
English: Cobicistat is 97-98% bound to human plasma proteins and the mean plasma to blood drug concentration ratio was 2.
Danish: Cobicistat er 97-98 % bundet til humane plasmaproteiner og forholdet mellem gennemsnitlig lægemiddelkoncentration i plasma og blodet var 2.
English: When administering with Genvoya, the maximum daily dose of ketoconazole should not exceed 200 mg per day.
Danish: Ved samtidig administration af Genvoya bør den maksimale daglige dosis af ketoconazol ikke overskride 200 mg daglig.
English: Cobicistat reversibly inhibits MATE1, and concentrations of metformin may be increased when co-administered with Genvoya.
Danish: Cobicistat hæmmer MATE1 reversibelt, og koncentrationer af metformin kan øges ved samtidig administration af Genvoya.
English: Elvitegravir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A may affect the exposure of elvitegravir.
Danish: Elvitegravir metaboliseres primært af CYP3A, og lægemidler, der inducerer eller hæmmer CYP3A kan påvirke eksponeringen of elvitegravir.
English: Each tablet contains 61 mg lactose (as monohydrate).
Danish: Hjælpestoffer, som behandleren skal være opmærksom på Hver tablet indeholder 61 mg lactose (som monohydrat).
English: Table 7: Changes in pharmacokinetic parameters from the IMPAACT P1026s study for elvitegravir and cobicistat in women receiving cobicistat and elvitegravir-containing regimens during the second and third trimesters of pregnancy compared to paired postpartum data
Danish: Tabel 7: Ændringer i farmakokinetiske elvitegravir- og cobisistat-parametre fra studiet IMPAACT P1026s hos kvinder, der fik regimer indeholdende cobicistat og elvitegravir i andet og tredje trimester af graviditeten, sammenlignet med parrede postpartumdata
English: Genvoya should not be co-administered with other antiretroviral medicinal products.
Danish: Genvoya bør ikke administreres samtidig med andre antiretrovirale lægemidler.
English: Cobicistat is a selective, mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A subfamily.
Danish: Cobicistat er en selektiv, mekanismebaseret hæmmer af cytokrom P450 (CYP)-enzymer fra CYP3A-undergruppen.
English: suicidal ideation and suicide attempt (in patients with a pre-existing history of depression or psychiatric illness), depression2
Danish: selvmordstanker og selvmordsforsøg (hos patienter med depression eller psykisk sygdom i anamnesen), depression2
English: Do not stop taking Genvoya without talking to your doctor.
Danish: Hold ikke op med at tage Genvoya Hold ikke op med at tage Genvoya uden at tale med Deres læge.
English: There are limited clinical data on the use of Genvoya in HIV/HBV co-infected patients who are treatment-naïve.
Danish: Der er begrænsede kliniske data vedrørende brugen af Genvoya hos patienter med samtidig infektion med hiv/HBV, som er behandlingsnaive.
English: Similar patterns of psychiatric disorders were observed in comparative studies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), which lists these events in its product information (studies GS-US-292-0104 or GS-US-292-0111).
Danish: Der blev observeret lignende mønstre for psykiske lidelser i komparative studier af elvitegravir/cobicistat/emtricitabin/tenofoviralafenamid (E/C/F/TAF) versus elvitegravir/cobicistat/emtricitabin/tenofovirdisoproxilfumarat (E/C/F/TDF), som angiver disse hændelser i produktinformationen (studie GS-US-292-0104 eller GS-US-292-0111).
English: • sedatives and hypnotics, used to treat anxiety: buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem and lorazepam
Danish: • sedativa og hypnotika, anvendes til at behandle angst: - buspiron, clorazepat, diazepam, estazolam, flurazepam, zolpidem og lorazepam
English: betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.
Danish: betamethason, budesonid, fluticason, mometason, prednison og triamcinolon.
English: Adolescents and children 6 years of age and older, who weigh at least 25 kg: one tablet each day with food
Danish: Unge og børn i alderen 6 år og ældre, som vejer mindst 25 kg: en tablet om dagen sammen med mad
English: Sofosbuvir metabolite GS-331007:
Danish: Sofosbuvir metabolit GS-331007:
English: In treatment-naïve patients, a mean change from baseline of 0.04 ± 0.12 mg/dL (3.5 ± 10.6 µmol/L) was observed after 144 weeks of treatment.
Danish: Hos behandlingsnaive patienter blev der observeret en gennemsnitlig ændring fra baseline på 0,04 ± 0,12 mg/dl (3,5 ± 10,6 μmol/l) efter 144 ugers behandling.
English: The safety and efficacy of Genvoya in patients with significant underlying liver disorders have not been established.
Danish: Genvoyas sikkerhed og virkning hos patienter med signifikant underliggende leversygdom er ikke klarlagt.