natgillin/translations-raw huggingface dataset:
Tell your doctor or healthcare professional immediately if you notice such reactions during the infusion of this medicine.
Zdravniku ali zdravstvenem delavcu takoj povejte, če opazite med infundiranjem tega zdravila take znake.
Connect the other end to the injection set (e.g. butterfly / winged infusion needle or infusion catheter).
Drugi konec povežite s pripomočkom za injiciranje (npr. metuljček/infuzijska igla s krilci ali infuzijski kateter).
Hypersensitivity reactions (including tachycardia, hypotension, confusion, syncope, oxygen consumption decreased and pharyngeal oedema)
Bolezni imunskega sistema preobčutljivostne reakcije (vključno s tahikardijo, hipotenzijo, zmedenostjo, sinkopo, zmanjšano porabo kisika in faringealnim edemom)
The infusion solution is normally given over about 15 minutes (about 0.08 ml of solution per kg body weight each min).
Raztopina se običajno infundira 15 minut (približno 0,08ml raztopine na kg telesne mase vsako minuto).
Frequency not known (frequency cannot be estimated from the available data) Pain to the lymph glands (oval-shaped masses of tissue that are distributed throughout the body and which may be palpable for example in the armpit, groinor neck), swollen face, swollen eyes and lips.
Neznana pogostnost (pogostnosti ni mogoče oceniti iz razpoložljivih podatkov) bolečine v bezgavkah (tkivo ovalne oblike, porazdeljeno po vsem telesu, ki je na primer lahko tipno pod pazduho, v dimljah ali vratu), otekel obraz, otekle oči in ustnice.
Emphysema develops when the lack of alpha1-proteinase inhibitor results in a condition in which neutrophil elastase is not being properly controlled, damaging the tiny air sacs in the lungs through which oxygen passes into the body.
Emfizem se razvije, ko pomanjkanje zaviralca alfa1-proteinaze povzroči stanje, pri katerem nevtrofilna elastaza ni pod ustreznim nadzorom, kar poškoduje drobne zračne mešičke v pljučih, skozi katere kisik prehaja v telo.
At screening, serum alpha1-proteinase inhibitor levels were between 3.2 and 10.1 M (mean of 5.6 M).
Pri presejanju so bile ravni zaviralca alfa1-proteinaze v serumu med 3,2 in 10,1 M (povprečje 5,6 M).
The annual rate of lung density decline, as measured by CT scan at total lung capacity (TLC) over 2 years was lower with Respreeza (-1.45 g/L) as compared with placebo (-2.19 g/L), reflecting a 34% reduction (p = 0.017, 1-sided).
Letna stopnja upada pljučne gostote, izmerjene na sliki CT, pri skupni pljučni kapaciteti (TLC, total lung capacity) v 2-letnem obdobju je bila nižja pri zdravilu Respreeza (-1,45 g/l) v primerjavi s placebom (-2,19 g/l), kar kaže na 34odstotno zmanjšanje (p = 0,017; 1-stransko).
The European Medicines Agency has waived the obligation to submit the results of studies with Respreeza in all subsets of the pediatric population in chronic obstructive pulmonary disease (COPD) due to alpha1-proteinase inhibitor deficiency (see section 4.2 for information on pediatric use).
Evropska agencija za zdravila je odstopila od zahteve za predložitev rezultatov študij z zdravilom Respreeza za vse podskupine pediatrične populacije s kronično obstruktivno pljučno boleznijo (KOPB) zaradi pomanjkanja zaviralca alfa1-proteinaze (za podatke o uporabi pri pediatrični populaciji glejte poglavje 4.2).
It is unknown whether Respreeza passes into human milk.
Ni znano, ali zdravilo Respreeza prehaja v materino mleko.
Slowly open the roller clamp on the administration set and let Respreeza flow until it reaches the end of the tubing with no air bubbles.
Počasi odpirajte stišček na pripomočku za apliciranje in pustite zdravilo Respreeza teči, da doseže konec cevk brez zračnih mehurčkov.
No animal reproduction studies have been conducted with Respreeza and its safety for use in human pregnancy has not been established in controlled clinical trials.
Študij razmnoževanja pri živalih z zdravilom Respreeza niso opravili, zato varnost za uporabo med nosečnostjo pri ljudeh ni bila ugotovljena v nadzorovanih kliničnih preskušanjih.
This medicine is a white to off-white powder.
To zdravilo je bel do belkast prašek.
The measures taken are considered effective for viruses such as human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, hepatitis C virus, and parvovirus B19 virus.
Uvedeni ukrepi veljajo za učinkovite proti virusom, kot so virus humane imunske pomanjkljivosti (HIV), virus hepatitisa A, virus hepatitisa B in virus hepatitisa C ter parvovirus B19.
minutes (4 g and 5 g presentation).
4 g in 5 g).
Do not use this medicine after the expiry date which is stated on the outer carton and the vial labels after EXP.
Tega zdravila ne smete uporabljati po datumu izteka roka uporabnosti, ki je naveden na zunanji škatli in nalepki viale poleg oznake EXP. Rok uporabnosti zdravila se izteče na zadnji dan navedenega meseca.
Nine subjects received a single 60 mg / kg bw dose of Respreeza followed by a comparator product, and 9 subjects received comparator product followed by a single 60 mg / kg bw dose of Respreeza, with a wash-out period of 35 days between doses.
Devet oseb je prejelo en 60 mg/kg tm odmerek zdravila Respreeza, ki mu je sledilo primerjalno zdravilo, in 9 oseb je prejelo primerjalno zdravilo, ki mu je sledil en 60 mg/kg tm odmerek zdravila Respreeza, z obdobjem izpiranja 35 dni med odmerki.
It is strongly recommended that every time you receive a dose of Respreeza the name and batch number of the product are recorded in order to maintain a record of the batches used.
Močno se priporoča, da se po vsaki uporabi odmerka zdravila Respreeza zabeleži ime in številka serije zdravila, da se ohranja evidenca uporabljenih serij.
The reconstituted solution should be infused intravenously using a separate dedicated infusion line at an infusion rate of about 0.08 ml / kg bw/ min.
Rekonstituirano raztopino je treba infundirati intravensko s posebno namensko infuzijsko linijo s hitrostjo infundiranja približno 0,08 ml/kg telesne mase/min.
In case of self-administration / home-treatment, stop the infusion immediately and contact your doctor or healthcare professional.
Pri samoinfundiranju/zdravljenju doma infuzijo takoj ustavite in se obrnite na zdravnika ali zdravstvenega delavca.
Frequency of Adverse Reactions (ARs) in clinical studies and post-marketing experience with Respreeza
Pogostnost neželenih učinkov v kliničnih študijah in iz izkušenj v obdobju trženja zdravila Respreeza
The studies investigated the effect of Respreeza on the progression of emphysema, assessed by the decline of lung density, measured by computer tomography (CT).
V študijah so preučevali učinek zdravila Respreeza na napredovanje emfizema, kar je bilo ocenjeno z upadom gostote pljuč, izmerjeno z računalniško tomografijo (CT, computer tomography).
Respreeza is indicated for maintenance treatment, to slow the progression of emphysema in adults with documented severe alpha1-proteinase inhibitor deficiency (e.g. genotypes PiZZ, PiZ(null), Pi(null,null), PiSZ).
Zdravilo Respreeza je indicirano za vzdrževalno zdravljenje za upočasnitev napredovanja emfizema pri odraslih z dokumentiranim hudim pomanjkanjem zaviralca alfa1-proteinaze (npr. genotipi PiZZ, PiZ(nič), Pi(nič,nič), PiSZ).
OUTER BOX
ZUNANJA ŠKATLA
After the first infusions, you or your caregiver might also administer Respreeza, but only after receiving adequate training.
Po prvem infundiranju vam lahko zdravilo Respreeza daje negovalec ali si ga dajete sami, vendar le po ustreznem usposabljanju.
Suspected allergic or anaphylactic type reactions may require immediate discontinuation of the infusion, depending on the nature and severity of the reaction.
Ob sumu na reakcije alergijske ali anafilaktične vrste bo morda treba z infundiranjem takoj prenehati, odvisno od narave in resnosti reakcije.
Do no stop using this medicine without consulting your doctor or healthcare professional.
Če ste prenehali uporabljati zdravilo Respreeza Tega zdravila ne prenehajte uporabljati, ne da bi se posvetovali z zdravnikom ali zdravstvenim delavcem.
Gently swirl the Respreeza vial until the powder is completely dissolved (Figure 6).
Nežno obračajte vialo z zdravilom Respreeza dokler se prašek povsem ne raztopi (slika 6).
Human alpha1-proteinase inhibitor has a molecular weight of 51 kDa and belongs to the family of serine protease inhibitors.
Humani zaviralec alfa1proteinaze ima molekulno maso 51 kDa in sodi v družino zaviralcev serinske proteaze.
• Bend the entire Mix2Vial set to the side until it disconnects from the Respreeza vial (Figure 5).
• Upognite celoten komplet Mix2Vial na stran dokler se ne odstrani iz viale z zdravilom Respreeza (slika 5).
Following the completion of the RAPID study, an analysis of achieved median alpha1-proteinase inhibitor levels and lung density decline was conducted.
Po dokončanju študije RAPID so izvedli analizo dosežene mediane ravni zaviralca alfa1-proteinaze in upada pljučne gostote.
What Respreeza looks like and contents of the pack
Izgled zdravila Respreeza in vsebina pakiranja
A total of 180 subjects with alpha1-proteinase inhibitor deficiency characterized by a serum alpha1-proteinase inhibitor level < 11 μM (i.e. < 50 mg/dL as determined by nephelometry) and clinical evidence of emphysema, were randomized to receive a weekly 60 mg / kg bw intravenous dose of either Respreeza (93 subjects) or placebo (87 subjects) for up to 24 months.
Skupaj 180 oseb s pomanjkanjem zaviralca alfa1-proteinaze, za katerega so značilne ravni zaviralca proteinaze alfa1 v serumu < 11 μM (tj. < 50 mg/dl, kar se določi z nefelometrijo) in kliničnimi znaki emfizema, je bilo randomiziranih za prejemanje tedensko 60 mg/kg telesne mase intravenskega odmerka bodisi zdravila Respreeza (93 oseb) ali placeba (87 oseb) do 24 mesecev.
Ensure that the Respreeza vial and water for injections vial are at room temperature (up to 25°C).
Poskrbite, da sta viala z zdravilom Respreeza in viala z vodo za injekcije sobne temperature (do 25 °C).
Table 1: Pharmacokinetic parameters for alpha1-proteinase inhibitor following a single 60 mg / kg bw dose of Respreeza Pharmacokinetic Parameter
Preglednica 1: Farmakokinetični parametri za zaviralca alfa1-proteinaze, ki mu sledi en 60 mg/kg telesne mase odmerek zdravila Respreeza Farmakokinetični parametri
The solution should be infused at an infusion rate of about 0.08 ml per kg body weight each min, as determined by your response and your comfort.
Raztopino morate infundirati s hitrostjo infundiranja približno 0,08 ml na kg telesne mase vsako minuto, kot je bilo ugotovljeno glede na vaš odziv in vaše stanje.
The subjects ranged in age from 31 to 67 years (median age 54 years) with average baseline alpha1-proteinase inhibitor levels of approximately 6.15 µM, and average volume-adjusted CT lung density of 47 g/L / 50 g/L for Respreeza and placebo subjects, respectively.
Osebe so bile stare od 31 do 67 let (mediana starost 54 let) s povprečnimi izhodiščnimi ravnmi zaviralca alfa1-proteinaze približno 6,15 µM in povprečno za volumen prilagojeno gostoto pljuč na CT 47 g/l za osebe na zdravilu Respreeza in 50 g/l za osebe na placebu.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped hepatitis A (HAV) and parvovirus B19 virus.
Uvedeni ukrepi veljajo za učinkovite proti virusom z ovojnico, kot so virus humane imunske pomanjkljivosti (HIV), virus hepatitisa B (HBV) in virus hepatitisa C (HCV) in proti virusom brez ovojnice, kot sta virus hepatitisa A (HAV) in parvovirus B19.
Respreeza-treated subjects demonstrated a consistent pattern of slower lung density decline than those receiving placebo (see Figure 1).
Osebe, zdravljene z zdravilom Respreeza, so imele dosledni vzorec počasnejšega upadanja pljučne gostote, kot osebe, ki so prejemale placebo (glejte sliko 1).
Depending on the nature and severity of the reaction, your doctor or healthcare professional may decide whether to slow or stop the administration completely and give appropriate treatment for the reaction.
Odvisno od narave in resnosti reakcije se lahko zdravnik ali zdravstveni delavec odloči za upočasnitev ali popolno ustavitev infundiranja in dajanje ustreznega zdravljenja za reakcijo.
Depending on the nature and severity of the reaction, your doctor may decide whether to slow or stop the infusion completely and start the appropriate treatment.
Odvisno od narave in resnosti reakcije se lahko zdravnik odloči za upočasnitev ali popolno ustavitev infundiranja in uvedbo ustreznega zdravljenja.
Prime the chamber by squeezing the drip chamber until Respreeza has filled the chamber half-way.
Napolnite komoro, tako da stiskate kapalno komoro, dokler zdravilo Respreeza komore ne napolni do polovice.
No animal fertility studies have been conducted with Respreeza and its effect on human fertility has not been established in controlled clinical trials.
Študij razmnoževanja pri živalih z zdravilom Respreeza niso opravili, zato učinek na plodnost pri ljudeh ni bil ugotovljen v nadzorovanih kliničnih preskušanjih.
Make sure that the roller clamp on the administration set is closed.
Prepričajte se, da je stišček na pripomočku za infundiranje zaprt.
Paediatric Population Safety and effectiveness in the paediatric population have not been established.
Varnost in učinkovitost zdravila Respreeza pri pediatrični populaciji nista bili dokazani.
You may be allergic to human alpha1-proteinase inhibitor even if you have previously received human alpha1-proteinase inhibitors and had tolerated them well.
Morda ste alergični na humani zaviralec alfa1-proteinaze, tudi če ste pred tem že prejemali humani zaviralec alfa1-proteinaze in ste ga dobro prenašali.
Any unused medicinal product or waste material should be disposed as instructed by your doctor or healthcare professional.
Neuporabljeno zdravilo ali odpadni material zavrzite v skladu z navodili zdravnika ali zdravstvenega delavca.
Discard the water for injections vial with the entire Mix2Vial set.
Zavrzite vialo z vodo za injekcije s celotnim kompletom Mix2Vial.
However, despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded.
Vendar pa kljub tem ukrepom pri uporabi zdravil, pripravljenih iz človeške krvi ali plazme, ni mogoče povsem izključiti prenosa okužb.
Normal healthy individuals produce sufficient alpha1-proteinase inhibitor to control the NE produced by activated neutrophils and are thus able to prevent inappropriate proteolysis of lung tissue by NE.
Pri normalnih zdravih posameznikih nastaja dovolj zaviralca alfa1proteinaze za nadzor NE, ki ga tvorijo aktivirani nevtrofilci, zato lahko preprečijo neustrezno proteolizo pljučnega tkiva zaradi NE.
It is unknown whether Respreeza / metabolites are excreted in human milk.
Ni znano, ali se zdravilo Respreeza/njegovi presnovki izločajo v materino mleko.
The RAPID extension study demonstrated that the reduced rate in lung density decline was maintained for subjects continuously treated with Respreeza for 4 years (see Figure 1).
Podaljšek študije RAPID je pokazal, da se je počasnejše zmanjševanje pljučne gostote pri preiskovancih, ki so se 4 leta neprekinjeno zdravili z zdravilom Respreeza, ohranilo (glejte sliko 1).
The safety and efficacy of Respreeza in elderly patients (65 years of age or older) have not been established in specific clinical trials.
Varnost in učinkovitost zdravila Respreeza pri starejših bolnikih (starih 65 let ali več) nista bili dokazani v specifičnih kliničnih preskušanjih.
Since human alpha1-proteinase inhibitor is a protein and a physiological constituent of human blood, it is not expected to present carcinogenic, genotoxic, or teratogenic effects.
Ker je humani zaviralec alfa1proteinaze beljakovina in fiziološka sestavina krvi pri človeku, se kancerogeni, genotoksični ali teratogeni učinki ne pričakujejo.
Dizziness may occur following the administration of Respreeza (see section 4.8).
Po dajanju zdravila Respreeza se lahko pojavi omotica (glejte poglavje 4.8).
This medicine contains the active substance human alpha1-proteinase inhibitor, which is a normal component of the blood and is found in the lung.
To zdravilo vsebuje učinkovino humani zaviralec alfa1-proteinaze, ki je normalna sestavina krvi in se najde v pljučih.
Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards.
Previdno odstranite pretisni omot s kompleta Mix2Vial, tako da jo primete za obod in potegnete navpično navzgor.
Excipients with known effect Respreeza contains approximately 1.9 mg sodium per ml of reconstituted solution (81 mmol/l).
Pomožne snovi z znanim učinkom Zdravilo Respreeza vsebuje približno 1,9 mg natrija na ml rekonstituirane raztopine (81 mmol/l).
Elevate the administration container (if intravenous bag, hang on an intravenous pole).
Dvignite vsebnik za apliciranje (v primeru intravenske vrečke jo obesite na stojalo za infuzijo).
The safety and efficacy of Respreeza in the paediatric population (below 18 years) have not been established.
Varnost in učinkovitost zdravila Respreeza pri pediatrični populaciji (stari do 18 let) nista bili dokazani.
What Respreeza is and what it is used for
Kaj je zdravilo Respreeza in za kaj ga uporabljamo
Human alpha1-proteinase inhibitor is understood to be the primary anti-protease in the lower respiratory tract, where it inhibits neutrophil elastase (NE).
Predvideva se, da je humani zaviralec alfa1-proteinaze primarna proti-proteaza v spodnjih dihalih, kjer zavira nevtrofilno elastazo (NE).
This medicine is used in adults with known severe alpha1-proteinase inhibitor deficiency (an inherited condition also called alpha1 antitrypsin deficiency) who have developed a lung condition called emphysema.
To zdravilo se uporablja pri odraslih z znanim hudim pomanjkanjem zaviralca alfa1-proteinaze (podedovana bolezen, ki se imenuje tudi pomanjkanje alfa1 antitripsina), pri katerih se je razvila bolezen pljuč, imenovana emfizem.
Hypersensitivity reactions may occur, including in patients who have tolerated previous treatment with human alpha1-proteinase inhibitor.
Pojavijo se lahko preobčutljivostne reakcije, tudi pri bolnikih, ki so predhodno zdravljenje s humanimi zaviralci alfa1-proteinaze prenašali.
The recommended dose is 60 mg per kg of body weight and should be administered once per week.
Priporočeni odmerek je 60 mg na kg telesne mase in se daje enkrat na teden.
One vial contains approximately 1,000 mg, 4,000 mg or 5,000 mg of alpha1-proteinase inhibitor.
Ena viala vsebuje približno 1.000 mg, 4.000 mg ali 5.000 mg zaviralca alfa1-proteinaze.
The mean trough serum alpha1-proteinase inhibitor levels at steady state (Weeks 7-11) were maintained above 11 M.
Povprečne najnižje ravni zaviralca alfa1proteinaze v serumu v stanju dinamičnega ravnovesja (tedni 7 do 11) so se ohranile nad 11 M.
• With the other hand tightly grasp the water for injections vial and the blue part of the Mix2Vial set.
• Z drugo roko močno primite vialo z vodo za injekcije in modri del kompleta Mix2Vial.
Such side effects may occur even if you previously received human alpha1-proteinase inhibitors and had tolerated them well.
Taki neželeni učinki se lahko pojavijo celo, če ste predhodno že prejemali humani zaviralec alfa1proteinaze in ste ga dobro prenašali.
Respreeza should only be administered intravenously by infusion after reconstitution.
Zdravilo Respreeza se lahko daje le v obliki intravenske infuzije po rekonstituciji.
The safety and efficacy of Respreeza in elderly patients (65 years of age or older) have not been established in clinical trials.
Varnost in učinkovitost zdravila Respreeza pri starejših bolnikih (starih 65 let ali več) nista bili dokazani v kliničnih preskušanjih.
How to use Respreeza
Kako uporabljati zdravilo Respreeza
CSL Behring GmbH, 35041 Marburg, Germany
CSL Behring GmbH, 35041 Marburg, Nemčija
Your doctor will inform you about signs of allergic reactions (for example chills, flushing, faster heartbeat, fall in blood pressure, light-headedness, rash, hives, itching, difficulty in breathing or swallowing as well as swelling of your hands, face, or mouth) (see also section 4).
Zdravnik vas bo obvestil o znakih alergijske reakcije (na primer mrzlica, vročinski oblivi, hitrejši srčni utrip, padec krvnega tlaka, vrtoglavica, izpuščaj, koprivnica, srbenje, težave z dihanjem ali požiranjem ter otekanje rok, obraza ali ust) (glejte tudi poglavje 4).
The model predicted mean steady-state concentration was 21.8 µM after a 60 mg /kg bw / week dose.
Z modelom je bila napovedana povprečna koncentracija v stanju dinamičnega ravnovesja 21,8 µM po odmerku 60 mg/kg telesne mase/teden.
Use aseptic technique to transfer the reconstituted solutions into the administration container (e.g., empty intravenous bag or glass bottle; (not supplied) via a commercially available intravenous fluid tubing transfer set (not supplied)).
Z aseptično tehniko prenesite rekonstituirano raztopino v vsebnik za apliciranje (npr. v prazno intravensko vrečo ali steklenico (ni priloženo); z intravenskim cevnim setom za prenos, ki ga kupite (ni priloženo)).
Do not remove the Mix2Vial set from the blister package.
Ne odstranite kompleta Mix2Vial iz pretisnega omota.
First infusions should be administered under the supervision of a healthcare professional experienced in the treatment of alpha1-proteinase inhibitor deficiency.
Prve infuzije je treba dati pod nadzorom zdravstvenega delavca z izkušnjami v zdravljenju pomanjkanja zaviralca alfa1-proteinaze.
After reconstitution, the solution should be used immediately.
Pripravljeno raztopino je treba uporabiti takoj.
After it has been reconstituted with water for injections, the solution should be clear, colourless to slightly yellow and free from visible particles.
Po rekonstituciji z vodo za injekcije mora biti raztopina bistra, brezbarvna do rahlo rumenkasta in brez vidnih delcev.
Open the Mix2Vial set by peeling off the lid (Figure 1).
Odprite komplet Mix2Vial tako, da odlepite pokrov (slika 1).
Human alpha1-proteinase inhibitor is a normal constituent of human blood.
Humani zaviralec alfa1-proteinaze je normalna sestavina človeške krvi.
This analysis revealed an inverse linear relationship between trough serum alpha1-proteinase inhibitor levels and the annual decline in lung density as measured by volume adjusted CT scans for subjects receiving 60 mg / kg bw intravenous dose of Respreeza.
Ta analiza je pokazala inverzno linearno razmerje med najnižjimi ravnmi zaviralca alfa1-proteinaze v serumu in letnim upadom pljučne gostote, izmerjene s slikami CT, prilagojenimi za volumen, za osebe, ki so prejemale intravenski odmerek zdravila Respreeza 60 mg/kg telesne mase.
The total protein content is approximately 5,500 mg per vial.
Skupna vsebnost beljakovine je približno 5.500 mg na vialo.
Remove the plastic flip-top cap from the water for injections vial.
Odstranite plastično zunanjo zaščitno zaporko z viale z vodo za injekcije.
Blood and lymphatic system disorders
Bolezni krvi in limfatičnega sistema bolečine v bezgavki
System Organ Class (SOC)
Organski sistem (OS)
Place the water for injections vial on an even, clean surface and hold the vial tight.
Postavite vialo z vodo za injekcije na ravno, čisto podlago in jo trdno držite.
• if you are allergic to human alpha1-proteinase inhibitor or any of the other ingredients of this medicine (listed in section 6).
• če ste alergični na humani zaviralec alfa1-proteinaze ali katero koli sestavino tega zdravila
After reconstitution, Respreeza is given by infusion into a vein.
Po rekonstituciji se zdravilo Respreeza infundira v žilo.
The mean (Standard Deviation) of the steady state trough serum alpha1-proteinase inhibitor level for Respreeza-treated subjects was 17.7 M (2.5).
Povprečna (standardni odklon) najnižja raven zaviralca alfa1-proteinaze v serumu v stanju dinamičnega ravnovesja pri osebah, zdravljenih z zdravilom Respreeza, je bila 17,7 M (2,5).