FrancophonIA/ELRC3.0 huggingface dataset:
English: • pain in the stomach area under the ribs (upper abdominal pain)
Croatian: • bol u području trbuha, ispod rebara (bol u gornjem dijelu abdomena)
English: Your doctor will test your blood every month for the first year of treatment and at regular intervals after that.
Croatian: Liječnik će provoditi krvne pretrage svaki mjesec tijekom prvih godinu dana liječenja i u redovitim razmacima nakon toga.
English: Symptoms of overdose are not established and there is no specific treatment in the event of Lynparza overdose.
Croatian: Nisu utvrđeni simptomi predoziranja i nema specifičnog liječenja u slučaju predoziranja lijekom Lynparza.
English: PARP inhibitors can destroy cancer cells that are not good at repairing DNA damage.
Croatian: Inhibitori PARP-a mogu uništiti stanice raka koje ne mogu uspješno popraviti oštećenje DNK.
English: Overall disease classification Metastatic
Croatian: Općenita klasifikacija bolesti Metastatska
English: There are no clinical data on fertility.
Croatian: Nema kliničkih podataka o utjecaju na plodnost.
English: There were no confirmed responses in the comparator arm.
Croatian: U usporednoj skupini nije zabilježen nijedan potvrđen odgovor.
English: • looking for faulty DNA repair genes, such as BRCA (BReast CAncer) genes.
Croatian: • traženjem neispravnih gena za popravak DNK, kao što su geni BRCA ('BReast CAncer gene'
English: What Lynparza contains
Croatian: Što Lynparza sadrži
English: Age - year (median)
Croatian: Dob -godine (medijan)
English: Effect of other medicinal products on olaparib
Croatian: Učinak drugih lijekova na olaparib
English: All patients
Croatian: Sve bolesnice
English: The major primary target organ for toxicity in both species was the bone marrow, with associated changes in peripheral haematology parameters.
Croatian: Glavni primarni ciljni organ za toksičnost kod obje je vrste bila koštana srž, a primijećene su i s time povezane promjene hematoloških parametara u perifernoj krvi.
English: Lynparza tablets may be taken without regard to meals.
Croatian: Lynparza tablete mogu se uzimati bez obzira na obroke.
English: Therefore, an additional non-hormonal contraceptive method should be considered during treatment (see section 4.5).
Croatian: Stoga, tijekom liječenja treba razmotriti dodatne nehormonske metode kontracepcije (vidjeti dio 4.5).
English: Patients who experience these symptoms should observe caution when driving or using machines.
Croatian: Bolesnici koji primijete te simptome trebaju biti oprezni dok upravljaju vozilom ili rade sa strojevima.
English: If preferred, you can keep Lynparza capsules out of the refrigerator (below 30°C) for up to 3 months.
Croatian: Ako želite, Lynparza kapsule možete čuvati izvan hladnjaka (na temperaturi ispod 30°C) do 3 mjeseca.
English: Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous treatment, can be treated beyond 2 years.
Croatian: Bolesnice kod kojih su nakon 2 godine prisutni dokazi bolesti i koje prema mišljenju nadležnog liječnika mogu ostvariti daljnju korist od nastavka liječenja, mogu se liječiti i dulje od 2 godine.
English: Pharmacotherapeutic group: antineoplastic agents, other antineoplastic agents, ATC code: L01XX46
Croatian: Farmakoterapijska skupina: antineoplastici, ostali antineoplastici, ATK oznaka: L01XX46
English: The safety and efficacy of Lynparza in children and adolescents have not been established.
Croatian: Sigurnost i djelotvornost lijeka Lynparza kod djece i adolescenata nisu ustanovljene.
English: • Take Lynparza at least one hour after eating food.
Croatian: • Uzmite lijek Lynparza najmanje jedan sat nakon obroka.
English: Alu/Alu non-perforated blister containing 8 film-coated tablets.
Croatian: Al/Al neperforirani blister koji sadrži 8 filmom obloženih tableta.
English: No adjustment in starting dose is required for elderly patients.
Croatian: Nije potrebno prilagođavati početnu dozu kod starijih bolesnika.
English: Frequencies of occurrence of adverse reactions are defined as: very common (≥ 1/10); common ( 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); not known (cannot be estimated from available data).
Croatian: Učestalost pojave nuspojava definirana je kao: vrlo često (≥ 1/10); često ( 1/100 i < 1/10); manje često (≥ 1/1000 i < 1/100); rijetko (≥ 1/10 000 i < 1/1000); vrlo rijetko (< 1/10 000); nepoznato (ne može se procijeniti iz dostupnih podataka).
English: Genetic testing should be conducted by an experienced laboratory using a validated test.
Croatian: Genetičko testiranje mora se provoditi u iskusnom laboratoriju primjenom validiranog testa.
English: • protease inhibitors boosted with ritonavir or cobicistat, boceprevir, telaprevir, nevirapine,
Croatian: • inhibitore proteaze pojačane ritonavirom ili kobicistatom, boceprevir, telaprevir, nevirapin,
English: 56 film-coated tablets (7 blisters).
Croatian: 56 filmom obloženih tableta (7 blistera).
English: Also, some other medicines can affect the way Lynparza works.
Croatian: Isto tako neki drugi lijekovi mogu utjecati na način djelovanja lijeka Lynparza.
English: • Swallow Lynparza tablets whole, with or without food.
Croatian: • Lynparza tablete progutajte cijele, s hranom ili bez nje.
English: What Lynparza looks like and contents of the pack
Croatian: Kako Lynparza izgleda i sadržaj pakiranja
English: • sore mouth (stomatitis).
Croatian: • upala sluznice usta (stomatitis)
English: The majority of the metabolism was attributable to oxidation reactions with a number of the components produced undergoing subsequent glucuronide or sulfate conjugation.
Croatian: Glavnina metabolizma mogla se pripisati oksidacijskim reakcijama, nakon kojih je određen broj novonastalih komponenti prošao kroz glukuronidnu ili sulfatnu konjugaciju.
English: The potential for olaparib to induce CYP2C9, CYP2C19 and P-gp can also not be excluded.
Croatian: Također se ne može isključiti potencijal olapariba za indukciju CYP2C9, CYP2C19 i P-gp-a također se ne može se isključiti.
English: months n-olaparib 74 n-placebo
Croatian: mjeseci n-olaparib n-placebo
English: • increase in blood creatinine - this test is used to check how your kidneys are working.
Croatian: • povišena razina kreatinina u krvi - tom se pretragom provjerava kako rade bubrezi
English: Do not take Lynparza:
Croatian: Nemojte uzimati lijek Lynparza:
English: Lynparza tablets should be swallowed whole and not chewed, crushed, dissolved or divided.
Croatian: Lynparza tablete treba progutati cijele te se ne smiju žvakati, drobiti, rastapati ni lomiti.
English: AstraZeneca UK Limited Silk Road Business Park Macclesfield, Cheshire, SK10 2NA United Kingdom
Croatian: AstraZeneca UK Limited Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA Ujedinjeno Kraljevstvo
English: What Lynparza is and what it is used for What you need to know before you take Lynparza How to take Lynparza
Croatian: Što je Lynparza i za što se koristi Što morate znati prije nego počnete uzimati lijek Lynparza Kako uzimati lijek Lynparza
English: events/patients
Croatian: događaji/bolesnice
English: The capsules must be discarded after this period.
Croatian: Nakon tog razdoblja, kapsule se moraju odbaciti.
English: For patients who remained in complete clinical response (i.e. no radiological evidence of disease), the maximum duration of treatment was 2 years; however, patients who had evidence of disease that remained stable (i.e. no evidence of disease progression) could continue to receive Lynparza beyond 2 years.
Croatian: Kod bolesnica u kojih se održao potpuni klinički odgovor (tj. kod kojih nije bilo radioloških dokaza bolesti) maksimalno trajanje liječenja iznosilo je 2 godine; međutim, bolesnice kod kojih su postojali dokazi stabilne bolesti (tj. kod kojih nije bilo dokaza progresije bolesti) mogle su nastaviti primati lijek Lynparza i nakon 2 godine.
English: Therefore, olaparib upon co-administration may reduce the exposure to substrates of these metabolic enzymes and transport protein.
Croatian: Stoga, istodobna primjena olapariba mogla bi smanjiti izloženost supstratima tih metaboličkih enzima i transportnih proteina.
English: Table 7 Patient demographic and baseline characteristics in OlympiAD
Croatian: Tablica 7 Demografske i početne značajke bolesnika u ispitivanju OlympiAD
English: It is also not recommended to consume grapefruit juice while on Lynparza therapy as it is a CYP3A inhibitor.
Croatian: Također se ne preporučuje konzumirati sok od grejpa tijekom terapije lijekom Lynparza jer je on inhibitor CYP3A.
English: efavirenz - used for viral infections, including HIV
Croatian: efavirenz - koriste se za liječenje virusnih infekcija, uključujući HIV
English: TFST Time from randomisation to start of first subsequent therapy or death.
Croatian: vrijeme od randomizacije do početka prve sljedeće terapije ili smrti.
English: • any other anticancer medicines
Croatian: • bilo koji drugi lijek za liječenje raka
English: The incidence of anaemia adverse reactions was 22.8% (CTCAE grade ≥3 7.4%).
Croatian: Incidencija nuspojave anemije bio je 22,8% (stupanj ≥3 7,4%).
English: Chemotherapy (N = 97) Olaparib 300 mg twice daily (N = 205)
Croatian: Kemoterapija (N = 97) Olaparib 300 mg dvaput na dan (N = 205)
English: The metabolism of olaparib is extensive.
Croatian: Metabolizam olapariba je opsežan.
English: The median follow-up time in censored patients was 25.3 months for olaparib versus 26.3 months for comparator.
Croatian: Medijan praćenja kod cenzuriranih bolesnika iznosio je 25,3 mjeseca za olaparib u odnosu na 26,3 mjeseca za usporednu terapiju.
English: Ninety three percent (93%) of patients were randomised within 8 weeks of their last dose of platinum-based chemotherapy.
Croatian: Devedeset i tri posto (93%) bolesnica randomizirano je unutar 8 tjedana od posljednje doze kemoterapije utemeljene na platini.
English: In patients with mutations (changes) in certain genes called BRCA (breast cancer gene), who are at risk of developing some forms of cancer, PARP inhibitors are able to trigger the death of cancer cells by blocking an enzyme that helps repair DNA.
Croatian: U bolesnica s mutacijama (promjenama) u određenim genima zvanima BRCA ('BReast CAncer gene', gen za rak dojke) koje imaju rizik za razvoj određenih oblika raka, inhibitori PARP-a mogu potaknuti smrt stanica raka blokirajući enzim koji pomaže u popravku DNK.
English: Patients had tumour assessments at baseline and every 12 weeks for 3 years, and then every 24 weeks relative to date of randomisation, until objective radiological disease progression.
Croatian: Kod bolesnika je provedena tumorska ocjena na početku ispitivanja te svakih 12 tjedna tijekom 3 godine, a zatim svaka 24 tjedna u odnosu na datum randomizacije, sve do objektivne radiološke progresije bolesti.
English: Confirmed responses (by BICR) were defined as a recorded response of either CR/PR, confirmed by repeat imaging not less than 4 weeks after the visit when the response was first observed.
Croatian: Potvrđen odgovor (prema ocjeni BICR-a) definirao se kao zabilježen potpuni ili djelomični odgovor, potvrđen ponovljenim oslikavanjem provedenim najmanje 4 tjedna nakon posjeta tijekom kojeg je odgovor prvi put opažen.
English: Your doctor has prescribed Lynparza capsules for you.
Croatian: Liječnik Vam je propisao Lynparza kapsule.
English: Dose interruptions occurred most frequently in the first 3 months and dose reductions in the first 3-6 months of treatment.
Croatian: Privremeni prekidi doziranja pojavili su se najčešće u prva tri mjeseca a smanjenje doziranja u prva 3-6 mjeseci liječenja.
English: España AstraZeneca Farmacéutica Spain, S.A.
Croatian: AstraZeneca Farmacéutica Spain, S.A.
English: What Lynparza is and how it works
Croatian: Što je Lynparza i kako djeluje
English: Do not take Lynparza if any of the above apply to you.
Croatian: Nemojte uzimati lijek Lynparza ako se nešto od navedenoga odnosi na Vas.
English: Probability of progression free survival
Croatian: Vjerojatnost preživljenja bez progresije bolesti
English: Olaparib is a type of cancer medicine called a PARP inhibitor (poly [adenosine diphosphate-ribose] polymerase inhibitor).
Croatian: Olaparib je vrsta lijeka za liječenje raka koja se naziva inhibitorom PARP-a (inhibitor poli [adenozin difosfat-riboza] polimeraze).
English: However, no dose adjustment is required on the basis of ethnicity (see section 5.2).
Croatian: Međutim, nije potrebno prilagođavati dozu s obzirom na etničko podrijetlo (vidjeti dio 5.2).
English: BRCA mutation status should be determined by an experienced laboratory using a validated test method (see section 5.1).
Croatian: Status mutacije BRCA gena mora se odrediti u iskusnom laboratoriju primjenom validirane metode (vidjeti dio 5.1).
English: The recommended Lynparza monotherapy dose is not suitable for combination with myelosuppressive anticancer medicinal products.
Croatian: Preporučena doza lijeka Lynparza u monoterapiji nije prikladna za kombinaciju s mijelosupresivnim lijekovima za liječenje karcinoma.
English: • methotrexate - used to treat cancer, rheumatoid arthritis and psoriasis.
Croatian: • metotreksat - koristi se za liječenje raka, reumatoidnog artritisa i psorijaze
English: Efficacy results are presented in Table 2 and Figures 1 and 2.
Croatian: Rezultati za djelotvornost prikazani su u Tablici 2 te na Slikama 1 i 2.
English: The analysis was performed using a Cox proportional hazards model with factors for treatment, ethnic descent, platinum sensitivity and response to final platinum therapy.
Croatian: Analiza je provedena uz primjenu Coxova modela proporcionalnog hazarda s faktorima za liječenje, etničko podrijetlo, osjetljivost na platinu i odgovor na posljednju terapiju platinom.
English: Effect of olaparib on other medicinal products
Croatian: Učinak olapariba na druge lijekove
English: See section 2 “Information on other ingredients in this medicine”.
Croatian: Pogledajte dio 2. Informacije o drugim sastojcima lijeka.
English: The secondary endpoints TFST and PFS2 demonstrated a persistent and statistically significant improvement for olaparib compared with placebo (Table 4).
Croatian: Sekundarne mjere ishoda TFST i PFS2 pokazale su kontinuirano i statistički značajno poboljšanje za olaparib u usporedbi sa placebom (Tablica 4).
English: Depending on the test used and the international classification consensus, the BRCA1/2 mutations have been classified as deleterious/suspected deleterious or pathogenic/likely pathogenic.
Croatian: Ovisno o upotrijebljenom testu i usuglašenoj međunarodnoj klasifikaciji, mutacije gena BRCA1/2 klasificirale su se kao štetne/suspektne štetne mutacije ili patogene/vjerojatno patogene mutacije.
English: Elimination Following a single dose of
Croatian: Nakon jednokratne doze
English: In rats, minimal degenerative effects on gastrointestinal tract were also noted.
Croatian: Kod štakora su primijećeni i minimalni degenerativni učinci na probavni sustav.
English: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity.
Croatian: Preporučuje se nastaviti liječenje do progresije osnovne bolesti ili pojave neprihvatljive toksičnosti.
English: Lynparza is provided in HDPE plastic bottles containing 112 hard capsules.
Croatian: Lynparza dolazi u plastičnim HDPE bocama koje sadrže 112 tvrdih kapsula.
English: Patients in the olaparib group continued to receive treatment longer than those in the placebo group.
Croatian: Bolesnice u skupini liječenoj olaparibom nastavile su primati liječenje dulje od onih u skupini koja je primala placebo.
English: In Study 19, 20 patients were identified with a somatic tumour BRCA mutation (a mutation in the tumour but wildtype in the germline).
Croatian: U ispitivanju 19, kod 20 bolesnica je nađena somatska tumorska BRCA mutacija (mutacija u tumoru ali divlji tip germinativno).
English: • you are taking certain medicines that may affect Lynparza (see section 2).
Croatian: • ako uzimate određene lijekove koji mogu utjecati na lijek Lynparza (pogledajte dio 2.)
English: BRCA1/2 wt/VUS
Croatian: Bolesnice s BRCA1/2 wt/VUS
English: Clinical studies of olaparib in combination with other anticancer medicinal products, including DNA damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.
Croatian: Klinička ispitivanja olapariba u kombinaciji s drugim lijekovima za liječenje karcinoma, uključujući lijekove koji oštećuju DNK, ukazuju na jačanje i produljenje mijelosupresivne toksičnosti.
English: Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Croatian: Liječenje lijekom Lynparza mora započeti i nadzirati liječnik s iskustvom u primjeni lijekova za liječenje karcinoma.
English: This clastogenicity is consistent with the known pharmacology of olaparib and indicates potential for genotoxicity in man.
Croatian: Ta je klastogenost u skladu s poznatom farmakologijom olapariba te ukazuje na potencijalnu genotoksičnost kod ljudi.
English: Retreatment with olaparib was not permitted following progression on olaparib.
Croatian: Ponovno liječenje olaparibom nije bilo dopušteno nakon progresije na olaparibu.
English: • rifampicin, rifapentine, rifabutin - used for bacterial infections, including tuberculosis (TB)
Croatian: • rifampicin, rifapentin, rifabutin - koriste se za liječenje bakterijskih infekcija, uključujući tuberkulozu (TBC)
English: gBRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method.
Croatian: Status gBRCA1/2 mutacija mora se odrediti u iskusnom laboratoriju primjenom validirane metode testiranja.
English: If you forget to take Lynparza
Croatian: Ako ste zaboravili uzeti lijek Lynparza
English: Consequently, Lynparza may be taken without regard to food (see section 4.2).
Croatian: Stoga se Lynparza može uzimati neovisno o hrani (vidjeti dio 4.2).
English: The most common histological type was serous (> 90%), endometrioid histology was reported in 6% of the patients.
Croatian: Najčešći histološki tip je bio serozni (> 90%), endometrioidni je zabilježen u 6% bolesnika.
English: Patients could have received prior bevacizumab, except in the regimen immediately prior to randomisation.
Croatian: Bolesnice su mogle ranije biti liječene bevacizumabom, osim u protokolu primijenjenom neposredno prije randomizacije.
English: Gastrointestinal toxicities
Croatian: Gastrointestinalna toksičnost
English: Secondary efficacy endpoints included PFS2; OS, TDT, TFST, TSST; and HRQoL.
Croatian: Sekundarne mjere ishoda za djelotvornost uključivale su PFS2; OS, TDT, TFST, TSST i HRQoL.
English: • feeling short of breath, feeling very tired, pale skin or fast heart beat - these may be symptoms of a decrease in the number of red blood cells (anaemia).
Croatian: • nedostatak zraka, izrazit umor, blijeda koža ili ubrzani otkucaji srca - to mogu biti simptomi sniženog broja crvenih krvnih stanica (anemija)
English: If you are planning to breast-feed, tell your doctor.
Croatian: Ako planirate dojiti, obavijestite o tome svog liječnika.
English: You should have received chemotherapy medicines either before or after your cancer has spread.
Croatian: Da biste primali ovaj lijek, morali ste prethodno primati kemoterapiju, bilo prije ili nakon širenja raka.
English: (See previous paragraph: “Women of childbearing potential/contraception in females” for further information about birth control and pregnancy testing.)
Croatian: (Za više informacija o kontracepciji i testiranju na trudnoću vidjeti prethodni odlomak 'Žene reproduktivne dobi/kontracepcija kod žena'.)
English: The magnitude of the effect of moderate to strong inducers (e.g. efavirenz, rifabutin) on olaparib exposure is not established, therefore the co-administration of Lynparza with these medicinal products is also not recommended (see section 4.4).
Croatian: Opseg učinka umjerenih do snažnih induktora (npr. efavirenz, rifabutin) na izloženost olaparibu nije ustanovljen, stoga se ne preporučuje ni istodobna primjena lijeka Lynparza s tim lijekovima (vidjeti dio 4.4).
English: Missing Number of prior lines of chemotherapy for metastatic breast cancer (%)
Croatian: Broj prethodnih linija kemoterapije za metastatski rak dojke (%)
English: Consistent results were observed in the subgroups of patients by evidence of the disease at study entry.
Croatian: Opaženi su dosljedni rezultati u podskupinama bolesnica definiranima prema dokazu bolesti pri uključivanju u ispitivanje.
English: Treatment was continued until radiological progression of the underlying disease, unacceptable toxicity or for up to 2 years.
Croatian: Liječenje se nastavilo do radiološke progresije osnovne bolesti, pojave neprihvatljive toksičnosti ili do 2 godine.
English: Detection of BRCA mutation
Croatian: Detekcija mutacija BRCA gena
English: Do not eat preferably for up to 2 hours after taking Lynparza.
Croatian: Nemojte jesti po mogućnosti do 2 sata nakon uzimanja lijeka Lynparza.
English: Lynparza is supplied in packs containing 56 film-coated tablets (7 blisters of 8 tablets each), or multipacks containing 112 (2 packs of 56) film-coated tablets.
Croatian: Lynparza dolazi u pakiranjima koja sadrže 56 filmom obloženih tableta (7 blistera od kojih svaki sadrži 8 tableta), ili u višestrukim pakiranjima koja sadrže 112 (2 pakiranja od 56) filmom obloženih tableta.
English: Your doctor has prescribed Lynparza film-coated tablets for you.
Croatian: Liječnik Vam je propisao Lynparza filmom obložene tablete.
English: HDPE plastic bottle with a child-resistant closure containing 112 hard capsules.
Croatian: Plastična HDPE boca sa zatvaračem sigurnim za djecu, koja sadrži 112 tvrdih kapsula.
English: Olaparib showed no mutagenic potential, but was clastogenic in mammalian cells in vitro.
Croatian: Olaparib nije pokazao mutageni potencijal, ali je bio klastogen u stanicama sisavaca in vitro.
English: • Your doctor will tell you how many tablets of Lynparza to take.
Croatian: • Liječnik će Vam reći koliko tableta lijeka Lynparza trebate uzeti.
English: Lynparza is used for the treatment of:
Croatian: Lynparza se koristi za liječenje:
English: Absence of fully functional HRR pathway is one of the key determinants of platinum sensitivity in ovarian and other cancers.
Croatian: Nepostojanje potpuno funkcionalnog puta kojim se odvija popravak homolognom rekombinacijom jedna je od ključnih odrednica osjetljivosti na platinu kod karcinoma jajnika i drugih karcinoma.
English: In the absence of BRCA1 or BRCA2 mutations, HRR pathway may be compromised by other mechanisms, although the causative aberrancy and penetrance are not fully elucidated.
Croatian: Ako nema mutacija BRCA1 ili BRCA2, popravak homolognom rekombinacijom mogu ometati i drugi mehanizmi, iako uzročna aberacija i penetrantnost nisu potpuno razjašnjeni.
English: Olaparib does not affect the pharmacokinetics of tamoxifen.
Croatian: Olaparib ne utječe na farmakokinetiku tamoksifena.
English: If you take more Lynparza than your normal dose, contact your doctor or the nearest hospital straight away.
Croatian: Ako uzmete veću dozu lijeka Lynparza od uobičajene, odmah se obratite svom liječniku ili otiđite u najbližu bolnicu.
English: Sixty-three percent (63%) of the patients had upfront debulking surgery and of these the majority (75%) had no macroscopic residual disease.
Croatian: Šezdeset i tri posto (63%) bolesnica prethodno je bilo podvrgnuto kirurškom zahvatu radi smanjenja tumorske mase te većina njih (75%) nije imala makroskopski vidljivu rezidualnu bolest.
English: The gBRCAm status of patients enrolled via local testing was confirmed retrospectively by central testing.
Croatian: Pozitivan status gBRCA mutacija kod bolesnica koje su u ispitivanje uključene na temelju lokalnog testiranja retrospektivno je potvrđen centralnim testiranjem.
English: Female partners of male patients must also use highly effective contraception if they are of childbearing potential (see section 4.4).
Croatian: Partnerice bolesnika muškog spola također moraju koristiti visokoučinkovitu kontracepciju ako su reproduktivne dobi (vidjeti dio 4.4).