natgillin/translations-raw huggingface dataset:
Verzenios er et kræftlægemiddel til behandling af kvinder med brystkræft, der er fremskreden eller har spredt sig til andre dele af kroppen.
Verzenios is a cancer medicine used to treat women with breast cancer that is advanced or has spread to other parts of the body.
Det aktive stof i Verzenios, abemaciclib, blokerer aktiviteten af en række enzymer, der kaldes cyklinafhængige kinaser (CDK4 og CDK6), og som spiller en vigtig rolle i reguleringen af den måde, som celler vokser og deler sig på.
The active substance in Verzenios, abemaciclib, blocks the activity of enzymes known as cyclindependent kinases (CDK) 4 and 6, which play a key role in regulating the way cells grow and divide.
Hvad er Verzenios, og hvad anvendes det til?
What is Verzenios and what is it used for?
Verzenios kan kun anvendes, når kræftcellerne har en bestemt type receptorer (hormonreceptorer) på deres overflade (HR-positiv brystkræft) og ikke producerer unormalt store mængder af de såkaldte HER2-receptorer (HER2-negativ brystkræft).
Verzenios can only be used when the cancer cells have certain types of receptor (called hormone receptors) on their surface (HR-positive) and do not produce abnormally large quantities of another receptor called HER2 (HER2-negative).
Hvorfor blev Verzenios godkendt i EU?
Why is Verzenios authorised in the EU?
Grapefrugtjuice bør undgås under behandling med Verzenios, da grapefrugtjuice kan påvirke lægemidlets optagelse og nedbrydning i kroppen.
Grapefruit juice should be avoided during treatment with Verzenios as it may affect the way the medicine is absorbed and broken down in the body.
Verzenios anvendes sammen med et hormonpræparat, enten en aromatase-hæmmer eller fulvestrant.
It is used together with a hormonal medicine, either an aromatase inhibitor or fulvestrant.
Hvilke risici er der forbundet med Verzenios?
What are the risks associated with Verzenios?
Den fuldstændige liste over bivirkninger og begrænsninger ved Verzenios fremgår af indlægssedlen.
For the full list of side effects and restrictions of Verzenios, see the package leaflet.
To hovedstudier med 1.162 kvinder (primært kvinder efter overgangsalderen), der havde HR-positiv, HER2-negativ brystkræft, som var begyndt at sprede sig, viste, at Verzenios kan forlænge den tid, patienterne overlever, uden at sygdommen forværres (progressionsfri overlevelse).
Two main studies, involving 1,162 women, mostly postmenopausal, with HR-positive, HER2-negative breast cancer that had started to spread, showed that Verzenios can prolong the time patients live without their disease getting worse (progression-free survival).
Blokeringen af CDK4 og CDK6 bremser væksten af HR-positive brystkræftceller.
By blocking CDK4 and CDK6, Verzenios slows the growth of HR-positive breast cancer cells.
I et tredje studie, der omfattede 132 kvinder, som havde fået tidligere kræftbehandling, blev der ikke påvist gavnlig effekt ved anvendelse af Verzenios alene til behandling af HR-positiv, HER2-negativ brystkræft, der var begyndt at sprede sig.
A third study, conducted in 132 women who had received previous cancer treatment, failed to demonstrate that Verzenios used on its own was of benefit in the treatment of HR-positive, HER2negative breast cancer that had started to spread.
Verzenios anvendt sammen med en aromatase-hæmmer eller fulvestrant øgede den tid, der gik, inden sygdommen forværredes hos kvinder efter overgangsalderen med HR-positiv og HER2-negativ brystkræft, der var fremskreden eller havde spredt sig.
Verzenios used with an aromatase inhibitor or fulvestrant increased the time it took for the disease to get worse in postmenopausal women with HR-positive and HER2-negative breast cancer that is advanced or metastatic.
Hvordan anvendes Verzenios?
How is Verzenios used?
Hvordan virker Verzenios?
How does Verzenios work?
Der er anført anbefalinger og forholdsregler i produktresuméet og indlægssedlen, som patienter og sundhedspersonale skal følge for at sikre risikofri og effektiv anvendelse af Verzenios.
Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Verzenios have been included in the summary of product characteristics and the package leaflet.
Hvilke fordele viser studierne, at der er ved Verzenios?
What benefits of Verzenios have been shown in studies?
I det andet studie overlevede de kvinder, der fik Verzenios og fulvestrant, gennemsnitligt i 16 måneder uden sygdomsforværring, mens de kvinder, der fik placebo og fulvestrant, overlevede i 9 måneder uden sygdomsforværring.
In the second study women taking Verzenios and fulvestrant lived on average 16 months without their disease getting worse, compared with 9 months for women taking placebo and fulvestrant.
I det første studie overlevede de kvinder, der fik Verzenios og en aromatase-hæmmer (letrozol eller anastrozol), gennemsnitligt i 28 måneder uden sygdomsforværring, mens de kvinder, der fik placebo (ikke-aktivt stof) og en aromatase-hæmmer, overlevede i 15 måneder uden sygdomsforværring.
In the first study women taking Verzenios and an aromatase inhibitor (letrozole or anastrozole) lived on average 28 months without their disease getting worse compared with 15 months for women taking placebo (a dummy treatment) and an aromatase inhibitor.
CDK4 og CDK6 øget, og det hjælper kræftcellerne med at dele sig ukontrolleret.
In some cancers, including HR-positive breast cancer, the activity of CDK 4 and 6 is increased, which helps the cancer cells to multiply uncontrollably.
Denne tilladelse var baseret på tilladelsen for Prepandrix i 2008 (”informeret samtykke”).
This authorisation was based on the authorisation granted to Prepandrix in 2008 (‘informed consent').
Andre oplysninger om vaccinen:
Other information about the vaccine:
Den fuldstændige EPAR for vaccinen findes her.
The full EPAR for the vaccine can be found here.
Virussen er først blevet inaktiveret, så den ikke er sygdomsfremkaldende.
The virus has first been inactivated so that it does not cause any disease.
Udvalget anbefalede udstedelse af markedsføringstilladelse for vaccinen.
The Committee recommended that the vaccine be given marketing authorisation.
Dette medvirker til at beskytte mod den sygdom, virussen forårsager.
This may help to protect against the disease caused by the virus.
Det var nødvendigt at give disse patienter dobbeltdoser af vaccinen for at opnå beskyttelse.
These patients needed double doses of the vaccine for protection.
Injektionerne blev givet med 21 dages mellemrum.
The injections were given 21 days apart.
En influenzapandemi forekommer, når der opstår en ny stamme af en influenzavirus, der let spredes fra en person til en anden, fordi mennesker ikke har nogen immunitet (beskyttelse) over for den. En pandemi kan berøre de fleste lande og regioner i verden.
A flu pandemic happens when a new strain of flu virus appears that can spread easily from person to person because people have no immunity (protection) against it. A pandemic can affect most countries and regions around the world.
Vaccination bør udskydes hos personer, der pludselig har fået feber.
Vaccination should be delayed in people who have a sudden fever.
Vacciner virker ved at ‘lære' immunsystemet (kroppens naturlige forsvar), hvordan det skal forsvare kroppen mod en sygdom.
Vaccines work by ‘teaching' the immune system (the body's natural defences) how to defend itself against a disease.
Emulsionen indeholder et "adjuvans" (en olieholdig forbindelse), som giver en bedre respons.
The emulsion contains an ‘adjuvant' (a compound containing oil) to stimulate a better response.
Vaccinen er blevet udviklet for at yde beskyttelse mod denne stamme, så den kan anvendes før eller under en influenzapandemi.
The vaccine has been developed to provide protection against this strain, so that it can be used before or during a flu pandemic.
Ifølge de kriterier, der er fastlagt af Udvalget for Humanmedicinske Lægemidler (CHMP), skal en præpandemisk vaccine kunne frembringe en beskyttende mængde antistoffer hos mindst 70 % af de vaccinerede, for at den anses for egnet.
According to criteria laid down by the Committee for Medicinal Products for Human Use (CHMP), a prepandemic vaccine needs to bring about protective levels of antibodies in at least 70% of people for it to be considered suitable.
Hos de ældre personer opfyldte vaccinen givet i enkeltdoser også disse kriterier, undtagen hos et fåtal af patienterne, som var over 80 år og ikke var beskyttet mod virussen ved undersøgelsens start.
In elderly people, single doses of this vaccine also met these criteria, except for in the small number of patients aged over 80 years who did not have any protection against the virus at the start of the study.
Denne blandede “emulsion” kan derefter injiceres.
The resulting ‘emulsion' is then injected.
Inden brug skal vaccinen gøres klar ved at blande en suspension, der indeholder viruspartiklerne, med en emulsion.
Before use, the vaccine is made up by mixing together a suspension that contains the virus particles with an emulsion.
21 dage efter den anden injektion havde 84 % af de vaccinerede opnået et antistofniveau, som kunne beskytte dem mod H5N1.
At 21 days after the second injection, 84% of the people receiving the vaccine had levels of antibodies that would protect them against H5N1.
Det er en særlig form for vaccine, som skal beskytte mod en influenzavirusstamme, der kan forårsage en fremtidig pandemi.
This is a special type of vaccine that is intended to protect against a strain of flu that may cause a future pandemic.
Hvilken risiko er der forbundet med vaccinen?
What is the risk associated with the vaccine?
Vaccinen indeholder en influenzavirusstamme kaldet ”A/VietNam/1194/2004 NIBRG-14” (H5N1).
The vaccine contains a flu strain called ‘A/VietNam/1194/2004 NIBRG-14' (H5N1).
Sundhedseksperterne er bekymrede for, at der i fremtiden kan opstå en influenzapandemi forårsaget af H5N1-stammen af virussen.
Health experts are concerned that a future flu pandemic could be caused by the H5N1 strain of the virus.
Deltagerne fik to injektioner af vaccinen, som indeholdt en af fire forskellige doser af hæmagglutinin.
The participants received two injections of the vaccine containing one of four different doses of haemagglutinin.
Den fuldstændige liste over alle de indberettede bivirkninger ved vaccinen fremgår af indlægssedlen.
For the full list of all side effects reported with the vaccine, see the Package Leaflet.
Vaccinen gives ved injektion i skuldermusklen i to enkeltdoser med mindst tre ugers mellemrum.
The vaccine is given by injection into the shoulder muscle in two single doses, at least three weeks apart.
Behandlingens virkning blev hovedsagelig bedømt på mængden af antistoffer mod influenzavirussen i blodet på tre forskellige tidspunkter: inden vaccinationen, den dag, den anden vaccination blev givet (dag 21), og 21 dage senere (dag 42).
The main measures of effectiveness were the levels of antibodies against the flu virus in the blood at three different times: before vaccination, on the day of the second injection (day 21) and 21 days later (day
Hovedundersøgelsen viste, at vaccinen indeholdt 3,75 mikrogram hæmagglutinin, og at adjuvanset udløste en antistofrespons, der opfyldte disse kriterier.
The main study showed that the vaccine containing 3.75 micrograms of haemagglutinin and the adjuvant produced an antibody response that met these criteria.
Vaccinen må ikke gives til personer, der har haft en anafylaktisk reaktion (svær overfølsomhedsreaktion) over for en af vaccinens komponenter eller andre af de stoffer, vaccinen indeholder meget små mængder af, f.eks. æg, kyllingeprotein, ovalbumin (et protein i æggehvide), formaldehyd, gentamicinsulfat (et antibiotikum) og natriumdeoxycholat.
The vaccine should not be given to people who have had an anaphylactic reaction (severe allergic reaction) to any of the components of the vaccine, or to any of the substances found at very low levels in the vaccine, such as eggs, chicken protein, ovalbumin (a protein in egg white), formaldehyde, gentamicin sulphate (an antibiotic) and sodium deoxycholate.
Hvorfor blev vaccinen godkendt?
Why has the vaccine been approved?
Det kan være nødvendigt at give personer over 80 år en dobbeltdosis af vaccinen (en injektion i hver skulder), hvilket gentages tre uger senere.
Adults over 80 years of age may need a double dose of the vaccine (one injection into each shoulder) with a second double dose three weeks later.
En anden undersøgelse hos 437 personer over 60 år så på immunogeniciteten ved enkelt- og dobbeltdoser af vaccinen.
A further study looked at the immunogenicity of single or double doses of the vaccine in 437 people aged over 60 years.
Hvilken fordel viser undersøgelserne, at der er ved vaccinen?
What benefit has the vaccine shown during the studies?
Europa-Kommissionen udstedte en markedsføringstilladelse med gyldighed i hele Den Europæiske Union for Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals til GlaxoSmithKline Biologicals S.A. den 26. september 2008.
The European Commission granted a marketing authorisation valid throughout the EU for Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals to GlaxoSmithKline Biologicals S.A. on 26 September 2008.
Hvad anvendes vaccinen til?
What is the vaccine used for?
Når en person vaccineres, opfatter immunsystemet virussen som "fremmed" og danner antistoffer mod den. Immunsystemet kan således danne antistoffer hurtigere, når det eksponeres for samme virus igen.
When a person is given the vaccine, the immune system recognises the virus as ‘foreign' and makes antibodies against it.
De mest almindelige bivirkninger ved Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals (som ses ved mere end 1 ud af 10 doser af vaccinen) er hovedpine, ledsmerter, muskelsmerter, reaktioner på injektionsstedet (hårdhed, hævelse, smerte og rødme), feber og træthed.
The most common side effects with Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals (seen with more than 1 in 10 doses of the vaccine) are headache, arthralgia (joint pain), myalgia (muscle pain), reactions at the site of the injection (hardening, swelling, pain and redness), fever and fatigue (tiredness).
Denne vaccine indeholder små mængder hæmagglutinin (overfladeproteiner)
This vaccine contains small amounts of haemagglutinins (proteins from the surface) of the H5N1 virus.
Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals præpandemisk influenzavaccine (H5N1) (split virion, inaktiveret, adjuveret) (A/VietNam/1194/2004 NIBRG-14)
Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals prepandemic influenza vaccine (H5N1) (split virion, inactivated, adjuvanted) (A/VietNam/1194/2004 NIBRG-14)
Hvordan blev vaccinen undersøgt?
How has the vaccine been studied?
Den sammenlignede vaccinens evne til i forskellige doser med eller uden adjuvans at fremme dannelsen af antistoffer (”immunogeniciteten”).
The main study of the vaccine included 400 healthy adults aged between 18 and 60 years and compared the ability of different doses of the vaccine, with or without the adjuvant, to trigger the production of antibodies (‘immunogenicity').
CHMP fandt, at fordelene ved Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals er større end risiciene til aktiv immunisering mod H5N1undertypen af influenza A-virus.
The CHMP decided that the benefits of Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals are greater than its risks for active immunisation against H5N1 subtype of influenza A virus.
Hvordan virker vaccinen?
How does the vaccine work?
Hvad er Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals?
What is Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals?
Hvordan anvendes vaccinen?
How is the vaccine used?
Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals er en vaccine, som gives ved injektion.
Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals is a vaccine that is given by injection.
Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals er en ‘præpandemisk' vaccine.
Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals is a ‘prepandemic' vaccine.
Præpandemisk Influenzavaccine (H5N1) (Split Virion, Inaktiveret, Adjuveret) GlaxoSmithKline Biologicals er en vaccine til voksne til beskyttelse mod influenza forårsaget af H5N1-stammen af influenzavirus A. Vaccinen gives i overensstemmelse med de officielle anbefalinger.
Prepandemic Influenza Vaccine (H5N1) (Split Virion, Inactivated, Adjuvanted) GlaxoSmithKline Biologicals is a vaccine for use in adults to protect against flu caused by the H5N1 strain of the influenza A virus.
Meget sjælden, ikke kendt*
Very rare, not known
* Information relateret til clopidogrel med hyppighed ”ikke kendt”.
* Information related to clopidogrel with frequency “not known”.
• hvis du lider af alvorlig leversygdom.
If you suffer from severe liver disease.
Visse andre lægemidler kan påvirke brugen af Clopidogrel Acino eller omvendt.
Some other medicines may influence the use of Clopidogrel Acino or vice versa.
Dato for første markedsføringstilladelse: 28. juli 2009 Dato for seneste fornyelse: 21. marts 2014
Date of latest renewal: 21 march 2014
Hyppighed defineres i henhold til følgende konvention: almindelig (>1/100 til <1/10), ikke almindelig (>1/1.000 til <1/100), sjælden (>1/10.000 til <1/10.000), meget sjælden <1/10.000), ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Their frequency is defined using the following conventions: common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).
I øvrigt kan din læge eventuelt finde ændringer i resultaterne af din blod- eller urinprøver.
In addition, your doctor may identify changes in your blood or urine test results.
• hvis du er allergisk over for clopidogrel eller et af de øvrige indholdsstoffer i dette lægemiddel (se afsnit 6).
• If you are allergic to clopidogrel or any of the other ingredients of this medicine (listed in section 6).
Brug af Clopidogrel Acino sammen med mad og drikke Clopidogrel Acino kan tages med eller uden mad.
Clopidogrel Acino with food and drink Clopidogrel Acino may be taken with or without food.
14 filmovertrukne tabletter 28 filmovertrukne tabletter 30 filmovertrukne tabletter 50 filmovertrukne tabletter 84 filmovertrukne tabletter 90 filmovertrukne tabletter 100 filmovertrukne tabletter
14 film-coated tablets 28 film-coated tablets 30 film-coated tablets 50 film-coated tablets 84 film-coated tablets 90 film-coated tablets 100 film-coated tablets
Det indeholder også hydrogeneret ricinusolie.
It also contains hydrogenated castor oil.
Din læge bør have udskrevet Clopidogrel Acino plus acetylsalicylsyre, hvis du ikke må tage ”orale antikoagulantia”, og du ikke har risiko for alvorlig blødning.
Your doctor should have prescribed Clopidogrel Acino plus acetylsalicylic acid if you cannot take ‘oral anticoagulants' and you do not have a risk of major bleeding.
Blodplader (såkaldte trombocytter) er meget små bestanddele, som klumper sig sammen, i forbindelse med, at blodet størkner.
Platelets (so-called thrombocytes) are very small structures, which clump together during blood clotting.
Forekomsten af svære tilfælde var ens for clopidogrel og for ASA.
The incidence of severe cases was similar for clopidogrel and ASA.
Populationen inkluderede 27,8 % kvinder, 58,4 % patienter ≥60 år (26 % ≥70 år) og 54,5 % patienter der fik fibrinolytika.
The population included 27.8% women, 58.4% patients ≥ 60 years (26% ≥ 70 years) and 54.5% patients who received fibrinolytics.
Du skal fortsætte med at tage Clopidogrel Acino, så længe din læge udskriver det til dig.
You should take Clopidogrel Acino for as long as your doctor continues to prescribe it.
Navn og adresse den fremstiller, der er ansvarlig for batchfrigivelse
Name and address of the manufacturer responsible for batch release
Ud over ovenstående oplysninger om specifik lægemiddelinteraktion er der ikke udført interaktionsstudier med clopidogrel og visse lægemidler, som almindeligvis gives til patienter med aterotrombotiske sygdomme.
Apart from the specific medicinal products interaction information described above, interaction studies with clopidogrel and some medicinal products commonly administered in patients with atherothrombotic disease have not been performed.
NAVN PÅ INDEHAVEREN AF MARKEDSFØRINGSTILLADELSEN Acino AG
NAME OF THE MARKETING AUTHORISATION HOLDER Acino AG
Glomerulonefrit, forhøjetblodkreatinin
Glomerulonephritis, blood creatinine increased
Hvis du skærer dig eller kommer til skade, kan det tage lidt længere end normalt, før blødningen stopper.
If you cut or injure yourself, it may take longer than usual for bleeding to stop.
Andre alleler, der associeres med manglende eller nedsat metabolisme er mindre hyppige og inkluderer CYP2C19*4, *5, *6, *7 og *8..
Other alleles associated with absent or reduced metabolism are less frequent and include CYP2C19*4, *5, *6, *7, and *8.
Hvis du glemmer at tage en dosis Clopidogrel Acino til sædvanlig tid, men kommer i tanke om det i løbet af 12 timer, skal du omgående tage tabletten og dernæst tage den næste tablet til sædvanlig tid.
If you forget to take a dose of Clopidogrel Acino, but remember within 12 hours of your usual time, take your tablet straight away and then take your next tablet at the usual time.
DATO FOR ÆNDRING AF TEKSTEN <MM/ÅÅÅÅ>
DATE OF REVISION OF THE TEXT <{MM/YYYY}>
Yderligere oplysninger om dette lægemiddel findes på Det Europæiske Lægemiddelagenturs hjemmeside http://www.ema.europa.eu/.
Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.
Hvis du har taget for mange Clopidogrel Acino Kontakt din læge eller tag på den nærmeste skadestue på grund af den øgede blødningsrisiko.
If you take more Clopidogrel Acino than you should Contact your doctor or the nearest hospital emergency department because of the increased risk of bleeding.
Du bør være blevet informeret om, at ”orale antikoagulantia” er mere effektive mod denne sygdom end acetylsalicylsyre eller kombinationen af Clopidogrel Acino og acetylsalicylsyre.
You should have been told that ‘oral anticoagulants' are more effective than acetylsalicylic acid or the combined use of Clopidogrel and acetylsalicylic acid for this condition.
Brug ikke lægemidlet, hvis du bemærker synlige tegn på skade på blisterpakningen eller de filmovertrukne tabletter.
Do not use Clopidogrel Acino if you notice any visible sign of damage of blister or film-coated tablets.
CYP2C19*1allelen svarer til en fuldt funktionel metabolisme, mens CYP2C19*2 og CYP2C19*3 allelerneikke er funktionelle.
The CYP2C19*1 allele corresponds to fully functional metabolism while the CYP2C19*2 and CYP2C19*3 alleles are nonfunctional.
Hvis du ammer eller planlægger at amme,skal du tale med din læge, før du tager denne medicin.
If you are breastfeeding or planning to breast-feed, talk to your doctor before taking this medicine.
Data fra CAPRIE-studiet indikerer, at phenytoin og tolbutamid, som metaboliseres af CYP2C9, kan administreres samtidig med clopidogrel uden risiko.
Data from the CAPRIE study indicate that phenytoin and tolbutamide which are metabolised by CYP2C9 can be safely co-administered with clopidogrel.
Hvis du får langvarige blødninger, mens du tager Clopidogrel Acino.
If you experience prolonged bleeding when taking Clopidogrel Acino.
Trafik- og arbejdssikkerhed Det er usandsynligt, at Clopidogrel Acino vil påvirke din evne til at køre eller betjene maskiner.
Driving and using machines Clopidogrel Acino is unlikely to affect your ability to drive or to use machines.