Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Reduction of tied up capital through changed inventory control : A study at Husqvarna Group focusing on purchases from remote suppliers

Studien utfördes under våren -18 som ett examensarbete på Husqvarna Group gentemot företagets inköpsavdelning. Författarna studerar masterutbildningen Logistik som en del av sin civilingenjörsutbildning på Linköpings Universitet.  Studiens huvudämnen är inköp och lagerstyrning, med fokus på den senare delen och ämnade att minska kapitalbindning utan att öka de totala kostnaderna genom en förändring. Säkerhetslager, orderkvantiteter och konsignationslager var de tre centrala områdena som undersöktes och fyra olika scenarion skapades inom dessa. Utöver kostnad och kapitalbindning utvärderades de även efter hur de påverkade flexibiliteten för Husqvarna. De två scenariona som utreddes inom säkerhetslager var servicenivåmetoden Scenario 1 - SERV1 och användningen av Scenario 2 - Procentandel av efterfrågan under ledtiden. Inom orderkvantiteter undersöktes ett scenario baserat på ekonomisk orderkvantitet, Scenario 3 – EOK. Kvalitativt utreddes också ett konsignationslagerupplägg genom Scenario 4 – Konsignationslager.  Intervjuer och information från företagets affärssystem har varit de centrala informationskällorna till studien, där säkerhetslager- och orderkvantitetsförändringarna utvärderades kvantitativt och konsignationslager kvalitativt. Studien har fokuserat på två avlägsna leverantörer belägna i Asien.  Studiens resultat blev att användning av servicenivåmetoden SERV1 för dimensionering av säkerhetslager minskar företagets kapitalbindning med 13,6 % och de totala kostnaderna med 15,9 %, med den ytterligare effekten av en högre samt jämnare servicenivå för hela produktsortimentet. Även dimensioneringen av orderkvantiteter genom ekonomisk orderkvantitet gav minskad kapitalbindning med 9,8 % och en marginell minskning av de totala kostnaderna. De procentuella förändringarna är i förhållande till nuläget och de kostnadsposter som förändras i samband med scenariots införande. Ett konsignationslagerupplägg kommer minska kapitalbindningen, men kostnaderna skulle troligen öka vid omställningen från nuläget. Vid detta val är det viktigt att utvärdera vinsten av att frigöra kapital gentemot att öka kostnaderna. Scenario 2 – Procentandel av efterfrågan under ledtiden inom säkerhetslager ansågs inte ge ett tillräckligt bra resultat för att det skulle vara värt att gå vidare med för Husqvarna.  Slutsatsen av studien är att Husqvarna Group bör dimensionera om sina säkerhetslager och se över sina orderkvantiteter för de befintliga artiklarna enligt de rekommenderade metoderna. De bör även vid uppstart av nya artiklar öka fokus på bestämmandet av orderkvantiteten. Konsignationslager bör utredas vidare utifrån svårigheter med det samt för att kvantitativt utreda kostnader. Resultatet av studien kan användas för både avlägsna samt närliggande leverantörer, och anses därför vara generaliserbart för alla Husqvarnas produkter och för andra företag.The study was conducted during the spring -18 as a graduate work at Husqvarna Group towards the company's purchasing department. The authors study the master’s program Logistics as part of their MSc in Engineering at Linköping University.  The main subjects of the study are purchasing and inventory management, focusing on the latter part and intended to reduce capital tied up without increasing overall costs through a change. Security stock, order quantities and consignment storage were the three key areas investigated and four different scenarios were created within these. In addition to cost and tied up capital, the scenarios were also evaluated according to how they affected the flexibility of Husqvarna. The two scenarios investigated in security stock were the service level method Scenario 1 - SERV1 and Scenario 2 - Percentage of demand during lead time. Within order quantities, a scenario based on economic order quantity, Scenario 3 - EOK, was investigated. Qualitatively, a consignment inventory was also investigated through Scenario 4 - Consignment storage.  Interviews and information from the company's business systems have been the key sources of information for the study, where the safety stock and order quantity changes were quantitatively evaluated and consignment storage qualitatively. The study has focused on two remote suppliers located in Asia.  The study found that using the SERV1 service-level methodology reduces the company's tied up capital by 13.6% and total costs by 15.9%, with the additional effect of a higher and more even service level for the entire product range. Also, deciding the order quantities by using economic order quantity resulted in a reduction of 9,8% in capital tied up and a marginal decrease in total costs. The percentage changes are in relation to the current situation and the costs which change in connection with the introduction of the scenarios are included. A consignment storage will reduce capital tied up, but the costs would probably increase in the transition from the present. In this scenario, it is important to evaluate the profit of decreasing tied up capital to the increased costs. Scenario 2 - Percentage of demand during the lead time was not considered to give a sufficiently good result and is for that reason not worth for Husqvarna to move forward with.  The conclusion of the study is that Husqvarna Group should dimension its security stocks and review its order quantities for the existing articles according to the recommended methods. They should also focus on determining the order quantity when starting to buy new articles. Consignment storage should be further investigated on the basis of difficulties to quantitatively investigate costs. The result of the study can be used for both remote and nearby suppliers and is therefore considered to be generalizable for all Husqvarna products and also for other companies

Reduction of tied up capital through changed inventory control : A study at Husqvarna Group focusing on purchases from remote suppliers

Studien utfördes under våren -18 som ett examensarbete på Husqvarna Group gentemot företagets inköpsavdelning. Författarna studerar masterutbildningen Logistik som en del av sin civilingenjörsutbildning på Linköpings Universitet.  Studiens huvudämnen är inköp och lagerstyrning, med fokus på den senare delen och ämnade att minska kapitalbindning utan att öka de totala kostnaderna genom en förändring. Säkerhetslager, orderkvantiteter och konsignationslager var de tre centrala områdena som undersöktes och fyra olika scenarion skapades inom dessa. Utöver kostnad och kapitalbindning utvärderades de även efter hur de påverkade flexibiliteten för Husqvarna. De två scenariona som utreddes inom säkerhetslager var servicenivåmetoden Scenario 1 - SERV1 och användningen av Scenario 2 - Procentandel av efterfrågan under ledtiden. Inom orderkvantiteter undersöktes ett scenario baserat på ekonomisk orderkvantitet, Scenario 3 – EOK. Kvalitativt utreddes också ett konsignationslagerupplägg genom Scenario 4 – Konsignationslager.  Intervjuer och information från företagets affärssystem har varit de centrala informationskällorna till studien, där säkerhetslager- och orderkvantitetsförändringarna utvärderades kvantitativt och konsignationslager kvalitativt. Studien har fokuserat på två avlägsna leverantörer belägna i Asien.  Studiens resultat blev att användning av servicenivåmetoden SERV1 för dimensionering av säkerhetslager minskar företagets kapitalbindning med 13,6 % och de totala kostnaderna med 15,9 %, med den ytterligare effekten av en högre samt jämnare servicenivå för hela produktsortimentet. Även dimensioneringen av orderkvantiteter genom ekonomisk orderkvantitet gav minskad kapitalbindning med 9,8 % och en marginell minskning av de totala kostnaderna. De procentuella förändringarna är i förhållande till nuläget och de kostnadsposter som förändras i samband med scenariots införande. Ett konsignationslagerupplägg kommer minska kapitalbindningen, men kostnaderna skulle troligen öka vid omställningen från nuläget. Vid detta val är det viktigt att utvärdera vinsten av att frigöra kapital gentemot att öka kostnaderna. Scenario 2 – Procentandel av efterfrågan under ledtiden inom säkerhetslager ansågs inte ge ett tillräckligt bra resultat för att det skulle vara värt att gå vidare med för Husqvarna.  Slutsatsen av studien är att Husqvarna Group bör dimensionera om sina säkerhetslager och se över sina orderkvantiteter för de befintliga artiklarna enligt de rekommenderade metoderna. De bör även vid uppstart av nya artiklar öka fokus på bestämmandet av orderkvantiteten. Konsignationslager bör utredas vidare utifrån svårigheter med det samt för att kvantitativt utreda kostnader. Resultatet av studien kan användas för både avlägsna samt närliggande leverantörer, och anses därför vara generaliserbart för alla Husqvarnas produkter och för andra företag.The study was conducted during the spring -18 as a graduate work at Husqvarna Group towards the company's purchasing department. The authors study the master’s program Logistics as part of their MSc in Engineering at Linköping University.  The main subjects of the study are purchasing and inventory management, focusing on the latter part and intended to reduce capital tied up without increasing overall costs through a change. Security stock, order quantities and consignment storage were the three key areas investigated and four different scenarios were created within these. In addition to cost and tied up capital, the scenarios were also evaluated according to how they affected the flexibility of Husqvarna. The two scenarios investigated in security stock were the service level method Scenario 1 - SERV1 and Scenario 2 - Percentage of demand during lead time. Within order quantities, a scenario based on economic order quantity, Scenario 3 - EOK, was investigated. Qualitatively, a consignment inventory was also investigated through Scenario 4 - Consignment storage.  Interviews and information from the company's business systems have been the key sources of information for the study, where the safety stock and order quantity changes were quantitatively evaluated and consignment storage qualitatively. The study has focused on two remote suppliers located in Asia.  The study found that using the SERV1 service-level methodology reduces the company's tied up capital by 13.6% and total costs by 15.9%, with the additional effect of a higher and more even service level for the entire product range. Also, deciding the order quantities by using economic order quantity resulted in a reduction of 9,8% in capital tied up and a marginal decrease in total costs. The percentage changes are in relation to the current situation and the costs which change in connection with the introduction of the scenarios are included. A consignment storage will reduce capital tied up, but the costs would probably increase in the transition from the present. In this scenario, it is important to evaluate the profit of decreasing tied up capital to the increased costs. Scenario 2 - Percentage of demand during the lead time was not considered to give a sufficiently good result and is for that reason not worth for Husqvarna to move forward with.  The conclusion of the study is that Husqvarna Group should dimension its security stocks and review its order quantities for the existing articles according to the recommended methods. They should also focus on determining the order quantity when starting to buy new articles. Consignment storage should be further investigated on the basis of difficulties to quantitatively investigate costs. The result of the study can be used for both remote and nearby suppliers and is therefore considered to be generalizable for all Husqvarna products and also for other companies

Implementing a useable e-shop for textile patches : A practical case study of the web application Festing

This report covers the development of the web application Festing and the results and experiences which have been reached and learned during the process. The purpose of the study was to examine how the selling of patches could be both simplified and improved by using an advanced web application designed with focus on usability. Currently the patches are sold in a large but geographically and temporally limited market at Linköping University. The project was comprised of a case study and development of an application following the agile project framework Scrum. According to this the projects has been split up into four sprints after each of which a working product was delivered. This resulted in a usable web application with an intuitive design and multiple functions linked to the selling and buying of patches. Based on interviews, surveys and usability tests this web application is considered to have the long-term potential to take over the current physical market of textile patches.Rapporten omfattar beskrivningen av utvecklingsprocessen för webbapplikationen Festing samt resultat och erfarenheter som uppnåtts och anskaffats under processens gång. Syftet med studien var att utveckla en avancerad webbapplikation av typ e-butik för att undersöka hur försäljningen av tygmärken kan förenklas och förbättras av en webbapplikation med fokus på användbarhet. Detta då försäljningen i dagsläget består av en stor men fysiskt och geografiskt begränsad marknad vid Linköpings universitet. Projektet har utformats som en fallstudie och utveckling av en webbapplikation enligt det agila arbetssättet Scrum. Arbetet har delats upp i fyra stycken olika sprintar där det i slutet av varje sprint ska ha levererats en fungerande delprodukt. Detta resulterade i en användbar webbapplikation med intuitiv design och flertalet funktioner kopplade till försäljning och köp av tygmärken. Utifrån intervjuer, enkätundersökningar och användbarhetstester anses denna webbapplikation ha potential till att på lång sikt kunna ta över den nuvarande fysiska försäljningen av tygmärken

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs

Polygenic risk scores for prediction of breast cancer and breast cancer subtypes

Abstract Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs