Modern perception of images created in Walt Whitman’s „Song of myself“, section 6

https://www.ester.ee/record=b5238364*es

Large Scale Data Analysis Using Apache Pig

Käesolev magistritöö kirjeldab andmete paralleeltöötluseks mõeldud tarkvararaamistiku Apache Pig kasutamist. Esitatud on konkreetne andmeanalüüsi ülesanne, mille lahendamiseks raamistikku kasutati. Selle töö eesmärk on näidata Pig-i kasulikkust suuremahuliseks andmeanalüüsiks. Raamistik Pig on loodud töötama koos paralleelarvutuste tegemise infrastruktuuriga Hadoop. Hadoop realiseerib MapReduce programmeerimismudelit. Pig käitub lisa-abstraktsioonitasemena MapReduce-i kohal, esitades andmeid relatsiooniliste tabelitena ning lubades programmeerijatel teha päringuid, kasutades Pig Latin päringukeelt. Pig-i testimiseks püstitati andmeanalüüsi ülesanne, mis oli vaja lahendada. Üheks osaks ülesandest oli RSS veebivoogudest kogutud uudistest päevade kaupa levinumate sõnade tuvastamine. Teine osa oli, suvalise sõnade hulga puhul, kogutud uudistest leidmine, kuidas muutus päevade kaupa selle sõnade hulga koosesinemiste arv uudistes. Lisaks tuli Pig-i kasutades realiseerida regulaaravaldisi rakendav teksti otsing kogutud uudiste seast. Probleemi lahendusena realiseeriti hulk Pig Latin keelseid skripte, mis töötlevad ja analüüsivad kogutud andmeid. Funktsionaalsuse kokku sidumiseks loodi programmeerimiskeeles Java raamprogramm, mis käivitab erinevaid Pig skripte vastavalt kasutaja sisendile. Andmete kogumiseks loodi eraldi rakendus, mida kasutati regulaarsete intervallide järel uudisvoogude failide alla laadimiseks. Loodud rakendust kasutati kogutud andmete analüüsiks ja töös on esitatud ka mõned analüüsi tulemused. Tulemustest võib näha, kuidas teatud sõnade ja sõnakombinatsioonide esinemissagedused muutuvad seoses sellega, kuidas sündmuste, mida need sõnad kirjeldavad, aktuaalsus suureneb ja väheneb.This work describes Apache Pig, a software framework designed for parallel data processing. An example data analysis problem is presented and solved using the framework. The objective of the work is to demonstrate the usefulness of Pig for large scale data analysis. Pig is built to work with the parallel computing framework Hadoop, which implements the MapReduce programming model. Pig acts as a layer of abstraction on top of MapReduce, presenting data as relational tables and allowing for data manipulation and queries in the Pig Latin query language. The data analysis problem used to test Pig involved collecting news stories from on-line RSS web feeds and identifying trends in the topics covered. As the solution, a number of Pig scripts were created to perform the necessary tasks and a Java application was implemented as a user interface wrapper for the Pig scripts

Comparsion and analysis of Tallinn and Tartu cycling strategies on the example of Helsinki and Copenhagen cycling strategies

Bakalaureusetöö Keskkonnakaitse õppekavalEesti linnades, Tallinnas ja Tartus, toimub autostumise kasv, kuid linnaliikuvuse parendamiseks tuleb edendada jalgrattaliiklust, mille paremaks elluviimiseks on Tartul ja Tallinnal valminud jalgrattastrateegiad. Käesoleva bakalaureusetöö eesmärgiks on analüüsida Tartu ja Tallinna jalgrattastrateegiaid ning võrrelda neid mõõdikute alusel Kopenhaageni ja Helsingi jalgrattastrateegiatega. Mõõdikuteks valiti ohutus, mugavus, sidusus, otseühendus (ühenduskiirus) ja atraktiivsus. Töö käigus leiti, et kuna käsitletud linnade jalgrattastrateegiate eesmärgid ja seetõttu ka tegevused on mõnevõrra erinevad (tulenedes eelkõige linnade rattaliikluse olemasolevast olukorrast), oli neid keerulisem võrrelda, kui algselt arvati. Siiski oli võimalik valitud mõõdikute alusel tegevuste üldistamisel tuua välja sarnasusi ja erinevusi. Tartu ja Tallinna sarnasteks tegevusteks on jalgrattavõrgustiku arendamine, sõidukiiruste piiramine vastavalt olukordadele, koolide kergliiklusteede ohutumaks muutmine, parkimiskohtade tagamine, jalgrattateede ja kergliiklusteede hoolduse (sh talihoolduse) tagamine. Antud tegevused olid sarnased ka Kopenhaageni ja Helsingi jalgrattastrateegiate tegevustega. Erinevused seisnesid ohutustarvikute jagamises ja jalgratturite teavitamisest linnaliikluses, mis olid välja toodud ainult Tartu jalgrattastrateegias. Kopenhaageni ja Helsingi jalgrattastrateegiast saavad Tartu ja Tallinn võtta eeskujuks järgnevaid tegevusi: tihendada koostööd politseiga, et trahvida jalgrattateedel parkijaid, tagada valgustus jalgrattateedel ning kasutada uuenduslikku lahendust fooridel ooteaja lühendamiseks. Selleks, et Eesti linnad saaksid erinevaid tegevusi efektiivselt ellu viia, tuleb suurendada investeeringuid antud valdkonda. Ühtse jalgrattaliikluse edendamiseks ja planeerimiseks Eestis oleks vajalik uuendada antud valdkonna planeerimisjuhendeid või luua ühtne metoodika jalgrattastrateegiate koostamiseks, kuhu saab vajadusel sisse tuua uuenduslikke eesmärke ja tegevusi teiste riikide näitel.In Estonia, Tallinn and Tartu, there is an increase in motor vehicles, but for better commuting conditions in the city there has to be focus on cycling, thus Tartu and Tallinn have created cycling strategies. This Bachelor's thesis goal is to analyze Tartu and Tallinn city cycling strategies using indicators compaired to Copenhagen and Helsinki cycling strategies. Chosen indicators for the analysis are following- safety, comfort, coherence, directness and attractiveness. Thesis concluded that since the city cycling strategy's goals and activities vary between destinations due to their city characteristics (and stage) then it was more difficult to compare the strategies than expected. Yet it was possible to conclude similarities and differences in strategies considering the indicators. Similarities in Tartu and Tallinn cycling strategies are following: cycling infrastructure development, speed reductions based on conditions, safety focus on school districts, having sufficient cycling parking lots and focus on infrastructure year around maintenance work. These actions were similar in Copenhagen and Helsinki cycling strategies. Differences in cycling strategies were following: safety equipment distribution and communication/ raising awareness of cyclists on the road (which was only brought out in Tartu's strategy). Copenhagen and Helsinki cycling strategies can be used and would benefit Tartu and Tallinn strategies in following areas: closer cooperation with Police, who can focus more on cars parked on cycling roads, better infrastructure on cycling street lights and use new technologies on traffic lights which reduce the waiting time for cyclists. Thesis found that in order to Estonain cities to implement actions related to cycling transport, there is a need to have more investments in the area. Estonian cities would benefit from country level created methodologies which direct the cities to create holistic cycling strategies

Implementing Organic Food in the Gindergardens of Tartu - problems and opportunities

Tänaseks kasutavad juba väga mitmed Tartu linna lasteaiad toidukordadel mahetoodangut. Lapseeas õigesti toitumine on väga tähtis, sest lapseeas kujunevad välja toitumisharjumused. Samuti on lapse kehamass küllaltki väike ning seetõttu on lastel oht saada tavatoidust suuremas koguses pestitsiide ja toksiine, kui on lubatud. Uurimistöö eesmärgiks oli selgeks teha peamised kitsaskohad mahetoidu kasutuselevõtul Tartu linna lasteaedades ja pakkuda ideid nende ületamiseks. Selleks, et uurida missugused on peamised probleemid ja kitsaskohad mahetoidu kasutuselevõtul lasteaedades, küsitleti kõiki Tartu linna lasteaedu. Tänaseks on paljud lasteaiad mahetoodangust teadlikud ja nõustuvad, et see on tervisele kasulikum kui tavatoit. Küsitlusest selgus, et 50% Tartu linna lasteaedadest juba kasutavad mahetoodangut. 40% lasteaedadest leidsid, et nad on valmis hakkama mahetoodangut pakkuma. Samuti viidi läbi küsitlus Tõrukese ja Pääsupesa lasteaia lapsevanematega, mille eesmärgiks oli välja selgitada lapsevanemate teadlikkus mahetoidu kasulikkusest ning valmisolek suurendada toidukorra päevamaksumust ühe lapse kohta. Uurimistöö maksimaalseks tulemuseks intervjueeriti Pääsupesa lasteaia direktorit Jana Pillmanni ja Tõrukese lasteaia juhatajat Kai Kikkast. Personali tagasiside abil saadi teada, missugused on peamised probleemid mahetoiduga alustamisel ning mida on vaja teada mahetoiduga alustamiseks. Kahe intervjueeritud lasteaia personali sõnul on suurimateks takistusteks mahetoidu kasutuselevõtul lasteaias mahetoorainete kättesaadavus, tooraine hind ning logistiline pool. Töö autor pakub käesolevas töös lasteaedadele mahetoidu kastususelevõtul tekkivatele probleemidele omapoolseid lahendusi.By today, many of the kindergartens in Tartu have included organic food into their menus. Eating right as a child is extremely important, because that’s when eating habits are formed. Also, because the child’s body is smaller, they are at risk of consuming more pesticides and toxins than is allowed. The goal of this research was to find out the main factors inhibiting the usage of organic food in Tartu kindergartens and proposing ideas to overcome those factors. 41 out of 40 kindergartens in Tartu were queried in order to find out what are the main reasons behind not using organic food. Most of the kindergartens are aware of organic food and agree that it is required for the health of the children and more beneficial than regular food. The research found that, 50% of the kindergartens in Tartu already use at least a little bit of organic food. It was also found out that 40% would be willing to include organic food into their menus. At the Tõruke and Pääsupesa kindergartens a query was also conducted amongst parents, which had a total of 109 participants. The goal was to find out the knowledge level of the parents regarding the benefits of organic food and the willingness to increase the price paid for meals. For the maximum effectiveness of this research, the director of the Pääsupesa kindergarten, Jana Pillmann and manager of the Tõruke kindergarten, Kai Kikkas, were also queried. Thanks to the feedback given by the kindergarten staff, it was found out what are the main problems that you need to know when trying to include organic food into the menus. The author of the research offers the kind

Molecular classification of uterine leiomyomas by genome-wide methods

Uterine leiomyomas, often called fibroids, are highly common tumors arising from smooth muscle cells of the myometrium. Whereas cancers have the ability to metastasize, leiomyomas are benign tumors that grow only locally. Nevertheless, leiomyomas frequently cause a variety of health complications, including abdominal pain, abnormal menstrual bleeding, and impaired fertility. Leiomyomas are the leading indication for hysterectomy worldwide, and pose a significant socio-economic impact. Despite their major public health impact, this disease attracts relatively little research. Epidemiological and molecular studies have indicated that, in the etiology of leiomyomas, genetic factors play a central role. Early cytogenetic studies revealed that approximately half of all leiomyomas display non-random chromosomal abnormalities such as high mobility group AT-hook 2 (HMGA2) gene translocations. Furthermore, family-based linkage studies revealed that germline mutations in the fumarate hydratase (FH) gene result in high penetrance susceptibility to uterine leiomyomas. Sporadic leiomyomas, however, rarely harbor FH mutations and the majority lack chromosomal abnormalities, suggesting that some driver genes remain undiscovered. Recent advances in sequencing technologies have made it possible to examine tumor genomes on a previously unprecedented scale. The aim of this thesis was to characterize the molecular underpinnings of uterine leiomyomas by the use of genome-wide methods such as massively parallel sequencing technology and gene expression microarrays. Using exome sequencing, we discovered that 71% of leiomyomas display localized mutations in the mediator complex subunit 12 (MED12) gene, making it their most commonly mutated gene. Furthermore, with whole-genome sequencing, we discovered that a subset of leiomyomas display highly complex chromosomal rearrangements, ones previously undetectable by conventional cytogenetic techniques. These rearrangements closely resembled chromothripsis, a phenomenon in which one or a few chromosomes are shattered into multiple pieces and randomly stitched together in a single event. We also found these events to have occurred multiple times, and some had resulted in genetic changes with a selective value, such as collagen type IV alpha 5 chain and collagen type IV alpha 6 chain (COL4A5-COL4A6) deletions. Patients affected by leiomyomas frequently harbor multiple distinct tumor nodules. Whereas the majority of studies have proposed that each leiomyoma arises independently, we found some leiomyomas to display identical chromosomal abnormalities, suggesting a common clonal origin. Whole-genome sequencing of clonally related leiomyomas revealed intratumor genetic heterogeneity suggestive of a branching model of tumor growth. Furthermore, we also discovered DEP domain containing 5 (DEPDC5) as a novel tumor suppressor gene, acting as a secondary driver gene in a subset of leiomyomas. Our integrative analyses demonstrated that specific genetic defects were the major determinants of expression changes in leiomyomas. Our observations indicate that at least four molecular subtypes exist: leiomyomas harboring a MED12 hotspot mutation, HMGA2 overexpression, FH inactivation, or COL4A5-COL4A6 deletion. We also detected subtype-specific expression differences in key tumorigenic pathways, including Wnt/β-catenin, Prolactin, IGF-1, and NRF2 signaling. Using genome-wide methods in this thesis work, we have discovered several novel molecular defects that underlie leiomyoma etiology. These studies emphasize the importance of stratification in leiomyoma research and offer a set of candidate biomarkers that may facilitate the molecular classification of uterine leiomyomas. Millions of women suffer from uterine leiomyomas, and the ability to classify each lesion should pave the way towards personalized treatments.Myom är godartade tumörer av glattmuskelceller som växer i livmodern. Kraftiga blödningar och smärtor är de vanligaste symptomen. En del kvinnor kan även bli infertila av myom. Hysterektomi är för tillfället den vanligaste och effektivaste operationen för myom. Trots deras kliniska och socioekonomiska konsekvenser, undersöks dessa tumörer relativt lite. Tidigare studier har visat att genetiska faktorer spelar en central roll i uppkomsten av myom. Undersökningar med hjälp av cytogenetik har visat att ungefär hälften av myom har kromosomavvikelser, såsom translokationer av genen high mobility group AT-hook 2 (HMGA2). Genetisk kopplingsanalys identifierade att ärftliga mutationer i genen fumarate hydratase (FH) är förknippade med en hög risk för myom. Sporadiska myom har dock sällan somatiska FH mutationer och majoriteten saknar kromosomavvikelser, vilket tyder på att en del gen-mutationer är oupptäckta. Framsteg inom sekvenseringsteknologin har gjort det möjligt att sekvensera människors hela genom mycket billigare och på en kortare tid. Syftet med denna avhandling var att karakterisera de molekylära faktorerna som bidrar till utveckling av myom med hjälp av massiv parallell sekvensering och mikromatriser. Med exom-sekvensering upptäckte vi att 71% av myom har specifika mutationer i genen mediator complex subunit 12 (MED12). Med genom-sekvensering upptäckte vi att en del myom har väldigt komplexa kromosomavvikelser ( chromothripsis ) som har uppstått på en och samma gång. En del av dessa kromosomavvikelser hade resulterat i specifika genetiska förändringar, såsom deletioner i generna collagen type IV alpha 5 chain och collagen type IV alpha 6 chain (COL4A5-COL4A6). Patienter som drabbas av myom har oftast flera myom i livmodern. Även om de flesta studier indikerar att varje myom uppstår självständig, så upptäckte vi att vissa myom kan ha identiska kromosomavvikelser, vilket tyder på att flera myom kan ha ett gemensamt ursprung. Dessutom upptäckte vi att genen DEP domain containing 5 (DEPDC5) har en sekundär roll i tillväxten av sådana myom. Vi upptäckte att specifika genetiska mutationer leder till unika genuttrycks mönster i myom. Våra observationer indikerar att åtminstone fyra molekylära underklasser av myom existerar: myom med mutationer i MED12, myom med överuttryck av HMGA2, myom med inaktivering av FH, och myom med deletioner i COL4A5 och COL4A6. Vi upptäckte att dessa underklasser har unika genuttrycks mönster i Wnt/β-catenin, prolaktin, IGF-1, och Nrf2 signalering. Med hjälp av dessa nya teknologier har vi nu upptäckt flera nya molekylära faktorer som bidrar till uppkomsten och tillväxten av myom. Dessa studier betonar betydelsen av att klassificera myom på molekyl-nivå, och vi identifierade potentiella biomarkörer som kan underlätta denna klassificering. Miljontals kvinnor drabbas av myom, och förmågan att klassificera myom kommer att förbättra utvecklingen av behandlingar mot denna vanliga sjukdom

Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations

Germline; Tumour-only sequencingLínia germinal; Seqüenciació només de tumorsLínea germinal; Secuenciación solo de tumorsBackground The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. Methods We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and ‘on-tumour’ status (established tumour-gene association). Results Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was <2%. Conclusion Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2, (iii) definition of a set of seven ‘most actionable’ cancer-susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6 and RET) in which germline follow-up is recommended regardless of tumour type.This work was supported by the European Society for Medical Oncology (no grant number)

Lung metastases and subsequent malignant transformation of a fumarate hydratase-deficient uterine leiomyoma

Uterine leiomyomas, or fibroids, are very common smooth muscle tumors. Their potential to metastasize or transform into leiomyosarcomas is extremely low. Here, we report a patient who underwent hysterectomy due to a large leiomyoma and who was diagnosed with pulmonary tumors seven and nine years later. Histopathological re-evaluation confirmed the cellular leiomyoma diagnosis for the uterine tumor, whereas the pulmonary tumors met the diagnostic criteria of a leiomyosarcoma. Whole-exome sequencing revealed very similar mutational profiles in all three tumors, including a somatic homozygous deletion in a rare, but well-established leiomyoma driver gene FH. Tumor evolution analysis confirmed the clonal origin of all three tumors. In addition to mutations shared by all three tumors, pulmonary tumors harbored additional alterations affecting e.g. the cancer associated genes NRG1 and MYOCD. The second pulmonary leiomyosarcoma harbored additional changes, including a mutation in FGFR1. In global gene expression profiling, the uterine tumor showed similar expression patterns as other FH-deficient leiomyomas. Taken together, this comprehensive molecular data supports the occasional metastatic capability and malignant transformation of uterine leiomyomas. Further studies are required to confirm whether FH-deficient tumors and/or tumors with cellular histopathology have higher malignant potential than other uterine leiomyomas.Peer reviewe

3 ' RNA and whole-genome sequencing of archival uterine leiomyomas reveal a tumor subtype with chromosomal rearrangements affecting either HMGA2, HMGA1, or PLAG1

Uterine leiomyomas, or fibroids, are very common smooth muscle tumors that arise from the myometrium. They can be divided into distinct molecular subtypes. We have previously shown that 3'RNA-sequencing is highly effective in classifying archival formalin-fixed paraffin-embedded (FFPE) leiomyomas according to the underlying mutation. In this study, we performed 3'RNA-sequencing with 111 FFPE leiomyomas previously classified as negative for driver alterations in mediator complex subunit 12 (MED12), high mobility group AT-hook 2 (HMGA2), and fumarate hydratase (FH) by Sanger sequencing and immunohistochemistry. This revealed 43 tumors that displayed expression features typically seen in HMGA2-positive tumors, including overexpression of PLAG1. We explored 12 such leiomyomas by whole-genome sequencing to identify their underlying genomic drivers and to evaluate the feasibility of detecting chromosomal driver alterations from FFPE material. Four tumors with significant HMGA2 overexpression at the protein-level served as controls. We identified chromosomal rearrangements targeting either HMGA2, HMGA1, or PLAG1 in all 16 tumors, demonstrating that it is possible to detect chromosomal driver alterations in archival leiomyoma specimens as old as 18 years. Furthermore, two tumors displayed biallelic loss of DEPDC5 and one tumor harbored a COL4A5-COL4A6 deletion. These observations suggest that instead of only HMGA2-positive leiomyomas, a distinct leiomyoma subtype is characterized by rearrangements targeting either HMGA2, HMGA1, or PLAG1. The results indicate that the frequency of HMGA2-positive leiomyomas may be higher than estimated in previous studies where immunohistochemistry has been used. This study also demonstrates the feasibility of detecting chromosomal driver alterations from archival FFPE material.Peer reviewe

3′RNA Sequencing Accurately Classifies Formalin-Fixed Paraffin-Embedded Uterine Leiomyomas

Uterine leiomyomas are benign smooth muscle tumors occurring in 70% of women of reproductive age. The majority of leiomyomas harbor one of three well-established genetic changes: a hotspot mutation in MED12, overexpression of HMGA2, or biallelic loss of FH. The majority of studies have classified leiomyomas by complex and costly methods, such as whole-genome sequencing, or by combining multiple traditional methods, such as immunohistochemistry and Sanger sequencing. The type of specimens and the amount of resources available often determine the choice. A more universal, cost-effective, and scalable method for classifying leiomyomas is needed. The aim of this study was to evaluate whether RNA sequencing can accurately classify formalin-fixed paraffin-embedded (FFPE) leiomyomas. We performed 3′RNA sequencing with 44 leiomyoma and 5 myometrium FFPE samples, revealing that the samples clustered according to the mutation status of MED12, HMGA2, and FH. Furthermore, we confirmed each subtype in a publicly available fresh frozen dataset. These results indicate that a targeted 3′RNA sequencing panel could serve as a cost-effective and robust tool for stratifying both fresh frozen and FFPE leiomyomas. This study also highlights 3′RNA sequencing as a promising method for studying the abundance of unexploited tissue material that is routinely stored in hospital archives

Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.&lt;p&gt;&lt;/p&gt; Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.&lt;p&gt;&lt;/p&gt; Setting: European clinical gynecology centers.&lt;p&gt;&lt;/p&gt; Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.&lt;p&gt;&lt;/p&gt; Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.&lt;p&gt;&lt;/p&gt; Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.&lt;p&gt;&lt;/p&gt; Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.&lt;p&gt;&lt;/p&gt; Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids