216 research outputs found
Mapping and sequencing of structural variation from eight human genomes
- Author
- Alkan C
- Altshuler DA
- ANTONACCI FRANCESCA
- Brand A
- Bruhn L
- Chen L
- Cheng Z
- Cooper GM
- David R
- Donahue WF
- Dorschner M
- Ebling HM
- Eichler EE
- Gillett W
- Graves T
- Gustafson E
- Hansen N
- Haugen E
- Hayden HS
- Kaul R
- Kidd JM
- Korn JM
- Malig M
- McCarroll SA
- McKernan K
- Mullikin JC
- Newman TL
- Nickerson DA
- Olson MV
- Peiffer DA
- Phelps KA
- Sampas N
- Saranga D
- Schwartz D
- Smith DR
- Smith JD
- Stamatoyannopoulos J
- Tao W
- Teague B
- Tsang P
- Tusneem N
- Tüzün E
- Weaver M
- Wilson RK
- Yamada NA
- Zerr T
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2008
- Field of study
Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale - particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone- based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high- resolution sequence map of human structural variation - a standard for genotyping platforms and a prelude to future individual genome sequencing projects
Fifteen-month follow up of an assertive community treatment program for chronic patients with mental illness
- Author
- A Udechuku
- AP Association
- B Angell
- C Harvey
- CM Coldwell
- EJ Nieves
- GB Teague
- GJ McHugo
- H Killaspy
- HJ Kim
- Ho-Jun Seo
- HS Park
- J Ito
- JE Overall
- Jong-Hyun Jeong
- K Horiuchi
- LI Stein
- M Cosden
- M Marshall
- MJ Oh
- N Meisler
- OK Yang
- P Harrison-Read
- PB Gold
- S Sytema
- Seung-Chul Hong
- SM Essock
- SY Min
- T Burns
- Tae-Won Kim
- YH Kim
- Young-Hee Kim
- YR Kim
- Yura Kim
- Z Russinova
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Epicardial adipose excision slows the progression of porcine coronary atherosclerosis
- Author
- A Matsumoto
- AA Arce-Esquivel
- Arturo A Arce-Esquivel
- AVMA Panel on Euthanasia
- B Tamarappoo
- DM Ouwens
- G Iacobellis
- GA Payne
- Harold S Sacks
- HS Sacks
- HS Sacks
- HS Sacks
- Institute for Laboratory Animal Research
- J Ding
- Jack H Boyd
- James P Byrd
- JD Horton
- JK Damas
- JM Edwards
- John N Fain
- Kyle A Schultz
- L Lee
- M Dyson
- M Greif
- M Harold Laughlin
- M Philippova
- M Sturek
- Michael Sturek
- Mikaela L McKenney
- MK Owen
- Mouhamad Alloosh
- P Iozzo
- R Tanaka
- SA Bustin
- Shawn D Teague
- SN Verhagen
- T Kodama
- T Mazurek
- T Takeuchi
- VY Cheng
- XY Zhu
- ZP Neeb
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed colorectal cancer: the prospective Streamline C trial
- Author
- Beare S
- Bhatnagar G
- Blunt D
- Boavida P
- Bridgewater J
- Clarke CS
- Duggan M
- Ellis S
- Glynne-Jones R
- Goh V
- Groves AM
- Halligan S
- Hameeduddin A
- Janes SM
- Johnston EW
- Koh D-M
- Mallett S
- Miles A
- Morris S
- Morton A
- Navani N
- O'Donohue J
- Oliver A
- Padhani AR
- Pardoe H
- Patel U
- Punwani S
- Quinn L
- Rafiee H
- Reczko K
- Rockall AG
- Shahabuddin K
- Sidhu HS
- Streamline investigators
- Taylor SA
- Teague J
- Thaha MA
- Train M
- van Ree K
- Wijeyekoon S
- Publication venue
- Elsevier
- Publication date
- 11/02/2019
- Field of study
Background: Whole-body magnetic resonance imaging(WB-MRI) may be an alternative to multi-modality staging of colon cancer but its relative diagnostic accuracy, effect on staging times, test number, cost, and impact on treatment decisions are unknown. We undertook a prospective multicentre cohort study to address this (ISRCTN43958015).
Methods: We recruited from 16 English hospitals. Eligible patients were 18 years or older, with newly diagnosed colon cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete. The multi-disciplinary team (MDT) recorded its first treatment decision based on standard investigations, then the alternate WB-MRI staging pathway (WB-MRI plus any additional tests generated), and finally on all tests combined. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12-months. Differences in treatment decisions, staging time, test number, and costs were secondary outcomes.
Findings: 299 patients completed the trial; 68 (23%) had metastasis at baseline. The WB-MRI pathway was 68% (95% CI 56 to 78) sensitive, not significantly different from standard pathways (63% [51 to 74]), a 4% (-5 to 13) difference, p=0.508. Specificity was not significantly different (95% [92 to 97], vs. 94% [90 to 96]). Agreement with the MDT final treatment decision was 96% and 95% for WB-MRI and standard pathways respectively. Time to complete staging was significantly shorter for WB-MRI (8 days [6 to 9] vs. 13 days [11 to 15]), a 5-day (3 to 7) difference. WB-MRI pathways required significantly fewer tests (median 1 [1 to 1] vs. 2 [2 to 2]), a difference of 1 (1 to 1). Mean per-patient staging costs were £216 and £285 for WB-MRI and standard pathways respectively.
Interpretation: WB-MRI staging pathways are as accurate as standard pathways, but reduce tests, staging time, and cost
Diagnostic accuracy of whole-body MRI versus standard imaging pathways for metastatic disease in newly diagnosed non-small-cell lung cancer: the prospective Streamline L trial
- Author
- Ball S
- Beare S
- Bhatnagar G
- Bhowmik A
- Boavida P
- Bridgewater J
- Clarke CS
- Duggan M
- Ellis S
- Glynne-Jones R
- Goh V
- Groves AM
- Halligan S
- Hameeduddin A
- Janes SM
- Johnston EW
- Koh D-M
- Lock S
- Mallett S
- Miles A
- Morris S
- Morton A
- Navani N
- O'Shaughnessy T
- Oliver A
- Padhani AR
- Prezzi D
- Punwani S
- Quinn L
- Rafiee H
- Reczko K
- Rockall AG
- Russell P
- Sidhu HS
- Streamline investigators
- Strickland N
- Tarver K
- Taylor SA
- Teague J
- Publication venue
- Publication date
- 01/01/2019
- Field of study
BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC. METHODS: The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete. FINDINGS: Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37-63) for WB-MRI and 54% (41-67) for standard pathways, a difference of 4% (-7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88-96]) and standard pathways (95% [91-98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12-14]) than for the standard pathway (19 days [17-21]); a 6-day (4-8) difference. The number of tests required was similar WB-MRI (one [1-1]) and standard pathways (one [1-2]). Mean per-patient costs were £317 (273-361) for WBI-MRI and £620 (574-666) for standard pathways. INTERPRETATION: WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs. FUNDING: UK National Institute for Health Research
Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV
- Author
- Aarrestad TK
- Aarup Petersen H
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abercrombie D
- Acharya H
- Acosta D
- Acosta JG
- Adam W
- Adams E
- Adams MR
- Adams T
- Adloff C
- Adzic P
- Agapitos A
- Agarwal G
- Aggleton R
- Agram J-L
- Aguilar-Benitez M
- Ahmad A
- Ahmad M
- Ahmed A
- Ahuja S
- Aime C
- Akchurin N
- Akgun B
- Akpinar A
- Albajar C
- Albergo S
- Albert A
- Albrow M
- Alcaraz Maestre J
- Aldaya Martin M
- Aldá Júnior WL
- Aleksandrov A
- Alexander J
- Alhusseini M
- Alimena J
- Alison J
- Allen B
- Almond J
- Alvarez Gonzalez B
- Alverson G
- Alves GA
- Aly R
- Alyari M
- Amapane N
- Amendola C
- Amin N
- Amram O
- Amsler C
- Anagnostou G
- Andrea J
- Andreev V
- Andreev Y
- Andrews MB
- Androsov K
- Antchev G
- Antunovic Z
- Apanasevich L
- Apollinari G
- Appelt E
- Apresyan A
- Apyan A
- Araujo M
- Arcaro D
- Arcidiacono R
- Arenton MW
- Argiro S
- Arneodo M
- Aruta C
- Asavapibhop B
- Asawatangtrakuldee C
- Asenov P
- Asghar MI
- Asilar E
- Askew A
- Asmuss P
- Aspell P
- Atakisi IO
- Atanassov I
- Ather MW
- Attikis A
- Auffray E
- Aushev T
- Auzinger G
- Avati V
- Avery P
- Avila C
- Awais A
- Awan MIM
- Ayala E
- Ayala G
- Aydogmus Sen F
- Azarkin M
- Azhgirey I
- Aziz T
- Azzi P
- Azzurri P
- Baarmand MM
- Babaev A
- Babounikau I
- Bacchetta N
- Bachiller I
- Bachtis M
- Backhaus M
- Baden A
- Baechler J
- Baginyan A
- Bagliesi G
- Bahinipati S
- Baillon P
- Bainbridge R
- Bakas G
- Bakhshiansohi H
- Bakirci MN
- Baldenegro Barrera C
- Ball AH
- Ban Y
- Band R
- Bandyopadhyay H
- Banerjee S
- Banerjee S
- Bansal S
- Barbagli G
- Barberis E
- Bargassa P
- Baringer P
- Barnes VE
- Barney D
- Baron O
- Barrio Luna M
- Bartek R
- Bartosik N
- Bartók M
- Bastos D
- Battilana C
- Baty A
- Bauer G
- Bauerdick LAT
- Baxter S
- Bayshev I
- Bean A
- Beauceron S
- Beaudette F
- Becerril Gonzalez H
- Bechtel J
- Bedoya CF
- Beghin D
- Behera PK
- Behera SC
- Behnke O
- Bein S
- Belchior Batista Das Chagas E
- Belforte S
- Bell KW
- Bellan R
- Belloni A
- Bellora A
- Belyaev A
- Belyaev A
- Benaglia A
- Benato L
- Bencze G
- Bendavid J
- Benecke A
- Benelli G
- Beni N
- Benitez JF
- Benussi L
- Berardi V
- Berenguer Antequera J
- Beretvas A
- Bergauer T
- Berger P
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- Beri SB
- Bermúdez Martínez A
- Bernardes CA
- Bernet C
- Berretti M
- Berry D
- Berryhill J
- Bertacchi V
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- Beschi A
- Bhal E
- Bhardwaj A
- Bharti M
- Bhat MA
- Bhat PC
- Bhatnagar V
- Bhattacharya R
- Bhattacharya S
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- Bheesette S
- Bhowmik D
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- Bhyun JH
- Bi R
- Bialkowska H
- Bianchini L
- Bianco M
- Bianco S
- Biasini M
- Biino C
- Bilei GM
- Bilin B
- Bin Anuar AA
- Bisello D
- Black K
- Blekman F
- Blinov V
- Bloch D
- Bloch P
- Bloom K
- Bluj M
- Blumenfeld B
- Boccali T
- Bocci A
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- Boletti A
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- Carrillo Montoya CA
- Carrillo Moreno S
- Cartiglia N
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- Chernyavskaya N
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- Cheung HWK
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- CMS Collaboration<sup>†</sup>
- Cockerill DJA
- Coelho E
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- Cole JE
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- Collard C
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- Connor P
- Consuegra Rodríguez S
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- Coubez X
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- Cousins R
- Covarelli R
- Cox B
- Cox PT
- Cranshaw DJ
- Creanza D
- Cremonesi M
- Cristella L
- Csanád M
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- Cumalat JP
- Cummings G
- Cussans D
- Cutts D
- Czellar S
- D'Alessandro R
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- D'Enterria D
- D'Hondt J
- Da Costa EM
- Da Rold A
- Da Silveira GG
- Dabrowski A
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- Dalchenko M
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- Damarseckin S
- Damgov J
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- Darwish MR
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- Daskalakis G
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- Field RD
- Fienga F
- Fiergolski A
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- Finger M
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- Fiori F
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- Zghiche A
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- Zhu RY
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- Álvarez Fernández A
- Österberg K
- Özçelik Ö
- Široký J
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses
Pan-cancer analysis of whole genomes
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- The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium View Correspondence (jump link)
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- Publication venue
- Publication date
- 11/12/2019
- Field of study
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV
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- Özçelik Ö
- Publication venue
- Publication date
- 01/01/2018
- Field of study
A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe
Evidence for Top Quark Production in Nucleus-Nucleus Collisions
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- Álvarez Fernández A
- Özçelik Ö
- Publication venue
- Publication date
- 01/01/2019
- Field of study
Peer reviewe
Observation of the B-s(0) -> X(3872)phi Decay
- Author
- Aarrestad TK
- Aarup Petersen H
- Abbaneo D
- Abbiendi G
- Abbrescia M
- Abdullin S
- Abercrombie D
- Acharya H
- Acosta D
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- Publication venue
- Publication date
- 01/01/2020
- Field of study
Using a data sample of proton-proton collisions at root s = 13 TeV, corresponding to an integrated luminosity of 140 fb(-1) collected by the CMS experiment in 2016-2018, the B-s(0) -> X(3872)phi decay is observed. Decays into J/psi pi(+)pi(-) and K+K- are used to reconstruct, respectively, the X(3872) and phi. The ratio of the product of branching fractions B[B-s(0) -> X(3872)phi]B[X(3872) -> J/psi pi(+)pi(-)] to the product B[B-s(0) ->psi(2S)phi]B[psi(2S) -> J/psi pi(+)pi(-)] is measured to be [2.21 +/- 0.29(stat) +/- 0.17(syst)]%. The ratio B[B-s(0) -> X(3872)phi]/B[B-0 -> X(3872)K-0] is found to be consistent with one, while the ratio B[B-s(0) -> X(3872)phi]/B[B+-> X(3872)K+] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B-0 and B(0)s meson decays compared to B+. The reported observation may shed new light on the nature of the X(3872) particle.Peer reviewe
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