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  1. Article ; Online: White matter microstructure relates to motor outcomes in myotonic dystrophy type 1 independently of disease duration and genetic burden

    Timothy R. Koscik / Ellen van der Plas / Laurie Gutmann / Sarah A. Cumming / Darren G. Monckton / Vincent Magnotta / Richard K. Shields / Peggy C. Nopoulos

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 15

    Abstract: Abstract Deficits in white matter (WM) integrity and motor symptoms are among the most robust and reproducible features of myotonic dystrophy type 1 (DM1). In the present study, we investigate whether WM integrity, obtained from diffusion-weighted MRI, ... ...

    Abstract Abstract Deficits in white matter (WM) integrity and motor symptoms are among the most robust and reproducible features of myotonic dystrophy type 1 (DM1). In the present study, we investigate whether WM integrity, obtained from diffusion-weighted MRI, corresponds to quantifiable motor outcomes (e.g., fine motor skills and grip strength) and patient-reported, subjective motor deficits. Critically, we explore these relationships in the context of other potentially causative variables, including: disease duration, elapsed time since motor symptom onset; and genetic burden, the number of excessive CTG repeats causing DM1. We found that fractional anisotropy (a measure of WM integrity) throughout the cerebrum was the strongest predictor of grip strength independently of disease duration and genetic burden, while radial diffusivity predicted fine motor skill (peg board performance). Axial diffusivity did not predict motor outcomes. Our results are consistent with the notion that systemic degradation of WM in DM1 mediates the relationship between DM1 progression and genetic burden with motor outcomes of the disease. Our results suggest that tracking changes in WM integrity over time may be a valuable biomarker for tracking therapeutic interventions, such as future gene therapies, for DM1.
    Keywords Medicine ; R ; Science ; Q
    Subject code 796
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Towards development of a statistical framework to evaluate myotonic dystrophy type 1 mRNA biomarkers in the context of a clinical trial.

    Adam Kurkiewicz / Anneli Cooper / Emily McIlwaine / Sarah A Cumming / Berit Adam / Ralf Krahe / Jack Puymirat / Benedikt Schoser / Lubov Timchenko / Tetsuo Ashizawa / Charles A Thornton / Simon Rogers / John D McClure / Darren G Monckton

    PLoS ONE, Vol 15, Iss 4, p e

    2020  Volume 0231000

    Abstract: Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3'-untranslated region of DMPK. Longer CTG expansions are associated with ...

    Abstract Myotonic dystrophy type 1 (DM1) is a rare genetic disorder, characterised by muscular dystrophy, myotonia, and other symptoms. DM1 is caused by the expansion of a CTG repeat in the 3'-untranslated region of DMPK. Longer CTG expansions are associated with greater symptom severity and earlier age at onset. The primary mechanism of pathogenesis is thought to be mediated by a gain of function of the CUG-containing RNA, that leads to trans-dysregulation of RNA metabolism of many other genes. Specifically, the alternative splicing (AS) and alternative polyadenylation (APA) of many genes is known to be disrupted. In the context of clinical trials of emerging DM1 treatments, it is important to be able to objectively quantify treatment efficacy at the level of molecular biomarkers. We show how previously described candidate mRNA biomarkers can be used to model an effective reduction in CTG length, using modern high-dimensional statistics (machine learning), and a blood and muscle mRNA microarray dataset. We show how this model could be used to detect treatment effects in the context of a clinical trial.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes

    Marc Ciosi / Alastair Maxwell / Sarah A. Cumming / Davina J. Hensman Moss / Asma M. Alshammari / Michael D. Flower / Alexandra Durr / Blair R. Leavitt / Raymund A.C. Roos / Peter Holmans / Lesley Jones / Douglas R. Langbehn / Seung Kwak / Sarah J. Tabrizi / Darren G. Monckton

    EBioMedicine, Vol 48, Iss , Pp 568-

    2019  Volume 580

    Abstract: Background: Huntington disease (HD) is caused by an unstable CAG/CAA repeat expansion encoding a toxic polyglutamine tract. Here, we tested the hypotheses that HD outcomes are impacted by somatic expansion of, and polymorphisms within, the HTT CAG/CAA ... ...

    Abstract Background: Huntington disease (HD) is caused by an unstable CAG/CAA repeat expansion encoding a toxic polyglutamine tract. Here, we tested the hypotheses that HD outcomes are impacted by somatic expansion of, and polymorphisms within, the HTT CAG/CAA glutamine-encoding repeat, and DNA repair genes. Methods: The sequence of the glutamine-encoding repeat and the proportion of somatic CAG expansions in blood DNA from participants inheriting 40 to 50 CAG repeats within the TRACK-HD and Enroll-HD cohorts were determined using high-throughput ultra-deep-sequencing. Candidate gene polymorphisms were genotyped using kompetitive allele-specific PCR (KASP). Genotypic associations were assessed using time-to-event and regression analyses. Findings: Using data from 203 TRACK-HD and 531 Enroll-HD participants, we show that individuals with higher blood DNA somatic CAG repeat expansion scores have worse HD outcomes: a one-unit increase in somatic expansion score was associated with a Cox hazard ratio for motor onset of 3·05 (95% CI = 1·94 to 4·80, p = 1·3 × 10−6). We also show that individual-specific somatic expansion scores are associated with variants in FAN1 (pFDR = 4·8 × 10-6), MLH3 (pFDR = 8·0 × 10−4), MLH1 (pFDR = 0·004) and MSH3 (pFDR = 0·009). We also show that HD outcomes are best predicted by the number of pure CAGs rather than total encoded-glutamines. Interpretation: These data establish pure CAG length, rather than encoded-glutamine, as the key inherited determinant of downstream pathophysiology. These findings have implications for HD diagnostics, and support somatic expansion as a mechanistic link for genetic modifiers of clinical outcomes, a driver of disease, and potential therapeutic target in HD and related repeat expansion disorders. Funding: CHDI Foundation. Keywords: Genetic association study, Somatic expansion, DNA repair, Huntington disease
    Keywords Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610 ; 572
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Management of Inherited Bleeding Disorders in Pregnancy (Green-top Guideline No. 71)

    S. Pavord / R. Rayment / B. Madan / A. Cumming / W. Lester / E. Chalmers / B. Myers / H. Maybury / C. Tower / R. A. Kadir

    Семейная медицина, Vol 0, Iss 6 (74), Pp 76-

    2017  Volume 101

    Abstract: Это руководство предназначено как для специалистов-гематологов, так и для акушеров, которые имеют опыт ведения беременных с нарушениями свертываемости крови. Кроме того, эти рекомендации могут быть полезными для анестезиологов в акушерстве и неонатологов. ...

    Abstract Это руководство предназначено как для специалистов-гематологов, так и для акушеров, которые имеют опыт ведения беременных с нарушениями свертываемости крови. Кроме того, эти рекомендации могут быть полезными для анестезиологов в акушерстве и неонатологов. Женщины, унаследовавшие нарушения свертываемости крови, могут подвергаться значительному риску кровотечения после выкидышей, абортов, дородовых процедур и родов. Они требуют индивидуального мультидисциплинарного специализированного ухода с перекрестной коммуникацией специалистов, в том числе анестезиологов и неонатологов при необходимости. Был достигнут прогресс в выявлении акушерских проблем у этих женщин и повышении уровня осведомленности об оказании медицинской помощи среди работников здравоохранения. Конкретные аспекты их ведения в акушерстве включают консультирование на этапе преконцепционной подготовки, пренатальную диагностику (ПНД), антенатальный, внутриутробный и послеродовой уход и немедленную помощь новорожденному.
    Keywords Medicine ; R
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher "PROFESSIONAL-EVENT" LLC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: COSMOS-UK

    H. M. Cooper / E. Bennett / J. Blake / E. Blyth / D. Boorman / E. Cooper / J. Evans / M. Fry / A. Jenkins / R. Morrison / D. Rylett / S. Stanley / M. Szczykulska / E. Trill / V. Antoniou / A. Askquith-Ellis / L. Ball / M. Brooks / M. A. Clarke /
    N. Cowan / A. Cumming / P. Farrand / O. Hitt / W. Lord / P. Scarlett / O. Swain / J. Thornton / A. Warwick / B. Winterbourn

    Earth System Science Data, Vol 13, Pp 1737-

    national soil moisture and hydrometeorology data for environmental science research

    2021  Volume 1757

    Abstract: The COSMOS-UK observation network has been providing field-scale soil moisture and hydrometeorological measurements across the UK since 2013. At the time of publication a total of 51 COSMOS-UK sites have been established, each delivering high-temporal ... ...

    Abstract The COSMOS-UK observation network has been providing field-scale soil moisture and hydrometeorological measurements across the UK since 2013. At the time of publication a total of 51 COSMOS-UK sites have been established, each delivering high-temporal resolution data in near-real time. Each site utilizes a cosmic-ray neutron sensor, which counts epithermal neutrons at the land surface. These measurements are used to derive field-scale near-surface soil water content, which can provide unique insight for science, industry, and agriculture by filling a scale gap between localized point soil moisture and large-scale satellite soil moisture datasets. Additional soil physics and meteorological measurements are made by the COSMOS-UK network including precipitation, air temperature, relative humidity, barometric pressure, soil heat flux, wind speed and direction, and components of incoming and outgoing radiation. These near-real-time observational data can be used to improve the performance of hydrological models, validate remote sensing products, improve hydro-meteorological forecasting, and underpin applications across a range of other scientific fields. The most recent version of the COSMOS-UK dataset is publically available at https://doi.org/10.5285/b5c190e4-e35d-40ea-8fbe-598da03a1185 (Stanley et al., 2021).
    Keywords Environmental sciences ; GE1-350 ; Geology ; QE1-996.5
    Subject code 550 ; 333
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Copernicus Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: The full carbon balance of a rewetted cropland fen and a conservation-managed fen

    Peacock, M / A. Burden / A. Cumming / A.J. Baird / C.D. Evans / F. Worrall / G. Pan / J. Holden / J. Kaduk / J. Williamson / J.G. Evans / L.M. Ridley / P.J. Chapman / R. Morrison / R.P. Grayson / S. Page / V. Gauci

    Agriculture, ecosystems & environment. 2019 Jan. 01, v. 269

    2019  

    Abstract: On a global scale, the release of greenhouse gases (GHG) from peatland drainage and cultivation are believed to account for ∼5% of estimated anthropogenic GHG emissions. Drainage generally leads to peat subsidence and extensive soil loss, resulting in a ... ...

    Abstract On a global scale, the release of greenhouse gases (GHG) from peatland drainage and cultivation are believed to account for ∼5% of estimated anthropogenic GHG emissions. Drainage generally leads to peat subsidence and extensive soil loss, resulting in a diminishing store of soil carbon (C). This is a challenge for maintaining drainage-based agriculture, as such practices will eventually lead to the loss of organic soils that arable cultivation depends on. The conversion of croplands on peat to semi-natural grasslands, alongside raising water tables, is one possible way to reduce the loss of these valuable C stores. Here, we report the net ecosystem carbon balances (NECB) of two lowland peatlands in East Anglia, south-east UK. One site is a relic conservation-managed fen on deep peat, subject to active hydrological management to maintain water levels, and dominated by Cladium and Phragmites sedge and reed beds, whilst the other is a former cropland that has been converted to seasonally-inundated grazed grassland. Despite occasionally experiencing severe water table drawdown, the conservation-managed fen was a strong C sink of -104 g C m−2 yr−1. In contrast, the grassland was a C source of 133 g C m−2 yr−1, with gaseous carbon dioxide (CO2) emissions being the main loss pathway, due to low water tables exposing the soil profile in summer. At each site, ditch emissions of CO2 were moderately large (22 and 37 g C m−2 yr−1), whilst ditch methane (CH4) emissions (0.2 and 1.8 g C m−2 yr−1) made a negligible contribution to the NECB, but are important when considering the ecosystem GHG balance in terms of CO2 equivalents. Excluding dissolved inorganic carbon (DIC), fluvial C losses were 6 g C m−2 yr−1 for the conservation-managed fen and 12 g C m−2 yr−1 for the former cropland, and were dominated by dissolved organic carbon (DOC). The small fluvial C loss is the result of both sites being hydrologically isolated from the surrounding agricultural landscapes. Although the partially re-wetted cropland was still acting as a net C source, our estimates suggest that seasonal rewetting has reduced net annual C losses to ∼20% of their former cropland values. Maintaining high water tables year round would potentially further reduce C losses, and shallow inundation might allow the return of wetland species such as Phragmites and Typha, perhaps as floating rafts.
    Keywords carbon dioxide ; Cladium ; cropland ; dissolved organic carbon ; drainage ; drawdown ; ecosystems ; grasslands ; greenhouse gas emissions ; greenhouse gases ; inorganic carbon ; methane ; organic soils ; peat ; peatlands ; Phragmites ; soil erosion ; soil profiles ; subsidence ; summer ; Typha ; water table ; United Kingdom
    Language English
    Dates of publication 2019-0101
    Size p. 1-12.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 602345-9
    ISSN 1873-2305 ; 0167-8809
    ISSN (online) 1873-2305
    ISSN 0167-8809
    DOI 10.1016/j.agee.2018.09.020
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift During the LIGO-Virgo Run O3a

    Collaboration, The LIGO Scientific / R.Abbott, the Virgo Collaboration / T.D.Abbott, / S.Abraham, / F.Acernese, / K.Ackley, / C.Adams, / R.X.Adhikari, / V.B.Adya, / C.Affeldt, / M.Agathos, / K.Agatsuma, / N.Aggarwal, / O.D.Aguiar, / A.Aich, / L.Aiello, / A.Ain, / P.Ajith, / G.Allen, /
    A.Allocca, / P.A.Altin, / A.Amato, / S.Anand, / A.Ananyeva, / S.B.Anderson, / W.G.Anderson, / S.V.Angelova, / S.Ansoldi, / S.Antier, / S.Appert, / K.Arai, / M.C.Araya, / J.S.Areeda, / M.Arene, / N.Arnaud, / S.M.Aronson, / Y.Asali, / S.Ascenzi, / G.Ashton, / M.Assiduo, / S.M.Aston, / P.Astone, / F.Aubin, / P.Aufmuth, / K.AultONeal, / C.Austin, / V.Avendano, / S.Babak, / P.Bacon, / F.Badaracco, / M.K.M.Bader, / S.Bae, / A.M.Baer, / J.Baird, / F.Baldaccini, / G.Ballardin, / S.W.Ballmer, / A.Bals, / A.Balsamo, / G.Baltus, / S.Banagiri, / D.Bankar, / R.S.Bankar, / J.C.Barayoga, / C.Barbieri, / B.C.Barish, / D.Barker, / K.Barkett, / P.Barneo, / F.Barone, / B.Barr, / L.Barsotti, / M.Barsuglia, / D.Barta, / J.Bartlett, / I.Bartos, / R.Bassiri, / A.Basti, / M.Bawaj, / J.C.Bayley, / M.Bazzan, / B.B'ecsy, / M.Bejger, / I.Belahcene, / A.S.Bell, / D.Beniwal, / M.G.Benjamin, / J.D.Bentley, / F.Bergamin, / B.K.Berger, / G.Bergmann, / S.Bernuzzi, / C.P.L.Berry, / D.Bersanetti, / A.Bertolini, / J.Betzwieser, / R.Bhandare, / A.V.Bhandari, / A.Bianchi, / J.Bidler, / E.Biggs, / I.A.Bilenko, / G.Billingsley, / R.Birney, / O.Birnholtz, / S.Biscans, / M.Bischi, / S.Biscoveanu, / A.Bisht, / G.Bissenbayeva, / M.Bitossi, / M.A.Bizouard, / J.K.Blackburn, / J.Blackman, / C.D.Blair, / D.G.Blair, / R.M.Blair, / F.Bobba, / N.Bode, / M.Boer, / Y.Boetzel, / G.Bogaert, / F.Bondu, / E.Bonilla, / R.Bonnand, / P.Booker, / B.A.Boom, / R.Bork, / V.Boschi, / S.Bose, / V.Bossilkov, / J.Bosveld, / Y.Bouffanais, / A.Bozzi, / C.Bradaschia, / P.R.Brady, / A.Bramley, / M.Branchesi, / J.E.Brau, / M.Breschi, / T.Briant, / J.H.Briggs, / F.Brighenti, / A.Brillet, / M.Brinkmann, / P.Brockill, / A.F.Brooks, / J.Brooks, / D.D.Brown, / S.Brunett, / G.Bruno, / R.Bruntz, / A.Buikema, / T.Bulik, / H.J.Bulten, / A.Buonanno, / D.Buskulic, / R.L.Byer, / M.Cabero, / L.Cadonati, / G.Cagnoli, / C.Cahillane, / Bustillo, J.Calder'on / J.D.Callaghan, / T.A.Callister, / E.Calloni, / J.B.Camp, / M.Canepa, / Santoro, G.Caneva / K.C.Cannon, / H.Cao, / J.Cao, / G.Carapella, / F.Carbognani, / S.Caride, / M.F.Carney, / G.Carullo, / T.L.Carver, / Diaz, J.Casanueva / C.Casentini, / J.Castaneda, / S.Caudill, / M.Cavaglia, / F.Cavalier, / R.Cavalieri, / G.Cella, / P.Cerd'a-Dur'an, / E.Cesarini, / O.Chaibi, / K.Chakravarti, / C.Chan, / M.Chan, / S.Chao, / P.Charlton, / E.A.Chase, / E.Chassande-Mottin, / D.Chatterjee, / M.Chaturvedi, / H.Y.Chen, / X.Chen, / Y.Chen, / H.-P.Cheng, / C.K.Cheong, / H.Y.Chia, / F.Chiadini, / R.Chierici, / A.Chincarini, / A.Chiummo, / G.Cho, / H.S.Cho, / M.Cho, / N.Christensen, / Q.Chu, / S.Chua, / K.W.Chung, / S.Chung, / G.Ciani, / P.Ciecielag, / M.Cie'slar, / A.A.Ciobanu, / R.Ciolfi, / F.Cipriano, / A.Cirone, / F.Clara, / J.A.Clark, / P.Clearwater, / S.Clesse, / F.Cleva, / E.Coccia, / P.-F.Cohadon, / D.Cohen, / M.Colleoni, / C.G.Collette, / C.Collins, / M.Colpi, / M.Constancio, / L.Conti, / S.J.Cooper, / P.Corban, / T.R.Corbitt, / I.Cordero-Carri'on, / S.Corezzi, / K.R.Corley, / N.Cornish, / D.Corre, / A.Corsi, / S.Cortese, / C.A.Costa, / R.Cotesta, / M.W.Coughlin, / S.B.Coughlin, / J.-P.Coulon, / S.T.Countryman, / P.Couvares, / P.B.Covas, / D.M.Coward, / M.J.Cowart, / D.C.Coyne, / R.Coyne, / J.D.E.Creighton, / T.D.Creighton, / J.Cripe, / M.Croquette, / S.G.Crowder, / J.-R.Cudell, / T.J.Cullen, / A.Cumming, / R.Cummings, / L.Cunningham, / E.Cuoco, / M.Curylo, / Canton, T.Dal / G.D'alya, / A.Dana, / L.M.Daneshgaran-Bajastani, / B.D'Angelo, / S.L.Danilishin, / S.D'Antonio, / K.Danzmann, / C.Darsow-Fromm, / A.Dasgupta, / L.E.H.Datrier, / V.Dattilo, / I.Dave, / M.Davier, / G.S.Davies, / D.Davis, / E.J.Daw, / D.DeBra, / M.Deenadayalan, / J.Degallaix, / Laurentis, M.De / S.Del'eglise, / M.Delfavero, / Lillo, N.De / Pozzo, W.Del / L.M.DeMarchi, / V.D'Emilio, / N.Demos, / T.Dent, / Pietri, R.De / Rosa, R.De / Rossi, C.De / R.DeSalvo, / Varona, O.de / S.Dhurandhar, / M.C.D'iaz, / M.Diaz-Ortiz, / T.Dietrich, / Fiore, L.Di / Fronzo, C.Di / Giorgio, C.Di / Giovanni, F.Di 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    Abstract: We search for gravitational-wave transients associated with gamma-ray bursts detected by the Fermi and Swift satellites during the first part of the third observing run of Advanced LIGO and Advanced Virgo (1 April 2019 15:00 UTC - 1 October 2019 15:00 ... ...

    Abstract We search for gravitational-wave transients associated with gamma-ray bursts detected by the Fermi and Swift satellites during the first part of the third observing run of Advanced LIGO and Advanced Virgo (1 April 2019 15:00 UTC - 1 October 2019 15:00 UTC). 105 gamma-ray bursts were analyzed using a search for generic gravitational-wave transients; 32 gamma-ray bursts were analyzed with a search that specifically targets neutron star binary mergers as short gamma-ray burst progenitors. We describe a method to calculate the probability that triggers from the binary merger targeted search are astrophysical and apply that method to the most significant gamma-ray bursts in that search. We find no significant evidence for gravitational-wave signals associated with the gamma-ray bursts that we followed up, nor for a population of unidentified subthreshold signals. We consider several source types and signal morphologies, and report for these lower bounds on the distance to each gamma-ray burst.
    Keywords covid19
    Publisher ArXiv
    Document type Article
    Database COVID19

    Kategorien

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