393 research outputs found
Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals
- Author
- Abou Jamra Rami
- Baysal Özlem
- Bosch Elisabeth
- Bruno Lucia Pia
- Capra Valeria
- Carter Lauren B
- Cogné Benjamin
- Cuscó Ivon
- De Marco Patrizia
- et al
- Granata Stefania
- Güse Esther
- Hartwich Dewi
- Holthöfer Laura
- Isidor Bertrand
- Kuismin Outi
- Marcelis Carlo
- Maroofian Reza
- Martinez-Agosto Julian A
- Maystadt Isabelle
- Ognibene Marzia
- Pinto Anna Maria
- Platzer Konrad
- Popp Bernt
- Renieri Alessandra
- Scala Marcello
- Skinner Cindy
- Valenzuela Irene
- van der Sluijs Pleuntje J
- van Haeringen Arie
- Wieczorek Dagmar
- Zweier Markus
- Publication venue
- Elsevier
- Publication date
- 01/11/2023
- Field of study
Purpose:
Coffin-Siris and Nicolaides-Baraitser syndromes, are recognisable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort.
Methods:
Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlation, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays.
Results:
Neurodevelopmental delay with intellectual disability, muscular hypotonia and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, while non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD.
Conclusion:
This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated
Citrullinated glucose-regulated protein 78 is a candidate target for melanoma immunotherapy
- Author
- Publication venue
- 'Frontiers Media SA'
- Publication date
- 01/12/2022
- Field of study
IntroductionPost translational modification of proteins plays a significant role in immune recognition. In particular the modification of arginine to citrulline which is mediated by PAD enzymes is increased during cellular stress (autophagy) which permits the presentation of modified epitopes upon MHC class II molecules for recognition by CD4 T cells. Citrullination also occurs in tumour cells as a result of continuous environmental stresses and increased autophagy. We have shown in animal models the efficient stimulation of citrullinated epitope specific CD4 T cells resulting in dramatic elimination/regression of tumours. The ER chaperone glucose-regulated protein 78 (GRP78) is known to also be required for stress-induced autophagy and is directly linked to autophagosome formation. GRP78 is known to be highly expressed by many tumour types. In this study we investigate the potential of targeting citrullinated GRP78 for cancer therapy.MethodsA citrullinated GRP78 specific antibody was used to assess citrullinated GRP78 expression in murine and human tumour cells by flow cytometry. Five peptides were selected and used to vaccinate HLA transgenic mice and immune responses were characterised by ex vivo cytokine ELISpot assay. T cell repertoire in humans was assessed through proliferation assays and cytokine ELISpot assay. Citrullinated peptide was identified in murine B16 melanoma by mass spectrometry and the peptide vaccine was assessed for tumour therapy in a mouse melanoma model.ResultsWe show the identification CD4 T cell responses to one citrullinated GRP78 epitope that are restricted through HLA DP*0401 and HLA-DR*0101 alleles. This peptide is detected by mass spectrometry in B16 melanoma grown in vivo and citrulline specific CD4 responses to two peptides spanning this epitope mediate efficient therapy of established B16 melanoma tumours in HHDII/DP4 (p<0.0001) transgenic mouse model. Finally, we demonstrate the existence of a repertoire of responses to the citrullinated GRP78 peptide in healthy individuals (p=0.0023) with 13/17 (76%) individuals showing a response to this peptide.ConclusionWe propose that citrullinated GRP78 is a candidate tumour antigen and vaccination against citrullinated GRP78 may provide a promising tumour therapy approach
Genetic evidence of the association of DEAH-box helicase 37 defects with 46,XY gonadal dysgenesis spectrum
- Author
- Achermann
- Al-Zahrani
- Alejandro Martinez-Aguayo
- Alexander Augusto Lima Jorge
- Antonio Marcondes Lerário
- Assumpção
- Auton
- Berenice Bilharinho Mendonca
- Bleichert
- Brownstein
- Catherine Elizabeth Keegan
- Cheng
- Choudhury
- da Silva
- de Grouchy
- Domenice
- Eduardo Corrêa Costa
- Eggers
- Elaine Maria Frade Costa
- Eric Vilain
- Felipe Martins Elias
- Filomena Marino Carvalho
- Gomes
- Hayk Barseghyan
- Hirata
- Jankowsky
- Josso
- Jégou
- Koopman
- Leila Cristina Pedroso de Paula
- Lessel
- Luciani Renata Carvalho
- Marcantonio
- María Verónica Forclaz
- Miller
- Mills
- Mirian Yumi Nishi
- Naslavsky
- Nathalia Lisboa Gomes
- Ono
- Park
- Pearlman
- Philibert
- Regina Papazian
- Richards
- Rios-Rojas
- Robboy
- Rod Mitchell
- Sarafoglou
- Sathya
- Skinner
- Sorahia Domenice
- Suntharalingham
- Svingen
- Thatiana Evilen da Silva
- Thul
- Tian
- Uhlen
- Uhlén
- Publication venue
- 'The Endocrine Society'
- Publication date
- 09/07/2019
- Field of study
Prognostic benefit of surgical management in renal cell carcinoma patients with thrombus extending to the renal vein and inferior vena cava: 17-year experience at a single center
- Author
- A Bex
- A Haferkamp
- A Zisman
- B Ljungberg
- Chikara Ohyama
- D Bainbridge
- Daisuke Noro
- DC Vergho
- DG Skinner
- EH Lambert
- G Staehler
- H Miyake
- H Takeda
- Hiromi Murasawa
- HL Kim
- Itsuto Hamano
- JI Martinez-Salamanca
- K Vander Eeckt
- Kazuhisa Hagiwara
- LC Harshman
- LH Sobin
- M Al Otaibi
- M Tanaka
- Masaaki Oikawa
- MK O’Donohoe
- ML Blute
- MM Oken
- MT Gettman
- NG Cost
- PI Karakiewicz
- RJ Neves
- SB Edge
- Shingo Hatakeyama
- Takahiro Yoneyama
- Takuma Narita
- Takuya Koie
- Toshikazu Tanaka
- Yasuhiro Hashimoto
- Yoshimi Tanaka
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
A miRNA Signature of Prion Induced Neurodegeneration
- Author
- A Grimson
- A Krek
- A Schaefer
- AD Greenwood
- AK Leung
- B John
- BP Lewis
- C Riemer
- C Xiao
- CA Baker
- CA Baker
- Catherine Robertson
- Chelsey D. Goodman
- D Eletto
- DP Bartel
- E Wingender
- F Al-Shahrour
- G Estivill-Torrus
- G Robertson
- G Sorensen
- GP Sawiris
- GU Hoglinger
- HY Cheng
- J Bilen
- J Clinton
- J Kim
- J Kim
- J Schultz
- J Wu
- JC Huang
- JC Quinn
- JS Karres
- K Doh-ura
- K Schindowski
- KJ Bussey
- KL Jordan-Sciutto
- LP Lim
- M Gotz
- M Jeffrey
- M Jeffrey
- ME Klein
- N Vo
- PJ Skinner
- R Hellweg
- R Saba
- Reuben Saba
- Rhiannon L. C. H. Huzarewich
- S Booth
- S Oddo
- S Uchida
- S Vasudevan
- SB Prusiner
- Schahram Akbarian
- Stephanie A. Booth
- T Kitamoto
- T Liu
- T Mantamadiotis
- T Martinez
- TL Cuellar
- VG Tusher
- W Xiang
- WJ Lukiw
- WX Wang
- Publication venue
- Public Library of Science
- Publication date
- 01/01/2008
- Field of study
MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion–induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified
Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites
- Author
- Abukurah A.
- Acharya M.
- Agarwal A.
- Ahmad S.
- Al-Bander H.
- Al-Saghir F.
- Alas E.
- Albertazzi A.
- Alcázar de La Ossa J.
- Alfred H.
- Almeida F.
- Altobelli V.
- Alvarez Sandoval E.
- Amatya A.
- Anashkin V.
- Andrusev A.
- Andrés Ribes E.
- Ang K.
- Anger M.
- Aranda Verástegui F.
- Araújo S.
- Arbeit L.
- Arfeen S.
- Arias I.
- Arif F.
- Arkossy O.
- Arrieta J.
- Arruda J.
- Ashfaq A.
- Assefi A.
- Auricchio M.
- Avella F.
- Ayodeji O.
- Azer M.
- Baer H.
- Balkarova O.
- Bannister K.
- Bastos M.
- Batista P.
- Batlle D.
- Becker B.
- Belledonne M.
- Bentkowski W.
- Beresan H.
- Bernardo M.
- Berta K.
- Bhandari K.
- Bhatia D.
- Bidas K.
- Billiouw J.
- Block G.
- Block Geoffrey A.
- Blumenthal S.
- Bochicchio-Ricardelli T.
- Bolasco P.
- Borbas B.
- Boulechfar H.
- Bouman K.
- Brancaccio D.
- Brandi L.
- Braun J.
- Braun M.
- Bregman R.
- Brink H.
- Brosnahan G.
- Brown C.
- Brown E.
- Brunet P.
- Buerkert J.
- Burdmann E.
- Burnier M.
- Cambier-Dwelschauwers P.
- Cangiano-Rivera J.
- Cannella G.
- Capasso G.
- Capelli J.
- Cappelli G.
- Cardeal da Costa J.
- Carvalho A.
- Carvalho B.
- Cases A.
- Cavalieri T.
- Chaffin M.
- Charytan C.
- Cheng J.
- Chertow Glenn M.
- Chew Wong A.
- Chidester P.
- Choukroun G.
- Chow S.
- Cleveland W.
- Coll Piera E.
- Combe C.
- Cook M.
- Correa-Rotter R.
- Correa-Rotter Ricardo
- Cottiero R.
- Cotton J.
- Cournoyer S.
- Cozzolino M.
- Crouch T.
- Cruz-Valdez J.
- Csiky B.
- Culleton B.
- Culpepper M.
- Cunha P. D.
- Cusumano A.
- d'Avila D.
- Da Roza G.
- Daelemans R.
- Dalal S.
- Darwish R.
- Dasgupta I.
- Daugaard H.
- Davies M.
- Davies S.
- de Almeida Romão E.
- de Francesco Daher E.
- De Meester J.
- Deboni L.
- Dehmel Bastian
- Dejagere T.
- Del Valle E.
- DelGiorno T.
- Dellanna F.
- Denu-Ciocca C.
- Desmeules S.
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- Di Giulio S.
- Diamond S.
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- Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators
- Evenepoel P.
- Fadem S.
- Farina M.
- Fassett R.
- Fekete A.
- Felsenfeld A.
- Ferenczi S.
- Fernandez Lucas M.
- Ferrari P.
- Ferreira Filho S.
- Fessi H.
- Fiedler R.
- Finkelstein F.
- Fischer D.
- Floege J.
- Flöge Jürgen
- Fraenkel M.
- Frascà G.
- Frazao J.
- Friedman E.
- Friedman L.
- Frischmuth N.
- Galicia M.
- Galindo-Ramos E.
- Gallart C.
- Gandhi K.
- Garcia V.
- García F.
- García N.
- Garrote N.
- Gehr T.
- Gesualdo L.
- Gillies A.
- Gladish R.
- Goldberger S.
- Golden J.
- Goldfarb D.
- Goldman J.
- Goldsmith D.
- Gonzalez R.
- González M.
- Goodman William G.
- Gordan P.
- Graf H.
- Grandaliano G.
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- Gupta A.
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- Publication venue
- Publication date
- 01/01/2006
- Field of study
The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions.
The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness
of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence
were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density
and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that
the wood in the starch composites did not prevent water loss from the samples.Peer reviewe
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
- Author
- Aanei CM
- Abid MB
- Abramowitz MK
- Abu-Zaid A
- Afnan M
- Agarabi C
- Ahmad R
- Aizat WM
- Al-Farha AA
- Al-Lawama M
- Alanio A
- Alaux C
- Albiol J
- Albrecht DR
- Albuquerque LG
- Alimba CG
- Allardyce J
- Almeida GMF
- Alonso-Caneiro D
- Alper OM
- Amer SEDR
- Amiya E
- Ammerman BA
- Amorim RM
- An Q
- Andersen SU
- Aplin JD
- Argyropoulos C
- Armitage C
- Ascher DB
- Ashry M
- Asmann YW
- Assaeed AM
- Atack JM
- Atanasov AG
- Atchison DA
- Atkins GJ
- Atlas L
- Avery SV
- Avillach P
- Baade PD
- Backman L
- Badie C
- Bae T
- Baier D
- Baker CI
- Bakkach J
- Baldi A
- Ball E
- Bannon R
- Bansal A
- Bardot O
- Barnett AG
- Barraud P
- Basharat Z
- Basner M
- Batra J
- Baumert P
- Bazanova OM
- Beale A
- Beck CR
- Becker D
- Beddoe T
- Bell ML
- Benezeth Y
- Bengtsson-Palme J
- Berbesque C
- Berezikov E
- Bergsland N
- Berners-Price S
- Bernhardt P
- Berrevoet F
- Berry E
- Berthold M
- Bessa TB
- Beyene TJ
- Biedermann PHW
- Bijleveld E
- Billington C
- Birch J
- Bittner F
- Bitzer M
- Blakely RD
- Blanck O
- Blaskovich MAT
- Bleackley M
- Blombach F
- Blum R
- Boehme KA
- Boelaert M
- Bogdanos D
- Bonvin AMJJ
- Bosch C
- Bosch O
- Boudreau SA
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- Ziegler A
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- Zuberbier T
- Publication venue
- OXFORD UNIV PRESS
- Publication date
- 29/10/2019
- Field of study
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at root s = 8 TeV with the ATLAS detector (vol 75, 299, 2015)
- Author
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- Abbott B
- Abdallah J
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- Abramowicz H
- Abreu H
- Abreu R
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- Acharya BS
- Adam ER
- Adamczyk L
- Adams DL
- Adelman J
- Adomeit S
- Adye T
- Agatonovic-Jovin T
- Aguilar-Saavedra JA
- Agustoni M
- Ahlen SP
- Ahmadov F
- Aielli G
- Akerstedt H
- Akesson TPA
- Akimoto G
- Akimov AV
- Alberghi GL
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- Albrand S
- Alconada Verzini MJ
- Aleksa M
- Aleksandrov IN
- Alexa C
- Alexander G
- Alexandre G
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- Alimonti G
- Alio L
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- Allbrooke BMM
- Allison LJ
- Allport PP
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- Amaral Coutinho Y
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- Wosiek BK
- Wotschack J
- Woudstra MJ
- Wozniak KW
- Wu M
- Wu SL
- Wu X
- Wu Y
- Wyatt TR
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- Yao L
- Yao W-M
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- Yeletskikh I
- Yen AL
- Yildirim E
- Yildiz HD
- Yorita K
- Yoshida R
- Yoshihara K
- Young C
- Young CJS
- Youssef S
- Yu DR
- Yu J
- Yu J
- Yu JM
- Yuan L
- Yurkewicz A
- Yusuff I
- Zabinski B
- Zaidan R
- Zaitsev AM
- Zaman A
- Zambito S
- Zanello L
- Zanzi D
- Zeitnitz C
- Zeman M
- Zemla A
- Zengel K
- Zenin O
- Zenis T
- Zerwas D
- Zhang D
- Zhang F
- Zhang J
- Zhang L
- Zhang R
- Zhang X
- Zhang Z
- Zhao X
- Zhao Y
- Zhao Z
- Zhemchugov A
- Zhong J
- Zhou B
- Zhou C
- Zhou L
- Zhou L
- Zhou N
- Zhu CG
- Zhu H
- Zhu J
- Zhu Y
- Zhuang X
- Zhukov K
- Zibell A
- Zieminska D
- Zimine NI
- Zimmermann C
- Zimmermann R
- Zimmermann S
- Zinonos Z
- Zinser M
- Ziolkowski M
- Zivkovic L
- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √s=8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT>120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between EmissT>150 GeV and EmissT>700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presented
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at root s = 8 TeV with the ATLAS detector (vol 75, 299, 2015)
- Author
- Aad G
- Abbott B
- Abdallah J
- Abdinov O
- Aben R
- Abi B
- Abolins M
- AbouZeid OS
- Abramowicz H
- Abreu H
- Abreu R
- Abulaiti Y
- Acharya BS
- Adam ER
- Adamczyk L
- Adams DL
- Adelman J
- Adomeit S
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- Aguilar-Saavedra JA
- Agustoni M
- Ahlen SP
- Ahmadov F
- Aielli G
- Akerstedt H
- Akesson TPA
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- Akimov AV
- Alberghi GL
- Albert J
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- Alconada Verzini MJ
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- Chalupkova I
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- Chapman JD
- Charfeddine D
- Charlton DG
- Chau CC
- Cheatham S
- Chegwidden A
- Chekanov S
- Chekulaev SV
- Chelkov GA
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- Yen AL
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- Yorita K
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- Yoshihara K
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- Youssef S
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- Zaidan R
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- Zaman A
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- Zhemchugov A
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- Zobernig G
- Zoccoli A
- zur Nedden M
- Zurzolo G
- Zwalinski L
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.
- Author
- Ab Majid MA
- Ab Rahman AS
- Ab Rahman R
- Abayasinghe C
- Abbott T
- Abdullah NH
- Abdur-Rahman L
- Abeloos J
- Abernethy C
- Abidin UN
- Abrunhosa A
- Absar M
- Adam S
- Adams D
- Adams G
- Adamson M
- Adekola O
- Adelaja Y
- Ademola A
- Adenekan A
- Adenike O
- Adeolu AA
- Adetoye A
- Adewale B
- Adigun T
- Adolfsson A
- Aflori L
- Africander C
- Afshari A
- Agarwal V
- Agodirin O
- Aguero Vera M
- Aguzzoli C
- Ahmad A
- Ahmad N
- Ahmad T
- Ahmad T
- Ahmad Y
- Ahmed A
- Ahmed J
- Ai Y
- Aignatoaie M
- Aimoniotou-Georgiou E
- Akanmu O
- Akerman N
- Akinwale M
- Akring I
- Al 'Amri K
- Al Anizi M
- Al hussaini S
- Al-Soudaine Y
- Aladin H
- Alagbe-Briggs O
- Alaman Laguarda G
- Albaj S
- Alcock D
- Alcock L
- Aldecoa C
- Aldecoa C
- Aleixo FB
- Alexander H
- Alexander M
- Alexander-Sefre F
- Alherz F
- Ali H
- Ali M
- Ali S
- Alias A
- Alias AH
- Alias RLR
- Alit MA
- Allen S
- Allen SJ
- Allison J
- Alloj C
- Allorto NL
- Allsop J
- Almeida W
- Alonso E
- Alphonsus C
- Alvares D
- Alves MJ
- Amador JCB
- Ameer Y
- Amendola CP
- Ami N
- Amstrup-Hansen L
- Anagnou A
- Andersen C
- Anderson C
- Anderson C
- Anderson F
- Anderson P
- Andreadaki E
- Andreou A
- Andreou P
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- Angermair S
- Angus K
- Anillo V
- Antal O
- Antill P
- Antoniadou E
- Antonina W
- Apagaki E
- Apostolou K
- Applewhaite C
- Aquino LPG
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- Arawwawala D
- Ardern D
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- Arshad MA
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- Arustei M
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- Arya A
- Arya S
- Asimakos A
- Asudo F
- Athanasakis E
- Atiku M
- Attrill E
- Attwood C
- Auer P
- Avidan M
- Avila Sanchez FJ
- Avila EJD
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- Awad H
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- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2016
- Field of study
BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700
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