39 research outputs found
Addition of serum-containing medium to cerebrospinal fluid prevents cellular loss over time
Immediately after sampling, leukocyte counts in native cerebrospinal fluid (CSF) start to decrease rapidly. As the time lapse between CSF collection to analysis is not routinely registered, the clinical significance of decreasing cell counts in native CSF is not known. Earlier data suggest that addition of serum-containing medium to CSF directly after sampling prevents this rapid decrease in leukocyte counts and, thus, may improve the accuracy of CSF cell counting and cell characterization. Here, we prospectively examined the effect of storage time after lumbar puncture on counts of leukocytes and their major subsets in both native CSF and after immediate addition of serum-containing medium, measured by flow cytometry and microscopy. We collected CSF samples of 69 patients in tubes with and tubes without serum-containing medium and determined counts of leukocytes and subsets at 30Â minutes, 1 hour, and 5Â hours after sampling. Compared to cell counts at 30Â minutes, no significant decrease in cell number was observed in CSF with serum-containing medium 1 and 5Â hours after sampling, except for the granulocytes at 1Â hour. In native CSF, approximately 50% of leukocytes and all their subsets were lost after 1Â hour, both in flow cytometric and microscopic counting. In 6/7 (86%) samples with mild pleocytosis (5â15Â ĂÂ 106 leukocytes/l), native CSF at 1Â hour was incorrectly diagnosed as normocellular. In conclusion, addition of serum-containing medium to CSF directly after sampling prevents cell loss and allows longer preservation of CSF cells prior to analysis, both for microscopic and flow cytometric enumeration. We suggest that this protocol results in more accurate CSF cell counts and may prevent incorrect conclusions based on underestimated CSF cell counts
Addressing climate change with behavioral science: a global intervention tournament in 63 countries
Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventionsâ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behaviorâseveral interventions even reduced tree planting. Last, the effects of each intervention differed depending on peopleâs initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors
Addressing climate change with behavioral science:A global intervention tournament in 63 countries
Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p
Addressing climate change with behavioral science:A global intervention tournament in 63 countries
Addressing climate change with behavioral science:A global intervention tournament in 63 countries
Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions' effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior-several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people's initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.</p
The predictive ability of the 313 variantâbased polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
Abstract: Purpose: To evaluate the association between a previously published 313 variantâbased breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06â1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07â1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making
The predictive ability of the 313 variantâbased polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
PURPOSE : To evaluate the association between a previously published 313 variantâbased breast cancer (BC) polygenic risk score
(PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.
METHODS : We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402
prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2
(CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall
and ER-specific PRS313 and CBC risk.
RESULTS : For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard
ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06â1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive
PRS313, HR= 1.15, 95% CI (1.07â1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological
characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative
PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes,
respectively.
CONCLUSION : The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the
PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decisionmaking.This work was supported by the Alpe dâHuZes/Dutch Cancer Society (KWF
Kankerbestrijding) project 6253 and Dutch Cancer Society (KWF Kankerbestrijding)
project UL2014-7473. CIMBA: The CIMBA data management and data analysis were
supported by Cancer ResearchâUK grants C12292/A20861, C12292/A11174. G.C.T.
and A.B.S. are NHMRC Research Fellows. iCOGS: the European Communityâs Seventh
Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-
223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/
A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/
A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS
initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112âthe GAME-ON
initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes
of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-
87521), and the Ministry of Economic Development, Innovation and Export Trade
(PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research
Foundation, and the Ovarian Cancer Research Fund. OncoArray: the PERSPECTIVE
and PERSPECTIVE I&I projects funded by the Government of Canada through
Genome Canada and the Canadian Institutes of Health Research, the MinistĂšre de
lâĂconomie, de la Science et de lâInnovation du QuĂ©bec through Genome QuĂ©bec,
and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and
Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of
Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and
X01HG007492); and Cancer Research UK (C1287/A10118 and C1287/A16563). BCFR:
UM1 CA164920 from the National Cancer Institute. The content of this paper does
not necessarily reflect the views or policies of the National Cancer Institute or any of
the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does
mention of trade names, commercial products, or organizations imply endorsement
by the US Government or the BCFR. BFBOCC: Lithuania (BFBOCC-LT): Research
Council of Lithuania grant SEN-18/2015. BIDMC: Breast Cancer Research Foundation.
BMBSA: Cancer Association of South Africa (PI Elizabeth J. van Rensburg). BRI-COH: S.
L.N. is partially supported by the Morris and Horowitz Families Professorship. CNIO:
Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish
Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research
reported in this publication was supported by the National Cancer Institute of the
National Institutes of Health under grant number R25CA112486, and RC4CA153828
(PI: J. Weitzel) from the National Cancer Institute and the Office of the Director,
National Institutes of Health. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National Institutes of
Health. CONSIT TEAM: Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 number
16732) to P. Peterlongo. DEMOKRITOS: European Union (European Social FundâESF)
and Greek national funds through the Operational Program âEducation and Lifelong
Learningâ of the National Strategic Reference Framework (NSRF)âResearch Funding
Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA.
Investing in knowledge society through the European Social Fund. DFKZ: German
Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and
C1287/A11990. D.G.E. and F.L. are supported by an NIHR grant to the Biomedical
Research Centre, Manchester. The Investigators at The Institute of Cancer Research
and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the
Biomedical Research Centre at The Institute of Cancer Research and The Royal
Marsden NHS Foundation Trust. R.E. and E.B. are supported by Cancer Research UK
Grant C5047/A8385. R.E. is also supported by NIHR support to the Biomedical
Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: A.K.G. was in part funded by the NCI (R01 CA214545), The
University of Kansas Cancer Center Support Grant (P30 CA168524), The Kansas
Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority
Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical
Sciences Professorship. FPGMX: A. Vega is supported by the Spanish Health Research
Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds
through Research Activity Intensification Program (contract grant numbers: INT15/
00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica
en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018);
Autonomous Government of Galicia (Consolidation and structuring program:
IN607B), and by the Fundación Mutua Madrileña. The German Consortium for
Hereditary Breast and Ovarian Cancer (GC-HBOC) is funded by the German Cancer
Aid (110837, 70111850, coordinator: Rita K. Schmutzler, Cologne) and the Ministry for
Innovation, Science and Research of the State of North Rhine-Westphalia (#323-
8.0302.16.02-132142). GEMO: initially funded by the French National Institute of
Cancer (INCa, PHRC Ile de France, grant AOR 01 082, 2001-2003, grant 2013-1-BCB-01-
ICH-1), the Association âLe cancer du sein, parlons-en!â Award (2004), the Association
for International Cancer Research (2008-2010), and the Foundation ARC pour la
recherche sur le cancer (grant PJA 20151203365). It also received support from the
Canadian Institute of Health Research for the âCIHR Team in Familial Risks of Breast
Cancerâ program (2008â2013), and the European commission FP7, Project
«Collaborative Ovarian, breast and prostate Gene-environment Study (COGS),
Large-scale integrating project» (2009â2013). GEMO is currently supported by the
INCa grant SHS-E-SP 18-015. GEORGETOWN: The Survey, Recruitment, and Biospecimen
Collection Shared Resource at Georgetown University (NIH/NCI grant P30-
CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research,
and the Nina Hyde Center for Breast Cancer Research. G-FAST: Bruce Poppe is a
senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from
IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301
CIBERONC from ISCIII (Spain), partially supported by European Regional Development
FEDER funds. HEBCS: Helsinki University Hospital Research Fund, the Finnish Cancer
Society and the Sigrid Juselius Foundation. The HEBON study is supported by the
Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink
Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46
and the Transcan grant JTC 2012 Cancer 12-054. HRBCP: Hong Kong Sanatorium and
Hospital, Dr Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation,
National Institute of Health1R 03CA130065, and North California Cancer Center.
HUNBOCS: Hungarian Research Grants KTIA-OTKA CK-80745, NKFI_OTKA K-112228
and TUDFO/51757/2019-ITM. ICO: Contract grant sponsor: Supported by the Carlos III
National Health Institute funded by FEDER fundsâa way to build Europeâ(PI16/00563,
PI19/00553 and CIBERONC); the Government of Catalonia (Pla estratĂšgic de recerca i
innovaciĂł en salut (PERIS) Project MedPerCan, 2017SGR1282 and 2017SGR496); and
CERCA program.IHCC: supported by grant PBZ_KBN_122/P05/2004 and the program
of the Minister of Science and Higher Education under the name âRegional Initiative
of Excellenceâ in 2019â2022 project number 002/RID/2018/19 amount of financing 12
000 000 PLN. ILUH: Icelandic Association âWalking for Breast Cancer Researchâ and by
the Landspitali University Hospital Research Fund. INHERIT: Canadian Institutes of
Health Research for the âCIHR Team in Familial Risks of Breast Cancerâ programâgrant
CRN-87521 and the Ministry of Economic Development, Innovation and Export
Tradeâgrant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and â5Ă1000â Istituto
Oncologico Veneto grant. IPOBCS: Liga Portuguesa Contra o Cancro. kConFab: The
National Breast Cancer Foundation, and previously by the National Health and
Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer
Foundation of Western Australia. KOHBRA: the Korea Health Technology R&D Project
through the Korea Health Industry Development Institute (KHIDI), and the National
R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea
(HI16C1127; 1020350; 1420190). KUMC: NIGMS P20 GM130423 (to A.K.G.). MAYO: NIH
grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research
Excellence (SPORE) in Breast Cancer (CA116201), and a grant from the Breast Cancer
Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast
Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade.
Marc Tischkowitz is supported by the funded by the European Union Seventh
Framework Program (2007Y2013)/European Research Council (Grant No. 310018).
MODSQUAD: MH CZâDRO (MMCI, 00209805) and LM2018125, MEYSâNPS IâLO1413 to LF, and by Charles University in Prague project UNCE204024 (MZ). MSKCC: the
Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer
Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support
Grant/Core Grant (P30 CA008748). NAROD: 1R01 CA149429-01. NCI: the Intramural
Research Program of the US National Cancer Institute, NIH, and by support services
contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc,
Rockville, MD. NICCC: Clalit Health Services in Israel, the Israel Cancer Association and
the Breast Cancer Research Foundation (BCRF), NY. NNPIO: the Russian Foundation
for Basic Research (grants 17-00-00171, 18-515-45012 and 19-515-25001). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative
Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA
37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University
Comprehensive Cancer Center. PBCS: supported by the âFondazione Pisa per la
Scienza, project nr. 127/2016. Maria A Caligo was supported by the grant: ân. 127/16
Caratterizzazione delle varianti missenso nei geni BRCA1/2 per la valutazione del
rischio di tumore al senoâ by Fondazione Pisa, Pisa, Italy; SEABASS: Ministry of
Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/
06) and Cancer Research Initiatives Foundation. SMC: the Israeli Cancer Association.
SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of
Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996,
1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the
Entertainment Industry Fund National Womenâs Cancer Research Alliance and the
Breast Cancer research Foundation. O.I.O. is an ACS Clinical Research Professor. UCLA:
Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research
Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive
Cancer Center. UKFOCR: Cancer Research h UK. UPENN: Breast Cancer Research
Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for
BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency,
Cancer Australia, National Breast Cancer Foundation. WCP: B.Y.K. is funded by the
American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and
the National Center for Advancing Translational Sciences (NCATS), grant
UL1TR000124.https://www.gimjournal.org/am2023Genetic
Genomic investigations of unexplained acute hepatitis in children
Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children