9 research outputs found
Si detector macroscopic damage parameters during irradiation from measurements of dark current evolution with fluence
No full textEvolution of silicon microstrip detector currents during proton irradiation at the CERN PS
No full textPrototype ATLAS silicon microstrip detectors have been irradiated to the dose predicted for 10 years of LHC operation with protons at the CERN PS whilst cooled to the ATLAS design operating temperature. The detector currents were monitored during irradiation, which allows the predictions of bulk radiation damage parameterizations to be tested. Values for the damage constant α and the rate of acceptor creation β have been calculated and are in agreement with those previously published for the irradiation of silicon diodes
Global analysis of seagrass restoration: The importance of large-scale planting
No full textM.M. van Katwijk et al.In coastal and estuarine systems, foundation species like seagrasses, mangroves, saltmarshes or corals provide important ecosystem services. Seagrasses are globally declining and their reintroduction has been shown to restore ecosystem functions. However, seagrass restoration is often challenging, given the dynamic and stressful environment that seagrasses often grow in. From our world-wide meta-analysis of seagrass restoration trials (1786 trials), we describe general features and best practice for seagrass restoration. We confirm that removal of threats is important prior to replanting. Reduced water quality (mainly eutrophication), and construction activities led to poorer restoration success than, for instance, dredging, local direct impact and natural causes. Proximity to and recovery of donor beds were positively correlated with trial performance. Planting techniques can influence restoration success. The meta-analysis shows that both trial survival and seagrass population growth rate in trials that survived are positively affected by the number of plants or seeds initially transplanted. This relationship between restoration scale and restoration success was not related to trial characteristics of the initial restoration. The majority of the seagrass restoration trials have been very small, which may explain the low overall trial survival rate (i.e. estimated 37%). Successful regrowth of the foundation seagrass species appears to require crossing a minimum threshold of reintroduced individuals. Our study provides the first global field evidence for the requirement of a critical mass for recovery, which may also hold for other foundation species showing strong positive feedback to a dynamic environment. Synthesis and applications. For effective restoration of seagrass foundation species in its typically dynamic, stressful environment, introduction of large numbers is seen to be beneficial and probably serves two purposes. First, a large-scale planting increases trial survival - large numbers ensure the spread of risks, which is needed to overcome high natural variability. Secondly, a large-scale trial increases population growth rate by enhancing self-sustaining feedback, which is generally found in foundation species in stressful environments such as seagrass beds. Thus, by careful site selection and applying appropriate techniques, spreading of risks and enhancing self-sustaining feedback in concert increase success of seagrass restoration. For effective restoration of seagrass foundation species in its typically dynamic, stressful environment, introduction of large numbers is seen to be beneficial and probably serves two purposes. First, a large-scale planting increases trial survival - large numbers ensure the spread of risks, which is needed to overcome high natural variability. Secondly, a large-scale trial increases population growth rate by enhancing self-sustaining feedback, which is generally found in foundation species in stressful environments such as seagrass beds. Thus, by careful site selection and applying appropriate techniques, spreading of risks and enhancing self-sustaining feedback in concert increase success of seagrass restoration. Journal of Applied EcologyA.T. was funded by Greater Caribbean Energy and Environment Foundation grants. N.M. was supported by a Gledden Fellowship from the Institute of Advanced Studies of the University of Western Australia. N.M. C.M.D and A.C. were supported by Biomares contract number LIFE06 NAT/PT/000192. N.M. and C.M.D. were supported by Opera (FP7, contract number 308393). C.P. and the Cornell Cooperative Extension Marine Program are funded in part by County Executive Steve Bellone and the Suffolk County Legislature, Hauppauge, New York. E.B. and C.L. were funded by University of Pisa (Lardicci 308/ex60%2010). M.L.C and G.A.K were supported by ARC Linkage Grants (LP130100155, LP0454138)Peer Reviewe
Beer-derived (poly)phenol metabolism in individuals with and without metabolic Syndrome: A comparative dietary intervention
No full textThis article belongs to the Special Issue Advances in Phenolic Based Complexes.The data presented in this study are available under request from the corresponding author due to ethical reasons.The consumption of low-alcohol fermented beverages has been related to cardiovascular health improvements. Although the underlying mechanism is not completely understood, (poly)phenols have been proposed as one of the mediators. The objective of this study was to evaluate the impact of a controlled intervention with beer on (poly)phenols metabolism in individuals with and without metabolic syndrome (MetS). 20 participants (MetS and control) who consumed a standardized amount of beer during 6 weeks were recruited. Phenolic compounds were assessed in urine. Different changes in phenolic compounds associated with chronic beer consumption were found, particularly related to hesperetin conjugates and to the degradation of phenolic compounds derived from flavonoids and lignans. Noteworthily, MetS and control participants differed in baseline urine phenolic compound profiles and in their metabolization. Significant differences were found in the production and excretion of key (poly)phenols-derived metabolites, such as increased naringenin phase II conjugates in healthy subjects, or increased bacterial flavonoid catabolites. Certain relationships were observed between the phenolic compounds with metabolic and anthropometric variables. These findings suggest that beer-derived (poly)phenols are differentially metabolized according to metabolic-health status, and that they may contribute to certain metabolic health benefits through the modulation of specific metabolic pathways.This research was partly funded by a grant from “Foro para la Investigación de la Cerveza y Estilos de Vida (FICYE)” as well as by the “Network of Centers for Biomedical Research” (CIBER) of the Carlos III Health Institute (ISCIII) (CB06/03/0018), and research grants from the ISCIII (PI18/01160, PI21/01677) and co-financed by the Regional Development Fund (ERDF). Moreover, D.H.-N. was supported by a Sara Borrell postdoctoral contract (CD23/00111) from ISCIII-Madrid (Spain). C.M.D.-P. is supported by a postdoctoral Río Hortega (CM23/00128) from ISCIII-Madrid (Spain). M.J.G.-L. was funded by the Agencia Estatal de Investigación (PTA2022-021854-I). A.S.-V. was supported by a predoctoral PFIS (FI22/00193) from ISCIII-Madrid (Spain). I.M.-I. is supported by the “Miguel Servet Type II” program (CPII21/00013) under ISCIII-Madrid (Spain).Peer reviewe
Low microzooplankton grazing rates in the Arctic Ocean during a Phaeocystis pouchetii bloom (Summer 2007): fact or artifact of the dilution technique?
No full text15 pages, 7 figures, 4 tables.-- This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Plankton Research following peer review. The definitive publisher-authenticated version Journal of Plankton Research 33 (5): 687-701 (2011)is available online at: https://doi.org/10.1093/plankt/fbq142We studied the structure and dynamics of the microbial community of Arctic waters during July 2007 using a microzooplankton grazing dilution approach. The sampling covered a latitudinal transect along the East Greenland Sea, and a series of stations in the high Arctic (up to 808500N), west and north of the Svalbard Islands. A main feature of the area was the presence of Phaeocystis pouchetii, which formed dense blooms. Despite the considerable biomass of microzooplankton
(mostly large ciliates and dinoflagellates), their grazing impact on phytoplankton, assessed as total chlorophyll a, was significant in only 6 out of 16 experiments, which resulted in 8% of the standing stock being consumed on average. Overall, phytoplankton instantaneous growth rates were very low and even negative at times (range: 20.24 to 0.14; average: 20.04 for total chlorophyll), which could not be attributed to nutrient limitation nor the estimated microzooplankton grazing. We
present three non-exclusive explanations for this fact: (i) we were facing a senescent community in which many organisms were dying either as a result of virus infections or for other natural causes, as corroborated by parallel estimates of natural cell mortality using membrane permeability probes; (ii) the widespread and abundant P. pouchetii was probably deterring grazing and adversely affecting the entire planktonic community at the time of the study; and (iii) the dilution technique
failed to give a real estimate of grazing (i.e. either non- significant or positive slopes), likely as a consequence of trophic cascades (decline of major grazers in the more concentrated treatments) combined with saturated-feeding responses. This last point calls for special attention when intending to use the dilution technique in productive environments, where grazing may be saturatedThis research was supported by the Spanish grants POL2006-0550/CTM to C.M.D. CTM2009-08783 to A.C., CTM2006-12344-C02-01 to M.A., CTM2007-60052 to E.S. and grant 2005SGR-00219 from the Generalitat de Catalunya to the research group, and a PhD fellowship, BES-2005-7491 to R.A.Peer reviewe
Negative Symptoms in Early-Onset Psychosis and Their Association With Antipsychotic Treatment Failure.
No full textThis is the author accepted manuscript. The final version is available from OUP via the DOI in this recordThe prevalence of negative symptoms (NS) at first episode of early-onset psychosis (EOP), and their effect on psychosis prognosis is unclear. In a sample of 638 children with EOP (aged 10-17 y, 51% male), we assessed (1) the prevalence of NS at first presentation to mental health services and (2) whether NS predicted eventual development of multiple treatment failure (MTF) prior to the age of 18 (defined by initiation of a third trial of novel antipsychotic due to prior insufficient response, intolerable adverse-effects or non-adherence). Data were extracted from the electronic health records held by child inpatient and community-based services in South London, United Kingdom. Natural Language Processing tools were used to measure the presence of Marder Factor NS and antipsychotic use. The association between presenting with ≥2 NS and the development of MTF over a 5-year period was modeled using Cox regression. Out of the 638 children, 37.5% showed ≥2 NS at first presentation, and 124 (19.3%) developed MTF prior to the age of 18. The presence of NS at first episode was significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07-2.46; P = .02) after controlling for a number of potential confounders including psychosis diagnostic classification, positive symptoms, comorbid depression, and family history of psychosis. Other factors associated with MTF included comorbid autism spectrum disorder, older age at first presentation, Black ethnicity, and family history of psychosis. In EOP, NS at first episode are prevalent and may help identify a subset of children at higher risk of responding poorly to antipsychotics.J.D. received supported by a Medical Research Council (MRC) Clinical Research Training Fellowship (MR/L017105/1) and Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. H.D. and S.L. have received salary support from the Foundation of Professional Services to Adolescents, UK. R.D.H. was funded by an MRC Fellowship (MR/J01219X/1). R.P. was funded by an MRC CRTF (MR/K002813/1). C.A., L.P-C., and C.M.D-C. have held grants from the Spanish Ministry of Economy, Industry and Competitiveness. Instituto de Salud Carlos III, co-financed by ERDF Funds from the European Commission, “A way of making Europe,” CIBERSAM, Madrid Regional Government (S2010/BMD-2422 AGES), European Union Structural Funds and European Union Seventh Framework Program under grant agreements FP7-HEALTH-2009-2.2.1-2-241909 (EU-GEI), FP7-HEALTH-2009-2.2.1-3-242114 (OPTiMISE), FP7-HEALTH-2013-2.2.1-2-603196 (PSYSCAN)and FP7- HEALTH-2013-2.2.1-2-602478 (METSY); European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement No-115916; PRISM); Fundación Alicia Koplowitz and Fundación Mutua Madrileña. M.H., J.H.M. and H.S. receive salary support from the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health
Microresonators for organic semiconductor and fluidic lasers
No full textThis thesis describes a number of studies of microstructured optical resonators,
designed with the aim of enhancing the performance of organic semiconductor lasers
and exploring potential applications. The methodology involves the micro-engineering
of the photonic environment in order to modify the pathways of the emitted light and
control the feedback mechanism. The research focuses on designing new organic
microstructures using established semi-analytical and numerical methods, developing fabrication techniques using electron-beam lithography, and optically characterising the resulting structures.
Control of the feedback mechanism in conjugated polymer lasers is first investigated by studying Distributed Feedback or photonic crystal resonators based on a square feedback lattice. This study identified the diffraction to free space radiation as a major source of loss in current microstructured resonator designs. By cancelling the coupling to free space through the use of different feedback symmetries and diffraction orders, a threshold reduction by almost an order of magnitude is demonstrated.
The introduction of mid-gap defect photonic states in an otherwise uniformly periodic
structure was studied in Distributed Bragg Reflector (DBR) resonators. This enabled
GaN diode pumped polymer lasers to be demonstrated, indicating that the transition
from complex excitation sources to more compact systems is possible. Devices for
potential applications in the field of optical communications are also explored by
demonstrating a polymer DBR laser based on silicon. In this way, the potential for
integrating conjugated polymers with silicon photonics is confirmed.
Photonic crystal fibres, which have a periodic microstructure in the transverse
direction, are explored as an alternative means for controlling the optical properties of organic lasers. Fluidic fibre organic lasers were demonstrated as efficient sources with good spectral purity. In these devices, mechanisms to tune the emission wavelength
were explored and the origin of the frequency selection mechanism was investigated.The author received a Wingate Scholarship for the Si experiments
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
No full textLeft-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples-and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant
associations. Assessment of age-and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered
left-hemisphere language network organization in schizophreniaAcknowledgments. The ENIGMA project is in part supported by the National
Institute of Biomedical Imaging and Bioengineering of the NIH (U54EB020403).
The content is solely the responsibility of the authors and does not necessarily
represent the official views of the NIH. Individual Funding Sources: D.S., M.C.P.,
S.E.F., and C.F.: Max Planck Society (Germany). R.A.-A.: Miguel Servet contract
from the Carlos III Health Institute (CP18/00003). J.V.-B.: Instituto de Investigación
Sanitaria Valdecilla (IDIVAL) (INT/A21/10, INT/A20/04). D.A.: South-Eastern Norway
Regional Health Authority (2019107, 2020086). L.T.W.: Research Council of
Norway (223273, 300767), South-Eastern Norway Regional Health Authority
(2019101), and European Research Council under the European Union’s Horizon
2020 Research and Innovation Program (ERC StG, 802998). O.A.A.: Research
Council of Norway (223273, 275054), KG Jebsen Stiftelsen, South East
Norway Health Authority (2017-112, 2019-108). P.K.: NIH (R01MH123163,
R01EB015611). M.J.G.: National Health and Medical Research Council (NHMRC)
(630471, 1051672, 1081603). C.P.: NHMRC Senior Principal Research Fellowship
(1105825), NHMRC L3 Investigator Grant (1196508). V.D.C.: NIH (R01MH118695),
NSF (2112455). J.M.F.: Senior Research Career Scientist Award, Department of
Veterans Affairs. P.F.-C.: Centro de Investigación Biomédica en Red de Salud
Mental (CIBERSAM) and Instituto de Salud Carlos III, cofunded by European Union
(European Regional Development Fund (ERDF)/European Social Fund (ESF),
“Investing in your future”): Sara Borrell Research contract (CD19/00149). G.S.:
Italian Ministry of Health (RC17-18-19-20-21/A). A.N.V.: National Institute of
Mental Health (NIMH), Canadian Institutes of Health Research (CIHR), Canada
Foundation for Innovation, Centre for Addiction and Mental Health (CAMH)
Foundation, University of Toronto. Y.-C.C.: Korean Mental Health Technology R&D
Project (HL19C0015) and Korea Health Technology R&D Project through the Korea
Health Industry Development Institute (HI18C2383), funded by the Ministry of
Health & Welfare, Republic of Korea. J.M.S.: NIH (1P20RR021938-01). A.R.M.:
NIH (P30GM122734, R01MH101512). C.M.D.-C.: Instituto de Salud Carlos III,
Spanish Ministry of Science and Innovation (PI17/00481, PI20/00721,
JR19/00024). S. Cervenka: Swedish Research Council (523-2014-3467). M.
Kirschner: Swiss National Science Foundation (SNSF) (P2SKP3_178175). T.H.:
CIHR (142255), Ministry of Health of the Czech Republic (16-32791A, NU20-
04-00393), Brain & Behavior Research Foundation (BBRF) Young and Independent
Investigator Awards. A. James: Medical Research Council (MRC) (G0500092).
P.H.: NARSAD grant from the BBRF (28445), Research Grant from the
Novartis Foundation (20A058). R.C.G.: NIH (1R01MH117014, 1R01MH119219).
N.J.: NIH (R01MH117601). S.E.M.: NHMRC (APP1172917). J.A.T.: NIH (R01MH1
21246). Dataset-Specific Funding Sources and Acknowledgments: AMC:
Supported by grants from The Netherlands Organisation for Health Research and
Development (ZonMw) (3160007, 91676084, 31160003, 31180002, 31000056,
2812412, 100001002, 100002034), the Dutch Research Council (NWO)
(90461193, 40007080, 48004004, 40003330), the Amsterdam Brain Imaging
Platform, Neuroscience Campus Amsterdam, and the Dutch Brain Foundation.
Processing with FreeSurfer was performed on the Dutch e-Science Grid through
BiG Grid project and COMMIT project “e-Biobanking with imaging for healthcare,”
which are funded by the NWO. ASRB: Australian Schizophrenia Research Bank,
supported by the NHMRC (Enabling Grant, 386500), the Pratt Foundation,
Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia
Research Institute. Chief Investigators for ASRB were S.V.C., P.T.M., B.J.M., U.S.,
R.J.S., V.J.C., F.A.H., C.P., Assen Jablensky. We thank C.M.L., the ASRB Manager,
and acknowledge the help of Jason Bridge for ASRB database queries. CAMH:
Datasets were collected and shared with support from the CAMH Foundation and
the CIHR. CASSI (Cognitive and Affective Symptoms in Schizophrenia Intervention):
Downloaded from https://www.pnas.org by UNIVERSIDAD DE CANTABRIA BIBLIOTECA UNIV/OFIC.PBL.PER. on April 10, 2023 from IP address 193.144.191.20.
Supported by the University of New South Wales School of Psychiatry, the NHMRC (568807), Neuroscience Research Australia, the Schizophrenia Research Institute
utilizing infrastructure funding from NSW Ministry of Health, the Macquarie
Group Foundation, and the ASRB (see above). CIAM (Cortical Inhibition and
Attentional Modulation): The CIAM group (PI: F.M.H.) was supported by the
University Research Committee, University of Cape Town; South African National
Research Foundation (NRF); South African Medical Research Council (SA MRC).
CLING (Clinical Neuroscience Goettingen): Sample data collection partially supported by the Deutsche Forschungsgemeinschaft (DFG) (GR1950/5-1 to O.G.).
COBRE (Center for Biomedical Research Excellence): Supported by NIH
(R01EB006841, P20GM103472, 5R01MH094524 to V.D.C. and J.A.T.
R01AA021771 and P50AA022534 to J.M.S.), and the NSF (1539067).
EdinburghEHRS: Funded by the MRC (G9226254, G9825423), the Dr. Mortimer
and Theresa Sackler Foundation. EdinburghFunc: Funded by the MRC Clinical
Training Fellowship (G84/5699) and Health Foundation Clinician Scientist
Fellowship (2268/4295). EdinburghSFMH: Funded by an award from the
Translational Medicine Research Collaboration (NS_EU_166), Scottish Enterprise,
Pfizer, the Dr. Mortimer and Theresa Sackler Foundation. The University of
Edinburgh is a charitable body, registered in Scotland, with registration number
SC005336. Is e buidheann carthannais a th’ ann an Oilthigh Dhùn Èideann,
clàraichte an Alba, àireamh clàraidh SC005336. EONCKS: Supported by the SA
MRC and the New Partnership for Africa’s Development initiative through the
Department of Science and Technology of South Africa (#65174). ESO: Supported
by the Ministry of Health of the Czech Republic (NU20-04-00393). FBIRN
(Function Biomedical Informatics Research Network): Supported by the National
Center for Research Resources at the NIH (1 U24 RR021992 (FBIRN) and 1 U24
RR025736-01 (Biomedical Informatics Research Network Coordinating Center;
http://www.birncommunity.org)). Data were processed by the UCI HighPerformance Computing cluster supported by Joseph Farran (supported by NIMH
R01 MH-58262), Harry Mangalam, and Adam Brenner (supported by NIH 5R01
MH61603, 2R01MH058251), and the National Center for Research Resources
and the National Center for Advancing Translational Sciences, NIH (through grant
UL1 TR000153). FBIRN thank Mrs. Liv McMillan for overall study coordination.
FOR2107 Marburg: Funded by the DFG, T.T.J.K. (speaker FOR2107; KI588/14-1,
KI588/14-2), Axel Krug (KR3822/5-1, KR3822/7-2), I.N. (NE2254/1-2, NE2254/3-1,
NE2254/4-1), Carsten Konrad (KO4291/3-1), and A. Jansen (JA1890/7-1,
JA1890/7-2). FOR2107 Münster: Funded by the DFG (FOR2107 DA1151/5-1,
DA1151/5-2 to U.D.; SFB-TRR58, Projects C09 and Z02 to U.D.) and the
Interdisciplinary Center for Clinical Research of the medical faculty of Münster
(Dan3/012/17 to U.D.). Frankfurt: MRI was performed at the Frankfurt Brain
Imaging Centre, supported by the DFG and the German Ministry for Education
and Research (Brain Imaging Center Frankfurt/Main, DLR01GO0203). GAP
(Genetics and Psychosis): The GAP dataset represents independent research
funded by the National Institute for Health and Care Research (NIHR) Biomedical
Research Centre at South London, Maudsley National Health Service (NHS)
Foundation Trust, and King’s College London. The views expressed are those of
the author(s) and not necessarily those of the NHS, the NIHR, or the Department
of Health. GIPSI: Supported by “PRISMA U.T” Colciencias Invitación 990 del 3 de
Agosto de 2017, Código 111577757629, Contrato 781 de 2017. GROUP: We
thank Truda Driesen and Inge Crolla for their coordinating roles in the data collection, as well as the G.R.O.U.P. investigators: R.S.K., Don H. Linszen, Jim van Os,
Durk Wiersma, Richard Bruggeman, W.C., L.dH., Lydia Krabbendam, Inez MyinGermeys. Infrastructure for the GROUP study is funded through the Geestkracht
programme of ZonMw (10-000-1001), and matching funds from participating
pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and
universities and mental health care organizations (Amsterdam: Academic
Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical
Centre, GGZ Noord Holland Noord; Groningen: University Medical Center
Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe,
Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psychomedical center, The Hague; Maastricht: Maastricht University Medical Centre and
the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent
van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland
GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of
Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt,
OPZ Rekem; Utrecht: University Medical Center Utrecht and the mental health
institutions Altrecht, GGZ Centraal, and Delta). HMS (Homburg Multidiagnosis Study): Sample data collection was supported by a grant of the Competence
Network Schizophrenia to O.G.. HUBIN (Human Brain Informatics): Supported by
the Swedish Research Council (K2015-62X-15077-12-3), 2017-00949, the
regional agreement on medical training and clinical research between Stockholm
County Council and the Karolinska Institutet, the Knut and Alice Wallenberg
Foundation. Huilong: Funded by the National Natural Science Foundation of
China (81761128021; 31671145; 81401115; 81401133), Beijing Municipal
Science & Technology Commission grant (Z141107002514016), Beijing Natural
Science Foundation (7162087), Beijing Municipal Administration of Hospitals
Clinical medicine Development of special funding (XMLX201609; zylx201409).
IGP: Imaging Genetics in Psychosis study, funded by Project Grants from the
NHMRC (APP630471 and APP1081603), and the Macquarie University’s ARC
Centre of Excellence in Cognition and its Disorders (CE110001021). This project
used participants from the ASRB (see above), using an infrastructure grant from
the NSW Ministry of Health. IMH: Supported by research grants from the National
Healthcare Group, Singapore (SIG/05004; SIG/05028), and the Singapore
Bioimaging Consortium (RP C009/2006) awarded to K.S. KaSP: Supported by
the Swedish Research Council (K2015-62X-15077-12-3), and by grants from the
Swedish Medical Research Council (2009-7053, 2013-2838, 523-2014-3467),
the Swedish Brain Foundation, Åhlén-siftelsen, Svenska Läkaresällskapet, Petrus
och Augusta Hedlunds Stiftelse, Torsten Söderbergs Stiftelse, the AstraZenecaKarolinska Institutet Joint Research Program in Translational Science, Söderbergs
Königska Stiftelse, Professor Bror Gadelius Minne, Knut och Alice Wallenbergs
stiftelse, the Swedish Federal Government under the LUA/ALF agreement (C.M.S.,
S. Cervenka), Centre for Psychiatry Research, KID-funding from the Karolinska
Institutet. Madrid: Supported by the Spanish Ministry of Science and Innovation,
Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), cofinanced
by ERDF Funds from the European Commission, “A way of making Europe,”
CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2),
European Union Structural Funds, European Union Seventh Framework Program
(FP7-4-HEALTH-2009-2.2.1-2-241909—Project EU-GEI, FP7-HEALTH-2013-2.2.1-
2-603196—Project PSYSCAN, and FP7-HEALTH-2013-2.2.1-2-602478—Project
METSY), European Union H2020 Program under the Innovative Medicines
Initiative 2 Joint Undertaking (115916—Project PRISM, and 777394—Project
AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz. MCIC:
Supported by the NIH (NIH/NCRR P41RR14075, R01EB005846 to V.D.C.), the
Department of Energy (DE-FG02- 99ER62764), the Mind Research Network, the
Morphometry BIRN (1U24, RR021382A), the Function BIRN (U24RR021992-01,
NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to V.D.C.), the DFG
(research fellowship to S.E.), and a NARSAD Young Investigator Award (to S.E.).
MPRC: Support received from NIH (U01MH108148, 2R01EB015611,
R01MH112180, R01DA027680, R01MH085646, P50MH103222, and
T32MH067533), a State of Maryland contract (M00B6400091), and NSF grant
(1620457). OLIN: Supported by NIH (R01MH106324, R01MH077945). Osaka:
Partially supported by AMED (JP21dm0307002, JP21dm0207069,
JP21dk0307103, JP21uk1024002, and JP21wm0425012), JSPS KAKENHI
(JP20H03611, JP20K06920), and Intramural Research Grant (3-1) for
Neurological and Psychiatric Disorders of NCNP. Computations were performed
using Research Center for Computational Science, Okazaki, Japan. Oxford: We
would like to thank the participants and their families, referring psychiatrists, and
the Donnington Health Centre, Oxford. This study is supported by the MRC,
OHSRC, UK EPSRC, BBSRC, and Wellcome Trust. PAFIP: We wish to thank all PAFIP
research teams and all patients and family members who participated in the
study. PAFIP has been funded by Instituto de Salud Carlos III through the projects
PI14/00639, PI14/00918, and PI17/01056 (cofunded by ERDF/ESF “Investing in
your future”), Health Research Institute Marques de Valdecilla (NTC0235832,
NCT02534363), Instituto de Salud Carlos III, FIS 00/3095, 01/3129, PI020499,
PI060507, PI10/00183, the SENY Fundació Research Grant (CI 2005‐0308007),
the Fundación Marqués de Valdecilla (API07/011), MINECOSAF2013-46292-R,
PSYSCAN (Exp.: HEALTH.2013.2.2.1-2_Grant agreement no. 603196). We
want to particularly acknowledge the patients and the BioBankValdecilla
(PT13/0010/0024) integrated in the Spanish National Biobanks Network for its
collaboration. We thank IDIVAL Neuroimaging Unit for its help in the technical
execution of this work. RSCZ: Supported in part by the RFBR (20-013-00748).
SCORE: This study was supported in part by the SNSF (3232BO_119382). We
thank the FePsy (Frueherkennung von Psychosen; early detection of psychosis)
Downloaded from https://www.pnas.org by UNIVERSIDAD DE CANTABRIA BIBLIOTECA UNIV/OFIC.PBL.PER. on April 10, 2023 from IP address 193.144.191.20.
Study Group from the University of Basel, Department of Psychiatry, Switzerland, for the recruitment of the study participants. The FePsy Study was supported in part
by grant no. SNF 3200-057216/1, ext./2, ext./3. SNUH: Supported by the Basic
Science Research Program through the National Research Foundation of Korea (NRF)
and the Korea Brain Research Institute (KBRI) basic research program through the
KBRI, funded by the Ministry of Science, ICT & Future Planning (2019R1C1C1002457,
2020M3E5D9079910, 21-BR-03–01). SWIFT: Supported in part by the SNSF
(320030_146789). TOP: Supported by the Research Council of Norway (#160181,
190311, 223273, 213837, 249711), the South-East Norway Health Authority
(2014114, 2014097, 2017- 112), the Kristian Gerhard Jebsen Stiftelsen (SKGJ‐
MED‐008), and the European Community’s Seventh Framework Programme
(FP7/2007–2013), grant agreement no. 602450 (IMAGEMEND). UCISZ: Supported
by the NIMH (R21MH097196 to T.G.M.v.E.). Data were processed by the UCI HighPerformance Computing cluster (see FBIRN). UMCU: Supported by ZonMw
(90802123, 91746370 to H.E.H.P., and 10-000-1001 to R.S.K.). UNIBA: Supported
by grant funding from the Italian Ministry of Research (2017M7SZM8_004, PI A.B.;
2017K2NEF4, PI G.P.). UNIMAAS: Supported by ZonMw (91112002) and by a personal grant to T.v.A. (ZonMw-VIDI: 91712394). This clinical trial was registered in
the Dutch clinical trial registry under ID: NTR5094 (https://trialsearch.who.int/Trial2.
aspx?TrialID=NTR5094). Zurich: Funded by the SNSF
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
No full textENIGMA consortium: et al.Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.The ENIGMA project is in part supported by the National Institute of Biomedical Imaging and Bioengineering of the NIH (U54EB020403). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Individual Funding Sources: D.S., M.C.P., S.E.F., and C.F.: Max Planck Society (Germany). R.A.-A.: Miguel Servet contract from the Carlos III Health Institute (CP18/00003). J.V.-B.: Instituto de Investigación Sanitaria Valdecilla (IDIVAL) (INT/A21/10, INT/A20/04). D.A.: South-Eastern Norway Regional Health Authority (2019107, 2020086). L.T.W.: Research Council of Norway (223273, 300767), South-Eastern Norway Regional Health Authority (2019101), and European Research Council under the European Union’s Horizon 2020 Research and Innovation Program (ERC StG, 802998). O.A.A.: Research Council of Norway (223273, 275054), KG Jebsen Stiftelsen, South East Norway Health Authority (2017-112, 2019-108). P.K.: NIH (R01MH123163, R01EB015611). M.J.G.: National Health and Medical Research Council (NHMRC) (630471, 1051672, 1081603). C.P.: NHMRC Senior Principal Research Fellowship (1105825), NHMRC L3 Investigator Grant (1196508). V.D.C.: NIH (R01MH118695), NSF (2112455). J.M.F.: Senior Research Career Scientist Award, Department of Veterans Affairs. P.F.-C.: Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM) and Instituto de Salud Carlos III, cofunded by European Union (European Regional Development Fund (ERDF)/European Social Fund (ESF), “Investing in your future”): Sara Borrell Research contract (CD19/00149). G.S.: Italian Ministry of Health (RC17-18-19-20-21/A). A.N.V.: National Institute of Mental Health (NIMH), Canadian Institutes of Health Research (CIHR), Canada Foundation for Innovation, Centre for Addiction and Mental Health (CAMH) Foundation, University of Toronto. Y.-C.C.: Korean Mental Health Technology R&D Project (HL19C0015) and Korea Health Technology R&D Project through the Korea Health Industry Development Institute (HI18C2383), funded by the Ministry of Health & Welfare, Republic of Korea. J.M.S.: NIH (1P20RR021938-01). A.R.M.: NIH (P30GM122734, R01MH101512). C.M.D.-C.: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI17/00481, PI20/00721, JR19/00024). S. Cervenka: Swedish Research Council (523-2014-3467). M. Kirschner: Swiss National Science Foundation (SNSF) (P2SKP3_178175). T.H.: CIHR (142255), Ministry of Health of the Czech Republic (16-32791A, NU20-04-00393), Brain & Behavior Research Foundation (BBRF) Young and Independent Investigator Awards. A. James: Medical Research Council (MRC) (G0500092). P.H.: NARSAD grant from the BBRF (28445), Research Grant from the Novartis Foundation (20A058). R.C.G.: NIH (1R01MH117014, 1R01MH119219). N.J.: NIH (R01MH117601). S.E.M.: NHMRC (APP1172917). J.A.T.: NIH (R01MH121246). Dataset-Specific Funding Sources and Acknowledgments: AMC: Supported by grants from The Netherlands Organisation for Health Research and Development (ZonMw) (3160007, 91676084, 31160003, 31180002, 31000056, 2812412, 100001002, 100002034), the Dutch Research Council (NWO) (90461193, 40007080, 48004004, 40003330), the Amsterdam Brain Imaging Platform, Neuroscience Campus Amsterdam, and the Dutch Brain Foundation. Processing with FreeSurfer was performed on the Dutch e-Science Grid through BiG Grid project and COMMIT project “e-Biobanking with imaging for healthcare,” which are funded by the NWO. ASRB: Australian Schizophrenia Research Bank, supported by the NHMRC (Enabling Grant, 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief Investigators for ASRB were S.V.C., P.T.M., B.J.M., U.S., R.J.S., V.J.C., F.A.H., C.P., Assen Jablensky. We thank C.M.L., the ASRB Manager, and acknowledge the help of Jason Bridge for ASRB database queries. CAMH: Datasets were collected and shared with support from the CAMH Foundation and the CIHR. CASSI (Cognitive and Affective Symptoms in Schizophrenia Intervention): Supported by the University of New South Wales School of Psychiatry, the NHMRC (568807), Neuroscience Research Australia, the Schizophrenia Research Institute utilizing infrastructure funding from NSW Ministry of Health, the Macquarie Group Foundation, and the ASRB (see above). CIAM (Cortical Inhibition and Attentional Modulation): The CIAM group (PI: F.M.H.) was supported by the University Research Committee, University of Cape Town; South African National Research Foundation (NRF); South African Medical Research Council (SA MRC). CLING (Clinical Neuroscience Goettingen): Sample data collection partially supported by the Deutsche Forschungsgemeinschaft (DFG) (GR1950/5-1 to O.G.). COBRE (Center for Biomedical Research Excellence): Supported by NIH (R01EB006841, P20GM103472, 5R01MH094524 to V.D.C. and J.A.T. R01AA021771 and P50AA022534 to J.M.S.), and the NSF (1539067). EdinburghEHRS: Funded by the MRC (G9226254, G9825423), the Dr. Mortimer and Theresa Sackler Foundation. EdinburghFunc: Funded by the MRC Clinical Training Fellowship (G84/5699) and Health Foundation Clinician Scientist Fellowship (2268/4295). EdinburghSFMH: Funded by an award from the Translational Medicine Research Collaboration (NS_EU_166), Scottish Enterprise, Pfizer, the Dr. Mortimer and Theresa Sackler Foundation. The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. Is e buidheann carthannais a th’ ann an Oilthigh Dhùn Èideann, clàraichte an Alba, àireamh clàraidh SC005336. EONCKS: Supported by the SA MRC and the New Partnership for Africa’s Development initiative through the Department of Science and Technology of South Africa (#65174). ESO: Supported by the Ministry of Health of the Czech Republic (NU20-04-00393). FBIRN (Function Biomedical Informatics Research Network): Supported by the National Center for Research Resources at the NIH (1 U24 RR021992 (FBIRN) and 1 U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org)). Data were processed by the UCI High-Performance Computing cluster supported by Joseph Farran (supported by NIMH R01 MH-58262), Harry Mangalam, and Adam Brenner (supported by NIH 5R01 MH61603, 2R01MH058251), and the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH (through grant UL1 TR000153). FBIRN thank Mrs. Liv McMillan for overall study coordination. FOR2107 Marburg: Funded by the DFG, T.T.J.K. (speaker FOR2107; KI588/14-1, KI588/14-2), Axel Krug (KR3822/5-1, KR3822/7-2), I.N. (NE2254/1-2, NE2254/3-1, NE2254/4-1), Carsten Konrad (KO4291/3-1), and A. Jansen (JA1890/7-1, JA1890/7-2). FOR2107 Münster: Funded by the DFG (FOR2107 DA1151/5-1, DA1151/5-2 to U.D.; SFB-TRR58, Projects C09 and Z02 to U.D.) and the Interdisciplinary Center for Clinical Research of the medical faculty of Münster (Dan3/012/17 to U.D.). Frankfurt: MRI was performed at the Frankfurt Brain Imaging Centre, supported by the DFG and the German Ministry for Education and Research (Brain Imaging Center Frankfurt/Main, DLR01GO0203). GAP (Genetics and Psychosis): The GAP dataset represents independent research funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London, Maudsley National Health Service (NHS) Foundation Trust, and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. GIPSI: Supported by “PRISMA U.T” Colciencias Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017. GROUP: We thank Truda Driesen and Inge Crolla for their coordinating roles in the data collection, as well as the G.R.O.U.P. investigators: R.S.K., Don H. Linszen, Jim van Os, Durk Wiersma, Richard Bruggeman, W.C., L.dH., Lydia Krabbendam, Inez Myin-Germeys. Infrastructure for the GROUP study is funded through the Geestkracht programme of ZonMw (10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord; Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical center, The Hague; Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem; Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal, and Delta). HMS (Homburg Multidiagnosis Study): Sample data collection was supported by a grant of the Competence Network Schizophrenia to O.G. HUBIN (Human Brain Informatics): Supported by the Swedish Research Council (K2015-62X-15077-12-3), 2017-00949, the regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet, the Knut and Alice Wallenberg Foundation. Huilong: Funded by the National Natural Science Foundation of China (81761128021; 31671145; 81401115; 81401133), Beijing Municipal Science & Technology Commission grant (Z141107002514016), Beijing Natural Science Foundation (7162087), Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding (XMLX201609; zylx201409). IGP: Imaging Genetics in Psychosis study, funded by Project Grants from the NHMRC (APP630471 and APP1081603), and the Macquarie University’s ARC Centre of Excellence in Cognition and its Disorders (CE110001021). This project used participants from the ASRB (see above), using an infrastructure grant from the NSW Ministry of Health. IMH: Supported by research grants from the National Healthcare Group, Singapore (SIG/05004; SIG/05028), and the Singapore Bioimaging Consortium (RP C009/2006) awarded to K.S. KaSP: Supported by the Swedish Research Council (K2015-62X-15077-12-3), and by grants from the Swedish Medical Research Council (2009-7053, 2013-2838, 523-2014-3467), the Swedish Brain Foundation, Åhlén-siftelsen, Svenska Läkaresällskapet, Petrus och Augusta Hedlunds Stiftelse, Torsten Söderbergs Stiftelse, the AstraZeneca-Karolinska Institutet Joint Research Program in Translational Science, Söderbergs Königska Stiftelse, Professor Bror Gadelius Minne, Knut och Alice Wallenbergs stiftelse, the Swedish Federal Government under the LUA/ALF agreement (C.M.S., S. Cervenka), Centre for Psychiatry Research, KID-funding from the Karolinska Institutet. Madrid: Supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), cofinanced by ERDF Funds from the European Commission, “A way of making Europe,” CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds, European Union Seventh Framework Program (FP7-4-HEALTH-2009-2.2.1-2-241909—Project EU-GEI, FP7-HEALTH-2013-2.2.1-2-603196—Project PSYSCAN, and FP7-HEALTH-2013-2.2.1-2-602478—Project METSY), European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (115916—Project PRISM, and 777394—Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz. MCIC: Supported by the NIH (NIH/NCRR P41RR14075, R01EB005846 to V.D.C.), the Department of Energy (DE-FG02- 99ER62764), the Mind Research Network, the Morphometry BIRN (1U24, RR021382A), the Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to V.D.C.), the DFG (research fellowship to S.E.), and a NARSAD Young Investigator Award (to S.E.). MPRC: Support received from NIH (U01MH108148, 2R01EB015611, R01MH112180, R01DA027680, R01MH085646, P50MH103222, and T32MH067533), a State of Maryland contract (M00B6400091), and NSF grant (1620457). OLIN: Supported by NIH (R01MH106324, R01MH077945). Osaka: Partially supported by AMED (JP21dm0307002, JP21dm0207069, JP21dk0307103, JP21uk1024002, and JP21wm0425012), JSPS KAKENHI (JP20H03611, JP20K06920), and Intramural Research Grant (3-1) for Neurological and Psychiatric Disorders of NCNP. Computations were performed using Research Center for Computational Science, Okazaki, Japan. Oxford: We would like to thank the participants and their families, referring psychiatrists, and the Donnington Health Centre, Oxford. This study is supported by the MRC, OHSRC, UK EPSRC, BBSRC, and Wellcome Trust. PAFIP: We wish to thank all PAFIP research teams and all patients and family members who participated in the study. PAFIP has been funded by Instituto de Salud Carlos III through the projects PI14/00639, PI14/00918, and PI17/01056 (cofunded by ERDF/ESF “Investing in your future”), Health Research Institute Marques de Valdecilla (NTC0235832, NCT02534363), Instituto de Salud Carlos III, FIS 00/3095, 01/3129, PI020499, PI060507, PI10/00183, the SENY Fundació Research Grant (CI 2005‐0308007), the Fundación Marqués de Valdecilla (API07/011), MINECOSAF2013-46292-R, PSYSCAN (Exp.: HEALTH.2013.2.2.1-2_Grant agreement no. 603196). We want to particularly acknowledge the patients and the BioBankValdecilla (PT13/0010/0024) integrated in the Spanish National Biobanks Network for its collaboration. We thank IDIVAL Neuroimaging Unit for its help in the technical execution of this work. RSCZ: Supported in part by the RFBR (20-013-00748). SCORE: This study was supported in part by the SNSF (3232BO_119382). We thank the FePsy (Frueherkennung von Psychosen; early detection of psychosis) Study Group from the University of Basel, Department of Psychiatry, Switzerland, for the recruitment of the study participants. The FePsy Study was supported in part by grant no. SNF 3200-057216/1, ext./2, ext./3. SNUH: Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and the Korea Brain Research Institute (KBRI) basic research program through the KBRI, funded by the Ministry of Science, ICT & Future Planning (2019R1C1C1002457, 2020M3E5D9079910, 21-BR-03–01). SWIFT: Supported in part by the SNSF (320030_146789). TOP: Supported by the Research Council of Norway (#160181, 190311, 223273, 213837, 249711), the South-East Norway Health Authority (2014114, 2014097, 2017- 112), the Kristian Gerhard Jebsen Stiftelsen (SKGJ‐MED‐008), and the European Community’s Seventh Framework Programme (FP7/2007–2013), grant agreement no. 602450 (IMAGEMEND). UCISZ: Supported by the NIMH (R21MH097196 to T.G.M.v.E.). Data were processed by the UCI High-Performance Computing cluster (see FBIRN). UMCU: Supported by ZonMw (90802123, 91746370 to H.E.H.P., and 10-000-1001 to R.S.K.). UNIBA: Supported by grant funding from the Italian Ministry of Research (2017M7SZM8_004, PI A.B.; 2017K2NEF4, PI G.P.). UNIMAAS: Supported by ZonMw (91112002) and by a personal grant to T.v.A. (ZonMw-VIDI: 91712394). This clinical trial was registered in the Dutch clinical trial registry under ID: NTR5094 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR5094). Zurich: Funded by the SNSF.Peer reviewe
