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- Kersten, CM, et al.
(författare)
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The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
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Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
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- Blomdin, Robin, et al.
(författare)
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Timing and dynamics of glaciation in the Ikh Turgen Mountains, Altai region, High Asia
- 2018
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Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 47, s. 54-71
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Tidskriftsartikel (refereegranskat)abstract
- Spanning the northern sector of High Asia, the Altai region contains a rich landform record of glaciation. We report the extent, chronologies, and dynamics of two paleoglaciers on opposite flanks of the Ikh Turgen mountains (In Russian: Chikhacheva Range), straddling the border between Russia and Mongolia, using a combination of remote sensing-based glacial geomorphological mapping, 10Be surface exposure dating, and geomorphometric analysis. On the eastern side (Mongolia), the Turgen-Asgat paleoglacier, with its potential for developing a large accumulation area (∼257 km2), expanded 40 km down valley, and mean ages from a latero-frontal moraine indicate deglaciation during marine oxygen isotope stage (MIS) 3 (45.1 ± 1.8 ka, n = 4) and MIS 2 (22.8 ± 3.3 ka, n = 5). These minimum age constraints are consistent with other 10Be glacial chronologies and paleoclimate records from the region, which indicates glacier culmination during cold and wet conditions coinciding with MIS 3 (piedmont-style glaciation; inferred for a few sites across the region) and glacier culmination during cold and dry conditions coinciding with MIS 2 (mainly valley-style glaciation; inferred from several sites across the region). On the western side (Russia), the Boguty paleoglacier had a smaller accumulation area (∼222 km2), and advanced 30 km down valley across a low gradient forefield. Surface exposure ages from two moraine complexes on this side of the mountains exhibit wide scatter (∼14–53 ka, n = 8), making paleoclimate inferences and comparison to other proxies difficult. Ice surface profile reconstructions imply that the two paleoglaciers likely shared an ice divide. © 2018 Elsevier B.V.
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- Blomdin, Robin, et al.
(författare)
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Evaluating the timing of former glacier expansions in the Tian Shan : A key step towards robust spatial correlations
- 2016
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 153, s. 78-96
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Tidskriftsartikel (refereegranskat)abstract
- The timing of past glaciation across the Tian Shan provides a proxy for past climate change in this critical area. Correlating glacial stages across the region is difficult but cosmogenic exposure ages have considerable potential. A drawback is the large observed scatter in Be-10 surface exposure data. To quantify the robustness of the dating, we compile, recalculate, and perform statistical analyses on sets of 10Be surface exposure ages from 25 moraines, consisting of 114 new and previously published ages. We assess boulder age scatter by dividing boulder groups into quality classes and rejecting boulder groups of poor quality. This allows us to distinguish and correlate robustly dated glacier limits, resulting in a more conservative chronology than advanced in previous publications. Our analysis shows that only one regional glacial stage can be reliably correlated across the Tian Shan, with glacier expansions occurring between 15 and 281 a during marine oxygen isotope stage (MIS) 2. However, there are examples of older more extensive indicators of glacial stages between MIS 3 and MIS 6. Paleoglacier extent during MIS 2 was mainly restricted to valley glaciation. Local deviations occur: in the central Kyrgyz Tian Shan paleoglaciers were more extensive and we propose that the topographic context explains this pattern. Correlation between glacial stages prior to late MIS 2 is less reliable, because of the low number of samples and/or the poor resolution of the dating. With the current resolution and spatial coverage of robustly-dated glacier limits we advise that paleoclimatic implications for the Tian Shan glacial chronology beyond MIS 2 are speculative and that continued work toward robust glacial chronologies is needed to resolve questions regarding drivers of past glaciation in the Tian Shan and Central Asia.
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| 20. |
- Buentke, E, et al.
(författare)
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Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
- 2011
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Ingår i: Blood Cancer Journal. - : Macmillan Publishers Limited. - 2044-5385. ; 1:e31, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.
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| 22. |
- Gribenski, Natacha, et al.
(författare)
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Re-evaluation of MIS 3 glaciation using cosmogenic radionuclide and single grain luminescence ages, Kanas Valley, Chinese Altai
- 2018
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 33:1, s. 55-67
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Tidskriftsartikel (refereegranskat)abstract
- Previous investigations observed a period of major glacial advances in Central Asia during marine oxygen isotope stage (MIS) 3 (57–29 ka), out of phase with global ice volume records. We have re-examined the Kanas moraine complex in the Altai Mountains of Central Asia, where an MIS 3 glaciation had been previously inferred. New and consistent cosmogenic exposure and single-grain luminescence ages indicate that the Kanas complex was formed during MIS 2 (29–12 ka), which brings its timing in line with the global ice volume record. We also identified a lateral moraine from a more extensive ice extent that dates to late MIS 5/MIS 4. To place our results in a wider contextual framework, we review the chronologies of another 26 proposed major MIS 3 glacial advances in Central Asia. For most of these sites, we find that the chronological data do not provide an unequivocal case for MIS 3 glaciation. Copyright © 2017 John Wiley & Sons, Ltd.
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| 24. |
- Kuchinskaya, E, et al.
(författare)
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Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles
- 2005
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Ingår i: European Journal of Haematology. - Oxford : Blackwell Publishing. - 0902-4441 .- 1600-0609. ; 74:6, s. 466-480
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis.METHODS: The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix.RESULTS: Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype.CONCLUSIONS: In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity.
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| 33. |
- Patton, H., et al.
(författare)
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Deglaciation of the Eurasian ice sheet complex
- 2017
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 169, s. 148-172
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Tidskriftsartikel (refereegranskat)abstract
- The Eurasian ice sheet complex (EISC) was the third largest ice mass during the Last Glacial Maximum with a span of over 4500 km and responsible for around 20 m of eustatic sea-level lowering. Whilst recent terrestrial and marine empirical insights have improved understanding of the chronology, pattern and rates of retreat of this vast ice sheet, a concerted attempt to model the deglaciation of the EISC honouring these new constraints is conspicuously lacking. Here, we apply a first-order, thermo-mechanical ice sheet model, validated against a diverse suite of empirical data, to investigate the retreat of the EISC after 23 ka BP, directly extending the work of Patton et al. (2016) who modelled the build-up to its maximum extent. Retreat of the ice sheet complex was highly asynchronous, reflecting contrasting regional sensitivities to climate forcing, oceanic influence, and internal dynamics. Most rapid retreat was experienced across the Barents Sea sector after 17.8 ka BP when this marine-based ice sheet disintegrated at a rate of similar to 670 gigatonnes per year (Gt a(-1)) through enhanced calving and interior dynamic thinning, driven by oceanic/atmospheric warming and exacerbated by eustatic sea-level rise. From 14.9 to 12.9 ka BP the EISC lost on average 750 Gt a(-1), peaking at rates >3000 Gt a(-1), roughly equally partitioned between surface melt and dynamic losses, and potentially contributing up to 2.5 m to global sea-level rise during Meltwater Pulse 1A. Independent glacio-isostatic modelling constrained by an extensive inventory of relative sea-level change corroborates our ice sheet loading history of the Barents Sea sector. Subglacial conditions were predominately temperate during deglaciation, with over 6000 subglacial lakes predicted along with an extensive subglacial drainage network. Moreover, the maximum EISC and its isostatic footprint had a profound impact on the proglacial hydrological network, forming the Fleuve Manche mega-catchment which had an area of similar to 2.5 x 10(6) km(2) and drained the present day Vistula, Elbe, Rhine and Thames rivers through the Seine Estuary. During the Bolling/Allerod oscillation after c. 14.6 ka BP, two major proglacial lakes formed in the Baltic and White seas, buffering meltwater pulses from eastern Fennoscandia through to the Younger Dryas when these massive proglacial freshwater lakes flooded into the North Atlantic Ocean. Deglaciation temporarily abated during the Younger Dryas stadial at 12.9 ka BP, when remnant ice across Svalbard, Franz Josef Land, Novaya Zemlya, Fennoscandia and Scotland experienced a short-lived but dynamic re-advance. The final stage of deglaciation converged on present day ice cover around the Scandes mountains and the Barents Sea by 8.7 ka BP, although the phas-lagged isostatic recovery still continues today. (C) 2017 The Authors. Published by Elsevier Ltd.
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| 34. |
- Piqeur, Floor, et al.
(författare)
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Development of a consensus-based delineation guideline for locally recurrent rectal cancer
- 2022
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 177, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Neoadjuvant chemoradiotherapy (nCRT) is used in locally recurrent rectal cancer (LRRC) to increase chances of a radical surgical resection. Delineation in LRRC is hampered by complex disease presentation and limited clinical exposure. Within the PelvEx II trial, evaluating the benefit of chemotherapy preceding nCRT for LRRC, a delineation guideline was developed by an expert LRRC team. Materials and methods: Eight radiation oncologists, from Dutch and Swedish expert centres, participated in two meetings, delineating GTV and CTV in six cases. Regions at-risk for re-recurrence or irradical resection were identified by eleven expert surgeons and one expert radiologist. Target volumes were evaluated multidisciplinary. Inter-observer variation was analysed. Results: Inter-observer variation in delineation of LRRC appeared large. Multidisciplinary evaluation per case is beneficial in determining target volumes. The following consensus regarding target volumes was reached. GTV should encompass all tumour, including extension into OAR if applicable. If the tumour is in fibrosis, GTV should encompass the entire fibrotic area. Only if tumour can clearly be distinguished from fibrosis, GTV may be reduced, as long as the entire fibrotic area is covered by the CTV. CTV is GTV with a 1 cm margin and should encompass all at-risk regions for irradical resection or re-recurrence. CTV should not be adjusted towards other organs. Multifocal recurrences should be encompassed in one CTV. Elective nodal delineation is only advised in radiotherapy-naïve patients. Conclusion: This study provides a first consensus-based delineation guideline for LRRC. Analyses of re-recurrences is needed to understand disease behaviour and to optimize delineation guidelines accordingly.
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| 36. |
- Rohrer, Julia M., et al.
(författare)
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Putting the Self in Self-Correction : Findings From the Loss-of-Confidence Project
- 2021
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Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 16:6, s. 1255-1269
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Tidskriftsartikel (refereegranskat)abstract
- Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose. Far from evaluating new evidence dispassionately and infallibly, individual scientists often cling stubbornly to prior findings. Here we explore the dynamics of scientific self-correction at an individual rather than collective level. In 13 written statements, researchers from diverse branches of psychology share why and how they have lost confidence in one of their own published findings. We qualitatively characterize these disclosures and explore their implications. A cross-disciplinary survey suggests that such loss-of-confidence sentiments are surprisingly common among members of the broader scientific population yet rarely become part of the public record. We argue that removing barriers to self-correction at the individual level is imperative if the scientific community as a whole is to achieve the ideal of efficient self-correction.
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| 38. |
- Schmiegelow, K, et al.
(författare)
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Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia.
- 2010
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 24:2, s. 345-54
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to <10% of the patients and provided a 5-year risk of isolated CNS relapse of 2.6%. Improved risk stratification and chemotherapy have eliminated the previous independent prognostic significance of gender, CNS leukemia and translocation t(1;19)(q23;p13), whereas the post-induction level of minimal residual disease (MRD) has emerged as a new risk grouping feature. Infant leukemia, high leukocyte count, T-lineage immunophenotype, translocation t(4;11)(q21;q23) and hypodiploidy persist to be associated with lower cure rates. To reduce the overall toxicity of the treatment, including the risk of therapy-related second malignant neoplasms, the current NOPHO ALL-2008 protocol does not include CNS irradiation in first remission, the dose of 6-mercaptopurine is reduced for patients with low thiopurine methyltransferase activity, and the protocol restricts the use of hematopoietic stem cell transplantation in first remission to patients without morphological remission after induction therapy or with high levels of MRD after 3 months of therapy.
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| 40. |
- Stokes, Chris R., et al.
(författare)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Forskningsöversikt (refereegranskat)abstract
- Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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| 41. |
- Toksvang, LN, et al.
(författare)
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Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0-45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol
- 2022
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22:1, s. 483-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA critical challenge in current acute lymphoblastic leukemia (ALL) therapy is treatment intensification in order to reduce the relapse rate in the subset of patients at the highest risk of relapse. The year-long maintenance phase is essential in relapse prevention. The Thiopurine Enhanced ALL Maintenance (TEAM) trial investigates a novel strategy for ALL maintenance.MethodsTEAM is a randomized phase 3 sub-protocol to the ALLTogether1 trial, which includes patients 0–45 years of age with newly diagnosed B-cell precursor or T-cell ALL, and stratified to the intermediate risk-high (IR-high) group, in 13 European countries. In the TEAM trial, the traditional methotrexate (MTX)/6-mercaptopurine (6MP) maintenance backbone (control arm) is supplemented with low dose (2.5–12.5 mg/m2/day) oral 6-thioguanine (6TG) (experimental arm), while the starting dose of 6MP is reduced from 75 to 50 mg/m2/day. A total of 778 patients will be included in TEAM during ~ 5 years. The study will close when the last included patient has been followed for 5 years from the end of induction therapy. The primary objective of the study is to significantly improve the disease-free survival (DFS) of IR-high ALL patients by adding 6TG to 6MP/MTX-based maintenance therapy. TEAM has 80% power to detect a 7% increase in 5-year DFS through a 50% reduction in relapse rate. DFS will be evaluated by intention-to-treat analysis. In addition to reducing relapse, TEAM may also reduce hepatotoxicity and hypoglycemia caused by high levels of methylated 6MP metabolites. Methotrexate/6MP metabolites will be monitored and low levels will be reported back to clinicians to identify potentially non-adherent patients.DiscussionTEAM provides a novel strategy for maintenance therapy in ALL with the potential of improving DFS through reducing relapse rate. Potential risk factors that have been considered include hepatic sinusoidal obstruction syndrome/nodular regenerative hyperplasia, second cancer, infection, and osteonecrosis. Metabolite monitoring can potentially increase treatment adherence in both treatment arms.Trial registrationEudraCT, 2018–001795-38. Registered 2020-05-15,Clinicaltrials.gov,NCT04307576. Registered 2020-03-13,https://clinicaltrials.gov/ct2/show/NCT04307576
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| 49. |
- Hall, Adrian M., et al.
(författare)
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Glacial ripping: geomorphological evidence from Sweden for a new process of glacial erosion
- 2020
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Ingår i: Geografiska Annaler Series a-Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 2:4, s. 333-53
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Tidskriftsartikel (refereegranskat)abstract
- In low relief Precambrian gneiss terrain in eastern Sweden, abraded bedrock surfaces were ripped apart by the Fennoscandian Ice Sheet. The resultantboulder spreadsare covers of large, angular boulders, many with glacial transport distances of 1-100 m. Boulder spreads occur alongside partly disintegrated roches moutonnees and associated fracture caves, and are associated withdisrupted bedrock, which shows extensive fracture dilation in the near surface. These features are distributed in ice-flow parallel belts up to 10 km wide and extend over distances of >500 km. Our hypothesis is that the assemblage results from (1) hydraulic jacking and bedrock disruption, (2) subglacial ripping and (3) displacement, transport and final deposition of boulders. Soft sediment fills indicate jacking and dilation of pre-existing bedrock fractures by groundwater overpressure below the ice sheet. Overpressure reduces frictional resistance along fractures. Where ice traction overcomes this resistance, the rock mass strength is exceeded, resulting in disintegration of rock surfaces and ripping apart into separate blocks. Further movement and deposition create boulder spreads and moraines. Short boulder transport distances and high angularity indicate that glacial ripping operated late in the last deglaciation. The depths of rock mobilized in boulder spreads are estimated as 1-4 m. This compares with 0.6-1.6 m depths of erosion during the last glaciation derived from cosmogenic nuclide inventories of samples from bedrock surfaces without evidence of disruption. Glacially disrupted and ripped bedrock is also made ready for removal by future ice sheets. Henceglacial rippingis a highly effective process of glacial erosion.
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| 50. |
- Hermelijn, S, et al.
(författare)
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Development of a core outcome set for congenital pulmonary airway malformations: study protocol of an international Delphi survey
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:4, s. e044544-
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Tidskriftsartikel (refereegranskat)abstract
- A worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM.Methods and analysisThis study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus.Ethics and disseminationElectronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM.
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