| 1. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 2. |
- Robba, C., et al.
(författare)
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Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients. Methods and analysis This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)-target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients' prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay. Ethics and dissemination The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.
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| 3. |
- Smith, K.A., et al.
(författare)
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Oxidation of atmospheric methane in Northern European soils, comparison with other ecosystems, and uncertainties in the global terrestrial sink
- 2000
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 6:7, s. 791-803
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the range and statistical distribution of oxidation rates of atmospheric CH4 in soils found in Northern Europe in an international study, and compares them with published data for various other ecosystems. It reassesses the size, and the uncertainty in, the global terrestrial CH4 sink, and examines the effect of land-use change and other factors on the oxidation rate. Only soils with a very high water table were sources of CH4, all others were sinks. Oxidation rates varied from 1 to nearly 200 µg CH4 m-2 h-1, annual rates for sites measured for =1 y were 0.1-9.1 kg CH4 ha-1 y-1, with a log-normal distribution (log-mean ~ 1.6 kg CH4 ha-1 y-1). Conversion of natural soils to agriculture reduced oxidation rates by two-thirds - closely similar to results reported for other regions. N inputs also decreased oxidation rates. Full recovery of rates after these disturbances takes > 100 y. Soil bulk density, water content and gas diffusivity had major impacts on oxidation rates. Trends were similar to those derived from other published work. Increasing acidity reduced oxidation, partially but not wholly explained by poor diffusion through litter layers which did not themselves contribute to the oxidation. The effect of temperature was small, attributed to substrate limitation and low atmospheric concentration. Analysis of all available data for CH4 oxidation rates in situ showed similar log-normal distributions to those obtained for our results, with generally little difference between different natural ecosystems, or between short-and longer-term studies. The overall global terrestrial sink was estimated at 29 Tg CH4 y-1, close to the current IPCC assessment, but with a much wider uncertainty range (7 to > 100 Tg CH4 y-1). Little or no information is available for many major ecosystems, these should receive high priority in future research.
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| 4. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 5. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 6. |
- Uijterwijk, Bas A., et al.
(författare)
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The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study
- 2024
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Ingår i: Annals of Surgical Oncology. - : SPRINGER. - 1068-9265 .- 1534-4681.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. Results: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. Conclusions: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
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| 7. |
- Uijterwijk, Bas A., et al.
(författare)
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The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study
- 2024
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Ingår i: British Journal of Cancer. - : SPRINGERNATURE. - 0007-0920 .- 1532-1827.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. Patients and methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). Results: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). Discussion: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.
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| 8. |
- White, H.D., et al.
(författare)
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Effects of alirocumab on types of myocardial infarction: Insights from the ODYSSEY OUTCOMES trial
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 40:33, s. 2801-2809
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Tidskriftsartikel (refereegranskat)abstract
- Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (=1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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