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| 2. |
- Tierney, W., et al.
(author)
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A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
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In: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
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Journal article (peer-reviewed)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
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| 3. |
- Delios, A., et al.
(author)
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Examining the generalizability of research findings from archival data
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Journal article (peer-reviewed)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 5. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 8. |
- Vögel, H. -J, et al.
(author)
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Emotion-awareness for intelligent vehicle assistants : A research agenda
- 2018
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In: Proceedings - International Conference on Software Engineering. - New York, NY, USA : IEEE Computer Society. - 9781450357395 ; , s. 11-15
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Conference paper (peer-reviewed)abstract
- EVA1 is describing a new class of emotion-aware autonomous systems delivering intelligent personal assistant functionalities. EVA requires a multi-disciplinary approach, combining a number of critical building blocks into a cybernetics systems/software architecture: emotion aware systems and algorithms, multimodal interaction design, cognitive modelling, decision making and recommender systems, emotion sensing as feedback for learning, and distributed (edge) computing delivering cognitive services.
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| 10. |
- Bakalis, Serafim, et al.
(author)
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Perspectives from CO+RE : How COVID-19 changed our food systems and food security paradigms.
- 2020
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In: Current Research in Food Science. - : Elsevier BV. - 2665-9271. ; 3, s. 166-172
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Journal article (peer-reviewed)abstract
- Within a few weeks the world has changed, at the time this text is written (May 2020) more than 3.5 million people have been confirmed cases of COVID-19 and estimations propose up to a hundred times the number of actually infected. A third of the global population is on lockdown and a large part of our global economic activity has stopped. Food and access to food has played a visual role in portraying the impact of the outbreak on our society, with images of empty supermarket shelves appearing in mainstream media. In some countries closed schools resulted in many children not having access to free meals and mobilised a number of charities. While parts of the world are now exiting lockdown and measures start relaxing the near future remains uncertain with more waves of the pandemic expected. Given that there is currently no evidence to show that transmission of COVID-19 could occur through food or food packaging there has been limited discussion on the issue, implications and potential future scenarios within the wider food science community.Within the food research community, up to the pandemic crisis the discourse has been dominated with design and manufacture of healthy and safe foods. The main issues are relevant to sustainability, circular economy, energy and water efficiency, climate friendly practices of products and processes. Efficiency has been the focus, but resilience has not been a significant issue so far. The term food system resilience has been defined by Tendalla (Tendalla et al., 2015) as ‘capacity over time of a food system and its units at multiple levels, to provide sufficient, appropriate and accessible food to all, in the face of various and even unforeseen disturbances’. We believe that in the future we will continue to see similar pressures in the food system, e.g., comparable pandemics, effects of climate change on food production, and that resilience will become of major importance.This commentary aims to present a reflection from the past, considering the present situation to provide thoughts on the actions needed to ensure resilient food systems.
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| 12. |
- Gathercole, L. L., et al.
(author)
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AKR1D1 knockout mice develop a sex-dependent metabolic phenotype
- 2022
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In: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 253:3, s. 97-113
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Journal article (peer-reviewed)abstract
- Steroid 5 beta-reductase (AKR1D1) plays important role in hepatic bile acid synthesis and glucocorticoid clearance. Bile acids and glucocorticoids are potent metabolic regulators, but whether AKR1D1 controls metabolic phenotype in vivo is unknown. Akr1d1(-/-) mice were generated on a C57BL/6 background. Liquid chromatography/mass spectrometry, metabolomic and transcriptomic approaches were used to determine effects on glucocorticoid and bile add homeostasis. Metabolic phenotypes including body weight and composition, lipid homeostasis, glucose tolerance and insulin tolerance were evaluated. Molecular changes were assessed by RNA-Seq and Western blotting. Male Akr1d1(-/-) mice were challenged with a high fat diet (60% kcal from fat) for 20 weeks. Akr1d1(-/-) mice had a sex-specific metabolic phenotype. At 30 weeks of age, male, but not female, Akr1d1(-/-) mice were more insulin tolerant and had reduced lipid accumulation in the liver and adipose tissue yet had hypertriglyceridemia and increased intramuscular triacylglycerol. This phenotype was associated with sexually dimorphic changes in bile acid metabolism and composition but without overt effects on circulating glucocorticoid levels or glucocorticoid-regulated gene expression in the liver. Male Akr1d1(-/-) mice were not protected against diet-induced obesity and insulin resistance. In conclusion, this study shows that AKR1D1 controls bile acid homeostasis in vivo and that altering its activity can affect insulin tolerance and lipid homeostasis in a sex-dependent manner.
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| 13. |
- Williams-Gray, Caroline H, et al.
(author)
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Serum immune markers and disease progression in an incident Parkinson's disease cohort (ICICLE-PD)
- 2016
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:7, s. 995-1003
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Journal article (peer-reviewed)abstract
- BACKGROUND: The immune system is a promising therapeutic target for disease modification in Parkinson's disease (PD), but appropriate immune-related biomarkers must be identified to allow patient stratification for trials and tracking of therapeutic effects. The objective of this study was to investigate whether immune markers in peripheral blood are candidate prognostic biomarkers through determining their relationship with disease progression in PD.METHODS: Serum samples were collected in incident PD cases and age-matched controls. Subjects were clinically evaluated at baseline and 18 and 36 months. Ten cytokines and C-reactive protein were measured, with data reduction using principal-component analysis, and relationships between component scores and motor (MDS Unified Parkinson's Disease Rating Scale - part 3) and cognitive (Mini Mental State Examination [MMSE]) measures of disease severity/progression were investigated.RESULTS: TNF-α, IL1-β, IL-2, and IL-10 were higher in PD (n = 230) than in controls (n = 93), P ≤ 0.001). Principal-component analysis of log-transformed data resulted in a 3-component solution explaining 51% of the variance. Higher "proinflammatory" and lower "anti-inflammatory" component scores were associated with more rapid motor progression over 36 months (P < 0.05), and higher "proinflammatory" component scores were associated with lower MMSE at all times (P < 0.05). Multiple linear regression analysis with adjustment for covariates confirmed "anti-inflammatory" component score was the strongest predictor of slower motor progression (β = -0.22, P = 0.002), whereas proinflammatory cytokines were associated with lower baseline MMSE (β = -0.175, P = 0.007).CONCLUSIONS: Serum immune marker profile is predictive of disease progression in PD and hence a potential prognostic biomarker. However, interventional trials are needed to clarify whether peripheral immune changes causally contribute to the progression of PD. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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| 16. |
- Fjell, J, et al.
(author)
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In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons
- 1999
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In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 81:2, s. 803-810
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Journal article (peer-reviewed)abstract
- In vivo NGF deprivation reduces SNS expression and TTX-R sodium currents in IB4-negative DRG neurons. Recent evidence suggests that changes in sodium channel expression and localization may be involved in some pathological pain syndromes. SNS, a tetrodotoxin-resistant (TTX-R) sodium channel, is preferentially expressed in small dorsal root ganglion (DRG) neurons, many of which are nociceptive. TTX-R sodium currents and SNS mRNA expression have been shown to be modulated by nerve growth factor (NGF) in vitro and in vivo. To determine whether SNS expression and TTX-R currents in DRG neurons are affected by reduced levels of systemic NGF, we immunized adult rats with NGF, which causes thermal hypoalgesia in rats with high antibody titers to NGF. DRG neurons cultured from rats with high antibody titers to NGF, which do not bind the isolectin IB4 (IB4−) but do express TrkA, were studied with whole cell patch-clamp and in situ hybridization. Mean TTX-R sodium current density was decreased from 504 ± 77 pA/pF to 307 ± 61 pA/pF in control versus NGF-deprived neurons, respectively. In comparison, the mean TTX-sensitive sodium current density was not significantly different between control and NGF-deprived neurons. Quantification of SNS mRNA hybridization signal showed a significant decrease in the signal in NGF-deprived neurons compared with the control neurons. The data suggest that NGF has a major role in the maintenance of steady-state levels of TTX-R sodium currents and SNS mRNA in IB4− DRG neurons in adult rats in vivo.
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| 19. |
- Jones, Robert P., et al.
(author)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Journal article (peer-reviewed)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 20. |
- Neoptolemos, John P., et al.
(author)
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Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4) : a multicentre, open-label, randomised, phase 3 trial
- 2017
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10073, s. 1011-1024
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Journal article (peer-reviewed)abstract
- Background: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.Methods: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1: 1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m(2) gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m(2) oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.Findings: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28.0 months (95% CI 23.5-31.5) compared with 25.5 months (22.7-27.9) in the gemcitabine group (hazard ratio 0.82 [95% CI 0.68-0.98], p=0.032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group.Interpretation: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.
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| 21. |
- O'Hurley, Gillian, et al.
(author)
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Investigation of molecular alterations of AKT-3 in triple-negative breast cancer
- 2014
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In: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 64:5, s. 660-670
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Journal article (peer-reviewed)abstract
- Aims Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer (BC) deaths, owing to its intrinsic aggressiveness and a lack of treatment options, especially targeted therapies. Thus, there is an urgent need for the development of better targeted treatments for TNBC. Molecular alteration of AKT-3 was previously reported in oestrogen receptor (ER)-positive BC. AKT-3 has also been suggested to play a role in hormone-unresponsive BC. The aim of this study was to investigate molecular alterations of AKT-3 in TNBC, to perform associated survival analysis, and to compare these findings with the incidence of AKT-3 molecular alterations in ER-positive BC. Results Our study revealed AKT-3 amplification and deletions in 11% (9/82) and 13% (11/82) of TNBCs, respectively. In contrast, 1% (2/209) of ER-positive BCs were found to have AKT-3 amplifications and deletions. A higher prevalence of AKT-3 copy number gains was observed in TNBC [26% (21/82)] than in ER-positive BC [9% (19/209)]. AKT-3 amplification together with Akt-3 protein expression was negatively associated with recurrence-free survival in TNBC. Furthermore, a negative association between high AKT-3 copy number and recurrence-free survival was observed. Conclusion AKT-3 amplification could represent a potentially relevant oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to Akt-3 inhibitors.
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| 22. |
- Reid, Cameron J, et al.
(author)
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A role for ColV plasmids in the evolution of pathogenic Escherichia coli ST58
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- Escherichia coli ST58 has recently emerged as a globally disseminated uropathogen that often progresses to sepsis. Unlike most pandemic extra-intestinal pathogenic E. coli (ExPEC), which belong to pathogenic phylogroup B2, ST58 belongs to the environmental/commensal phylogroup B1. Here, we present a pan-genomic analysis of a global collection of 752 ST58 isolates from diverse sources. We identify a large ST58 sub-lineage characterized by near ubiquitous carriage of ColV plasmids, which carry genes encoding virulence factors, and by a distinct accessory genome including genes typical of the Yersiniabactin High Pathogenicity Island. This sub-lineage includes three-quarters of all ExPEC sequences in our study and has a broad host range, although poultry and porcine sources predominate. By contrast, strains isolated from cattle often lack ColV plasmids. Our data indicate that ColV plasmid acquisition contributed to the divergence of the major ST58 sub-lineage, and different sub-lineages inhabit poultry, swine and cattle.
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| 23. |
- Zhu, Min, et al.
(author)
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Braided Convolutional Self-orthogonal Codes with Double Sliding Window Decoding
- 2023
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In: 2023 12th International Symposium on Topics in Coding, ISTC 2023. - 9798350326116
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Conference paper (peer-reviewed)abstract
- In this paper, we investigate a class of braided convolutional codes (BCCs), where the component codes are convolutional self-orthogonal codes (CSOCs), called braided convolutional self-orthogonal codes. Compared to conventional BCCs, the advantages of braided CSOCs include the availability of several low-complexity decoding methods and the relative ease of extending these methods to high rates More specifically, to construct high-rate braided codes, it is necessary to use higher-rate component codes, which results in exponentially higher decoding complexity with conventional BCJR decoding, whereas the complexity of the CSOC decoding methods proposed here grows only linearly with rate. In particular, we introduce a double sliding window decoding method based on belief propagation (BP) for braided CSOCs, which exhibits good performance while maintaining low-complexity decoding for the higher rates required in many applications.
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