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"Jensen, Karen"
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Dietary non-starch polysaccharides impair immunity to enteric nematode infection
Background
The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory (
Cichorium intybus
) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health.
Results
Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more diverse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm
Heligmosomoides polygyrus
. Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm
Trichuris muris
, concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher
T. muris
burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow
T. muris
expulsion.
Conclusions
Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.
Journal Article
Continuous Ethanol Fermentation of Pretreated Lignocellulosic Biomasses, Waste Biomasses, Molasses and Syrup Using the Anaerobic, Thermophilic Bacterium Thermoanaerobacter italicus Pentocrobe 411
Lignocellosic ethanol production is now at a stage where commercial or semi-commercial plants are coming online and, provided cost effective production can be achieved, lignocellulosic ethanol will become an important part of the world bio economy. However, challenges are still to be overcome throughout the process and particularly for the fermentation of the complex sugar mixtures resulting from the hydrolysis of hemicellulose. Here we describe the continuous fermentation of glucose, xylose and arabinose from non-detoxified pretreated wheat straw, birch, corn cob, sugar cane bagasse, cardboard, mixed bio waste, oil palm empty fruit bunch and frond, sugar cane syrup and sugar cane molasses using the anaerobic, thermophilic bacterium Thermoanaerobacter Pentocrobe 411. All fermentations resulted in close to maximum theoretical ethanol yields of 0.47-0.49 g/g (based on glucose, xylose, and arabinose), volumetric ethanol productivities of 1.2-2.7 g/L/h and a total sugar conversion of 90-99% including glucose, xylose and arabinose. The results solidify the potential of Thermoanaerobacter strains as candidates for lignocellulose bioconversion.
Journal Article
Revisiting beta‐2 microglobulin as a prognostic marker in diffuse large B‐cell lymphoma
Background Several clinical prognostic models for diffuse large B‐cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN‐IPI), and models incorporating beta‐2 microglobulin (β2M). However, the role of β2M in DLBCL patients is not fully understood. Methods We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with β2M and NCCN‐IPI performed better than the International Prognostic Indexes (IPI, age‐adjusted IPI, and revised IPI). Five‐year overall survival for high‐ and low‐risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN‐IPI. In univariate analysis, higher levels of β2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (β2M‐NCCN‐IPI) by adding β2M to NCCN‐IPI (c‐index 0.708) with improved discriminatory ability compared to NCCN‐IPI (c‐index 0.698, p < 0.05) and 5‐year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high‐intermediate, low‐intermediate and low‐risk group, respectively. Conclusion International Prognostic Indices, except for NCCN‐IPI, fail to accurately discriminate risk groups in the rituximab era. β2M, a readily available marker, could improve the discriminatory performance of NCCN‐IPI and should be re‐evaluated in the development setting of future models for DLBCL. Beta‐2 microglobulin (β2M) has been sporadically incorporated in prognostic models for diffuse large B‐cell lymphoma (DLBCL). We compared the prognostic discriminative ability of four existing DLBCL models with International Prognostic Indices. Moreover, we developed and validated a new model from the largest population investigating this marker so far, indicating the necessity to include β2M in future studies when analyzing prognostic markers in DLBCL.
Journal Article
Prognostic indices in diffuse large B-cell lymphoma: a population-based comparison and validation study of multiple models
Currently, the International Prognostic Index (IPI) is the most used and reported model for prognostication in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). IPI-like variations have been proposed, but only a few have been validated in different populations (e.g., revised IPI (R-IPI), National Comprehensive Cancer Network IPI (NCCN-IPI)). We aimed to validate and compare different IPI-like variations to identify the model with the highest predictive accuracy for survival in newly diagnosed DLBCL patients. We included 5126 DLBCL patients treated with immunochemotherapy with available data required by 13 different prognostic models. All models could predict survival, but NCCN-IPI consistently provided high levels of accuracy. Moreover, we found similar 5-year overall survivals in the high-risk group (33.4%) compared to the original validation study of NCCN-IPI. Additionally, only one model incorporating albumin performed similarly well but did not outperform NCCN-IPI regarding discrimination (c-index 0.693). Poor fit, discrimination, and calibration were observed in models with only three risk groups and without age as a risk factor. In this extensive retrospective registry-based study comparing 13 prognostic models, we suggest that NCCN-IPI should be reported as the reference model along with IPI in newly diagnosed DLBCL patients until more accurate validated prognostic models for DLBCL become available.
Journal Article
A new tetraploid variety of Cryptocoryne ciliata (Araceae) from Sarawak
A new, tetraploid variety of Cryptocoryne ciliata (Roxb.) Fisch. ex Schott from Sarawak, Malaysia, is described and illustrated: C. ciliata var. bogneri N. Jabobsen. The ecology, morphology and chromosome numbers of C. ciliata are discussed. The new variety is compared with the other two varieties of the species, C. ciliata var. ciliata and C. ciliata var. latifolia Rataj, and an identification key is provided. Citation: Jacobsen N., Bastmeijer J. D., Jensen K. R. & Ørgaard M. 2018: A new tetraploid variety of Cryptocoryne ciliata (Araceae) from Sarawak. – Willdenowia 48: 425–431. doi: https://doi.org/10.3372/wi.48.48312 Version of record first published online on 1 December 2018 ahead of inclusion in December 2018 issue.
Journal Article
Health care utilisation following childhood acute lymphoblastic leukaemia: a population-based matched cohort study
ObjectivesSurvival among children diagnosed with acute lymphoblastic leukaemia (ALL) has increased considerably. However, morbidity in survivors constitutes a potential increasing burden not limited to secondary health care. Our objectives were to compare health care utilisation, including both primary and secondary health care, between childhood ALL survivors and matched references up to 15 years after curative treatment. Moreover, to increase knowledge on survivors’ health service seeking behaviour as time from treatment elapsed.Design and settingA Danish population-based matched cohort study linking multiple nationwide registries.Participants675 cases, diagnosed with childhood (1.0–17.9 years) ALL between 1994 and 2015, and 6750 matched references sampled randomly from the source population (matched on age, gender and geographical region).Primary outcome measuresRepeated consultations in general practice and hospital (outpatient and inpatient) estimated as yearly rates from 2.5 years after diagnosis and onwards. We compared cases and references with yearly incidence rate ratios (IRRs) from negative binomial regression models.ResultsSurvivors of childhood ALL had a mean number of yearly daytime contacts in general practice of 4.75 (95% CI 4.41 to 5.11) the first year, corresponding to an IRR of 1.85 (95% CI 1.71 to 2.00); decreasing to 1.16 (1.01 to 1.34) after 15 years, and without significant impact of gender (p=0.894) or age (p=0.399). For hospital contacts, ALL survivors had a mean number of yearly contacts of 14.21 (13.38–15.08) the first year, corresponding to an IRR of 31.50 (28.29–35.07); decreasing to 2.42 (1.59–3.68) after 15 years. No differences were found across calendar time.ConclusionsALL survivors used significantly more health care services across sectors than the reference population. Decreasing use over 15 years illustrated the dynamics of health care needs; this knowledge may inform the future organisation of integrated follow-up programmes.Trial registration numberNCT03985826.
Journal Article
Health care utilisation preceding relapse or second malignant neoplasm after childhood acute lymphoblastic leukaemia: a population-based matched cohort study
ObjectivesTo investigate health care utilisation including both primary and secondary health care 6 months before the diagnosis of a relapse or a second malignant neoplasm (SMN) in survivors of childhood acute lymphoblastic leukaemia (ALL).Design and settingA Danish population-based matched cohort study linking multiple nationwide registries.ParticipantsParticipants were recruited from a total of 622 childhood ALL 2.5-year event-free survivors diagnosed between 1994 and 2015. Cases were survivors developing a relapse or an SMN and references were survivors still in first remission. Each case was matched with five references on age, sex, treatment protocol and risk group.Primary outcome measuresConsultations in general practice and hospital the last 6 months before relapse or SMN. Cases and references were compared with monthly incidence rate ratios (IRRs) from negative binomial regression models.ResultsOf the 622 childhood ALL survivors, 60 (9.6%) developed a relapse (49) or an SMN (11) and 295 matched references were identified. Health care utilisation in general practice increased among cases the last month before the event compared with references with an IRR of 2.71 (95% CI 1.71 to 4.28). Data showed a bimodal structure with a significantly increased number of visits 4, 5 and 6 months before the event. Hospital health care utilisation increased 2 months before the event in cases with an IRR of 5.01 (3.78 to 6.63) the last month before the event and an IRR of 1.94 (1.32 to 2.85) the second-last month comparing cases and references.ConclusionsSurvivors of childhood ALL developing a relapse or an SMN have a short period of increased health care utilisation before diagnosis. At hospital, this might be explained by pre-diagnostic examinations. In general practice, data suggest a bimodal structure with children later developing a relapse having more contacts also half a year before the relapse, suggesting that there could be early warnings.
Journal Article
Shadow organizing and imitation: new foci for research
Purpose
Shadow organizing refers to the emergence of parallel arrangements that sit alongside and imitate mainstream or conventional ways of organizing. It can be a response to challenges that require new ways of working without abandoning what is valuable about conventional arrangements. However, the processes through which shadow organizing is accomplished are not well understood; there is a need to go beyond traditional notions of mimicry and metaphor. The paper aims to discuss these issues.
Design/methodology/approach
This paper demonstrates how a Tardean approach to imitation can address this gap. It deploys imitation as an explanatory concept, based on contemporary readings of Tarde, as well as understandings of organizing as an unfolding process. Child and Family Centres in Tasmania (Australia), are used as an example of shadow organizing, delivering integrated health and education services in an emerging parallel arrangement.
Findings
The analysis highlights an imitation dynamic which is far from straightforward mimicry. Rather, it comprises repetition and generation of difference. This dynamic is conceptualized in Tardean fashion as three patterns: the imitation of ideas before expression; the selective nature of imitation; and insertion of the old alongside the new.
Originality/value
The paper moves beyond metaphors of shadow organizing, and understandings of shadow organizing as mimicry. Conceptualizing imitation in an alternative way, it contributes fresh insights into how shadow organizing is accomplished. This enriches and expands the conceptual apparatus for researchers wishing to understand the betwixt and between of shadow organizing.
Journal Article
A comparative study of standardized quantitative and visual assessment for predicting tumor volume and outcome in newly diagnosed diffuse large B-cell lymphoma staged with 18F-FDG PET/CT
BackgroundSemi-automated quantitative measurement of metabolic tumor volume (MTV) for prognosis in diffuse large B-Cell lymphoma (DLBCL) has gained considerable interest lately. However, simple tumor volume measures may be inadequate for assessment of prognosis in DLBCL as other characteristics such as growth pattern and metabolic heterogeneity may be just as important. In addition, MTV measurements require delineation of tumor lesions by semi-automated software, which can be time-consuming. We hypothesized that a simple visual assessment of tumor volume performs as well as standardized MTV measurements in DLBCL prognostication.Materials and methodsQuantitative and visual analyses of pre-therapy 18F-FDG PET/CT scans in 118 patients with newly diagnosed DLBCL were conducted. Quantitative analyses were performed using Hermes TumourFinder® to obtain MTV2.5 (SUV 2.5 cut-off) and MTV41 (41% SUVmax isocontour cut-off). Visual assessments included a binary prediction (good/poor prognosis) as well as tumor burden based on a visual analog scale (MTVVAS) and an estimated volume (eMTV). Three experienced nuclear medicine physicians who were blinded to clinical outcome performed visual evaluations. Progression-free survival was evaluated by Kaplan-Meier curves and log-rank test. Inter-observer variability was evaluated by Fleiss’ kappa for multiple observers.ResultsIn the quantitative analysis, a ROC-determined MTV2.5 cut-off (log-rank p = 0.11) seemed to outperform MTV41 (log-rank p = 0.76) for PFS prediction. TLG2.5 (log-rank p = 0.14) and TLG41 (log-rank p = 0.34) were not associated with outcomes. By visual analysis, all three reviewers were able to stratify patients into good/poor prognosis (reviewer A log-rank p = 0.002, reviewer B log-rank p = 0.016, and reviewer C log-rank p = 0.012) with fair inter-observer agreement (Fleiss’ kappa 0.47). MTVVAS and eMTV were not consistently correlated with the outcome.ConclusionPredictions of outcome after first-line treatment for DLBCL were surprisingly good when left to the unsupervised, subjective judgment of experienced readers of lymphoma 18F-FDG-PET/CT. The study highlights the importance of non-standardized clinical judgments and shows potential loss of valuable prognostic information when relying solely on semi-automated MTV measurements.
Journal Article