| 1. |
|
|
| 2. |
- Heyckendorf, J, et al.
(author)
-
Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
- 2021
-
In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 58:3
-
Journal article (peer-reviewed)abstract
- The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.MethodsAdult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.Results50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
|
|
| 3. |
- Fan, Y., et al.
(author)
-
The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice
- 2023
-
In: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 8, s. 787-802
-
Journal article (peer-reviewed)abstract
- Anorexia nervosa (AN) is an eating disorder with a high mortality. About 95% of cases are women and it has a population prevalence of about 1%, but evidence-based treatment is lacking. The pathogenesis of AN probably involves genetics and various environmental factors, and an altered gut microbiota has been observed in individuals with AN using amplicon sequencing and relatively small cohorts. Here we investigated whether a disrupted gut microbiota contributes to AN pathogenesis. Shotgun metagenomics and metabolomics were performed on faecal and serum samples, respectively, from a cohort of 77 females with AN and 70 healthy females. Multiple bacterial taxa (for example, Clostridium species) were altered in AN and correlated with estimates of eating behaviour and mental health. The gut virome was also altered in AN including a reduction in viral-bacterial interactions. Bacterial functional modules associated with the degradation of neurotransmitters were enriched in AN and various structural variants in bacteria were linked to metabolic features of AN. Serum metabolomics revealed an increase in metabolites associated with reduced food intake (for example, indole-3-propionic acid). Causal inference analyses implied that serum bacterial metabolites are potentially mediating the impact of an altered gut microbiota on AN behaviour. Further, we performed faecal microbiota transplantation from AN cases to germ-free mice under energy-restricted feeding to mirror AN eating behaviour. We found that the reduced weight gain and induced hypothalamic and adipose tissue gene expression were related to aberrant energy metabolism and eating behaviour. Our 'omics' and mechanistic studies imply that a disruptive gut microbiome may contribute to AN pathogenesis. Faecal metagenomics and serum metabolomics reveal compositional and functional alterations in the gut microbiota of women with anorexia nervosa, and faecal transplants could transfer an anorexia-associated phenotype to germ-free mice.
|
|
| 4. |
- Muir Wood, David, 1949, et al.
(author)
-
Fibres and roots for soil improvement
- 2015
-
In: Geomechanics from Micro to Macro - Proceedings of the TC105 ISSMGE International Symposium on Geomechanics from Micro to Macro, IS-Cambridge 2014. - : CRC Press. - 9781138027077 ; 2, s. 1503-1508
-
Conference paper (peer-reviewed)abstract
- Observing the experimental interaction of flexible fibres and granular soils provides inspiration for the development of continuum models for the behaviour of fibre/soil mixtures. The detailed experimental observations come from mixtures of sand with flexible polypropylene fibres but the principles are believed to be relevant also for soils containing flexible plant roots. Two features are particularly important: the distribution of orientations of fibres (no method of preparation produces an isotropic distribution) and the allowance for the volume of void space not only occupied but also influenced by the presence of the fibres. As the soil-fibre mixture deforms, the straining of the soil generates fibre stresses in favourably oriented fibres. A simple shear element is used as a quasi-one-dimensional demonstrator platform for the development of this model. Pedagogically such an element has a number of desirable benefits: it represents a familiar configuration in which phenomena such as dilation and friction can be directly observed; and it is straightforward to convert the model for application to axisymmetric or general stress conditions.
|
|
| 5. |
- Muir Wood, David, 1949, et al.
(author)
-
Fibres and soils: A route towards modelling of root-soil systems
- 2016
-
In: Soils and Foundations. - : Elsevier BV. - 0038-0806. ; 56:5, s. 765-778
-
Journal article (peer-reviewed)abstract
- The addition of flexible fibres to granular, cohesionless soils, has a marked influence on the stress:strain and volumetric response. Experimental observations provide inspiration for the development of continuum models for the mechanical, pre-failure behaviour of these fibre/soil mixtures. Such generic models and the deduced mechanisms of response should be applicable to other combinations of soils and flexible fibres such as plant roots. Two features are particularly important: the distribution of the orientations of fibres (no method of preparation produces an isotropic distribution) and the allowance for the volume of void space not only occupied, but also influenced, by the presence of the fibres. A simple shear element is used as a quasi-one-dimensional demonstrator platform for the presentation of the continuum constitutive model. Such an element represents a familiar configuration in which phenomena, such as dilation and friction, can be directly observed. A basic constitutive model for sand is adapted to this simple shear element; the fibres are added as a separate component able to withstand tension but without flexural stiffness. As the soil-fibre mixture deforms, the straining of the soil generates stresses in favourably oriented fibres. The model is used to clarify some aspects of the response of the fibre-soil mixtures: the influence of fibres on the volumetric behaviour; the existence and nature of asymptotic states; and the stress dilatancy relationship.
|
|
