Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and ...segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone AUC: 0.44, accuracy: 46%). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.
Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments via cross-walls, and to ...septation and release of unicellular spores. Specific determinants for cross-wall formation and the importance of hyphal compartmentalization for Streptomyces development are largely unknown. Here we show that SepX, an actinobacterial-specific protein, is crucial for both cell division modes in Streptomyces venezuelae. Importantly, we find that sepX-deficient mutants grow without cross-walls and that this substantially impairs the fitness of colonies and the coordinated progression through the developmental life cycle. Protein interaction studies and live-cell imaging suggest that SepX contributes to the stabilization of the divisome, a mechanism that also requires the dynamin-like protein DynB. Thus, our work identifies an important determinant for cell division in Streptomyces that is required for cellular development and sporulation.
Introduction
Recent studies suggesting an increased cancer risk with glucose-lowering agents have received widespread publicity. The objectives of this study were to evaluate the comparability in ...underlying cancer risk and patterns of cancer risk over time with different glucose-lowering agents.
Methods
The General Practice Research Database (GPRD) was used to identify cohorts of new users. Cancer outcomes were obtained from the GPRD, Hospital Episode Statistics and cancer registries. Relative rates of cancer comparing different glucose-lowering agents were estimated using Poisson regression.
Results
A total of 206,940 patients was identified. There was no difference in cancer risk and quartile for HbA
1c
value. There were differences in cancer incidence in the first 6 months after starting treatment (adjusted relative rate of 0.83 95% CI 0.70, 0.99 with thiazolidinediones, 1.34 95% CI 1.19, 1.51 with sulfonylureas and 1.79 95% CI 1.53, 2.10 with insulin, compared with metformin). Insulin users had decreasing cancer incidence over time (adjusted relative rate of 0.58 95% CI 0.50, 0.68 during months 6–24, relative rate of 0.50 95% CI 0.42, 0.59 during months 25–60 and relative rate of 0.48 95% CI 0.40, 0.59 during months 60+) compared with months 0–6 after starting insulin. Similar patterns were found with sulfonylureas and metformin. There were no increases over time with insulin glargine (A21Gly, B31Arg, B32Arg human insulin; relative rate of 0.70 95% CI 0.52, 0.95, 0.77 95% CI 0.56, 1.07 and 0.60 95% CI 0.36, 1.02, respectively, for 6–24, 25–60 and >60 months).
Conclusions
These findings do not provide evidence of either beneficial or adverse effects of glucose-lowering agents on cancer risk and are consistent with changes in diabetes treatment in the few months prior to the diagnosis of cancer.
Cerebral metabolism is tightly regulated and fundamental for healthy neurological function. There is increasing evidence that alterations in this metabolism may be a precursor and early biomarker of ...later stage disease processes. Proton magnetic resonance spectroscopy (1H-MRS) is a powerful tool to non-invasively assess tissue metabolites and has many applications for studying the normal and diseased brain. However, the technique has limitations including low spatial and temporal resolution, difficulties in discriminating overlapping peaks, and challenges in assessing metabolic flux rather than steady-state concentrations. Hyperpolarized carbon-13 magnetic resonance imaging is an emerging clinical technique that may overcome some of these spatial and temporal limitations, providing novel insights into neurometabolism in both health and in pathological processes such as glioma, stroke and multiple sclerosis. This review will explore the growing body of pre-clinical data that demonstrates a potential role for the technique in assessing metabolism in the central nervous system. There are now a number of clinical studies being undertaken in this area and this review will present the emerging clinical data as well as the potential future applications of hyperpolarized 13C magnetic resonance imaging in the brain, in both clinical and pre-clinical studies.
Washing macroalgae is a ‘standard’ initial pre-treatment step, reported in a number of papers on biofuel production from macroalgae. Washing removes particulate matter; however, in this study, we ...show that washing may also have an adverse effect on the water-soluble carbohydrate contents present in the macroalgae, potentially reducing the quantity of the biofuel produced. This has major implications if macroalgae are to be considered as a feedstock for biofuel and platform chemicals. We compared washed and unwashed material from summer and winter harvests which were subsequently dried by three methods as follows: (1) immediate oven drying, (2) freezing, then oven drying and (3) freeze-drying. The proportions of the water-soluble carbohydrates were assessed and a decrease of up to 49.3 % seen in the laminarin content of those washed. Oven drying also resulted in some degradation of the laminarin with approximately 10× increase in glucose concentrations compared to freeze-drying. When this material was used as a substrate for biofuel production, unwashed Laminaria digitata generated a higher concentration of ethanol in all the differently dried summer samples and two thirds of winter samples, suggesting that not washing is advantageous unless other factors are involved, e.g. a large quantity of particulate material is present on the macroalgae. In contrast, washed samples used in an anaerobic digestion study gave higher methane yields in two thirds of the drying treatments than the unwashed, possibly due to lower salt-tolerance in the anaerobic microbial consortia, so a pre-washing step could be considered more suitable for this conversion route.
Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2+ monocytes are recruited from peripheral blood to wound ...tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2‐deficient mice (CCR2−/−) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2−/− and WT mice revealed a significant decrease in inflammatory, Ly6CHi recruited monocyte/macrophages in CCR2−/− wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2−/− wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2+/+ and CCR2−/− mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2+/+ and CCR2−/− mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2‐deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.
Upon initial tissue injury, CCL2, one of the primary ligands for CCR2, is increased in the wound. This ligand binds the CCR2 receptors that are present on Ly6CHi monocytes, recruiting these cells to the wound, allowing initiation of the macrophage‐mediated inflammatory phase of wound healing.
The adipocyte-derived hormone adiponectin promotes metabolic and cardiovascular health. Circulating adiponectin increases in lean states such as caloric restriction (CR), but the reasons for this ...paradox remain unclear. Unlike white adipose tissue (WAT), bone marrow adipose tissue (MAT) increases during CR, and both MAT and serum adiponectin increase in many other clinical conditions. Thus, we investigated whether MAT contributes to circulating adiponectin. We find that adiponectin secretion is greater from MAT than WAT. Notably, specific inhibition of MAT formation in mice results in decreased circulating adiponectin during CR despite unaltered adiponectin expression in WAT. Inhibiting MAT formation also alters skeletal muscle adaptation to CR, suggesting that MAT exerts systemic effects. Finally, we reveal that both MAT and serum adiponectin increase during cancer therapy in humans. These observations identify MAT as an endocrine organ that contributes significantly to increased serum adiponectin during CR and perhaps in other adverse states.
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•Secretion of adiponectin is greater from MAT than WAT•Blocking MAT expansion during CR suppresses increased serum adiponectin•Blocking MAT expansion alters skeletal muscle adaptation to CR•Both MAT and circulating adiponectin increase in humans undergoing cancer therapy
Adiponectin is a paradoxical adipokine because, in lean states, while white adipose tissue shrinks, circulating adiponectin concentrations increase. Now, Cawthorn et al. reveal that, during caloric restriction, increased bone marrow adipose tissue (MAT) is a major source of adiponectin, and blocking MAT expansion impacts metabolic adaptations in skeletal muscle.
To ascertain stakeholders' agreement and disagreement about inter-professional collaboration (IPC) when supporting the child with a developmental language disorder (DLD) in school.
Two rounds of an ...online Delphi survey were undertaken with a purposive sample of 26 participants (researchers, practitioners and parents). Topics were informed by the views of children engaged in an earlier phase of the research. Agreement was set at an inter-quartile range of 1, with level of agreement measured using a five-point semantic differential scale. Qualitative data were examined using content analysis.
There was strong agreement across the stakeholder groups about the child-led goals of IPC. Stakeholders also agreed that DLD is best viewed as a learning difference rather than a disorder. We identified ambivalence across the groups about the right of the child with DLD to have influence in decision-making about supports in school.
We propose that IPC should be viewed as a means of ensuring the inclusion of the child in school. A shift in focus from remediating perceived deficits of the child, to affecting change in classroom practice, is also indicated. The need to reinforce the unconditional right of the child to have influence in decisions about supports is highlighted. Implications for IPC when meeting the needs of children with a developmental disability in school are outlined.
IMPLICATIONS FOR REHABILITATION
The goal of inter-professional collaboration should be to ensure the inclusion of the child with a developmental disability in school.
Interventions delivered in school should focus on changing practice in the classroom, rather than on the child's perceived deficits.
The child with a developmental disability should be given influence in collaborative decision-making to ensure supports are relevant and responsive to their needs.
Effective collaboration between speech and language therapists (SLTs) and teachers is essential in meeting the needs of children with developmental language disorders in school, but it is difficult ...to achieve. Currently, many children receive inadequate speech and language therapy services and/or support in school. The aim of this study was to engage key stakeholders (SLTs, teachers, parents and children with DLD) in the co-design of their ideal speech and language therapy service and support in school. The study was undertaken in order to inform the development of a conceptual model to guide collaborative practice when working with this population.
A qualitative study involving a diverse range of key stakeholders and using appreciative inquiry. This is a method which enables those involved to construct their 'ideal' about a topic of interest. Recruitment was carried out using purposive sampling. We conducted focus groups with practitioners (SLTs and teachers) and parents as well as semi-structured interviews with children who have DLD using 'draw and tell' techniques. A total of five focus groups and nine interviews were conducted with participants (n = 27).
The children described their ideal supports as those which enabled them to connect, contribute and achieve. They describe ways in which environmental barriers in school needed to be addressed to allow them to do so. The professionals primarily described ways in which the language skills of the child could be improved. Both parents and practitioner groups described the importance of strengthening networks between service providers and service users. They also highlighted the need to promote a collaborative culture if stakeholders are to work effectively together across sectors.
There were differences in perspectives about the ways in which speech and language therapy services and supports could be improved, demonstrating the importance of engaging a diverse group of stakeholders. Of note were the unique insights the children brought about the barriers they faced as a result of their difficulties. Based on our findings we propose that children should be given influence in decisions about the supports that they receive in school. Implications for policy, research and practice are discussed.
Summary
Osteoporosis and fractures are common features of alkaptonuria.
Introduction
A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and ...fractures in AKU.
Methods
Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated.
Results
Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (
p
< 0.05). CT LS showed an inverse relationship with fractures (
R
= − 0.28;
p
< 0.05). CT LS was significantly lower in the fracture group (
p
< 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (
p
< 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (
p
< 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (
p
< 0.05).
Conclusions
Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.
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