132 research outputs found

    Gene flow at the leading range edge: the long-term consequences of isolation in European Beech (Fagus sylvatica L. Kuhn)

    Get PDF
    Aim Isolation is expected to lead to negative impacts on populations due to a reduction in effective population size and gene flow, exacerbating the effects of genetic drift, which might be stronger in peripheral and fragmented populations. Fagus sylvatica (European beech) in southern Sweden presents a gradient of isolation towards the leading range edge of the species. We sought to determine the impact of long‐term isolation on genetic diversity and population genetic structure within populations of this species. Location Samples were obtained from 14 sites towards the northern edge of the native range of beech in Sweden. Taxon Fagaceae. Methods Using historical sources, we obtained area‐ and distance‐based measures of isolation. We measured genetic diversity and structure by using nuclear microsatellite marker data, and performed parentage analysis to estimate external pollen‐mediated gene flow. We implemented a partial least squares regression to determine the effects of isolation on each of the genetic diversity estimators and the measures of external pollen‐mediated gene flow. Results Long‐term isolation generally had a negative impact on genetic diversity, which is exacerbated over time, further affecting progeny and suggesting that isolated populations are subject to strong genetic drift, possibly due to the combination of founder events and persistent small population sizes. Bayesian cluster analysis revealed that isolation was also acting as a barrier to gene flow in the north‐eastern distribution of beech. Main conclusions Isolation at the leading range edge of beech in Sweden has created gradients of contemporary gene flow within the species. The long‐term cumulative effects of isolation on this wind‐pollinated tree species and its negative impacts on genetic diversity and gene flow, could lead to inbreeding depression and higher extinction risk where populations remain small and isolated

    Anatomy-Aware Self-supervised Fetal MRI Synthesis from Unpaired Ultrasound Images

    Full text link
    Fetal brain magnetic resonance imaging (MRI) offers exquisite images of the developing brain but is not suitable for anomaly screening. For this ultrasound (US) is employed. While expert sonographers are adept at reading US images, MR images are much easier for non-experts to interpret. Hence in this paper we seek to produce images with MRI-like appearance directly from clinical US images. Our own clinical motivation is to seek a way to communicate US findings to patients or clinical professionals unfamiliar with US, but in medical image analysis such a capability is potentially useful, for instance, for US-MRI registration or fusion. Our model is self-supervised and end-to-end trainable. Specifically, based on an assumption that the US and MRI data share a similar anatomical latent space, we first utilise an extractor to determine shared latent features, which are then used for data synthesis. Since paired data was unavailable for our study (and rare in practice), we propose to enforce the distributions to be similar instead of employing pixel-wise constraints, by adversarial learning in both the image domain and latent space. Furthermore, we propose an adversarial structural constraint to regularise the anatomical structures between the two modalities during the synthesis. A cross-modal attention scheme is proposed to leverage non-local spatial correlations. The feasibility of the approach to produce realistic looking MR images is demonstrated quantitatively and with a qualitative evaluation compared to real fetal MR images.Comment: MICCAI-MLMI 201

    Case vignettes for a European comparison of structures and common pathways to formal care

    Get PDF
    Background: People with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time. Objectives: Description and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project. Materials and methods: The German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario. Results: A transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system. Conclusion: Enhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.publishersversionpublishe

    Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST)

    Get PDF
    Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies

    Reducing uncertainty in health-care resource allocation

    Get PDF
    A key task for health policymakers is to optimise the outcome of health care interventions. The pricing of a new generation of cancer drugs, in combination with limited health care resources, has highlighted the need for improved methodology to estimate outcomes of different treatment options. Here we introduce new general methodology, which for the first time employs continuous hazard functions for analysis of survival data. Access to continuous hazard functions allows more precise estimations of survival outcomes for different treatment options. We illustrate the methodology by calculating outcomes for adjuvant treatment of gastrointestinal stromal tumours with imatinib mesylate, which selectively inhibits the activity of a cancer-causing enzyme and is a hallmark representative for the new generation of cancer drugs. The calculations reveal that optimal drug pricing can generate all win situations that improve drug availability to patients, make the most of public expenditure on drugs and increase pharmaceutical company gross profits. The use of continuous hazard functions for analysis of survival data may reduce uncertainty in health care resource allocation, and the methodology can be used for drug price negotiations and to investigate health care intervention thresholds. Health policy makers, pharmaceutical industry, reimbursement authorities and insurance companies, as well as clinicians and patient organisations, should find the methodology useful

    Post-Covid-19 Irritable Bowel Syndrome

    Get PDF
    Objectives The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p < 0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls

    Low Densities of Serotonin and Peptide YY Cells in the Colon of Patients with Irritable Bowel Syndrome

    Get PDF
    Background The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients. Aims To investigate a possible abnormality in the colonic endocrine cells of IBS patients. Methods A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis. Results Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin- immunoreactive cells were too few to enable reliable quantification

    Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

    Get PDF
    Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor
    corecore