Generating synthetic fjord bathymetry for coastal Greenland

Bed topography is a critical boundary for the numerical modelling of ice sheets and ice-ocean interactions. A persistent issue with existing topography products for the bed of the Greenland Ice Sheet and surrounding sea floor is the poor representation of coastal bathymetry, especially in regions of floating ice and near the grounding line. Sparse data coverage, and the resultant coarse resolution at the ice-ocean boundary, poses issues in our ability to model ice flow advance and retreat from the present position. In addition, as fjord bathymetry is known to exert strong control on ocean circulation and ice-ocean forcing, the lack of bed data leads to an inability to model these processes adequately. Since the release of the last complete Greenland bed topography-bathymetry product, new observational bathymetry data have become available. These data can be used to constrain bathymetry, but many fjords remain completely unsampled and therefore poorly resolved. Here, as part of the development of the next generation of Greenland bed topography products, we present a new method for constraining the bathymetry of fjord systems in regions where data coverage is sparse. For these cases, we generate synthetic fjord geometries using a method conditioned by surveys of terrestrial glacial valleys as well as existing sinuous feature interpolation schemes. Our approach enables the capture of the general bathymetry profile of a fjord in north-west Greenland close to Cape York, when compared to observational data. We validate our synthetic approach by demonstrating reduced overestimation of depths compared to past attempts to constrain fjord bathymetry. We also present an analysis of the spectral characteristics of fjord centrelines using recently acquired bathymetric observations, demonstrating how a stochastic model of fjord bathymetry could be parameterised and used to create different realisations.This study was supported by UK NERC grant NE/M000869/1

Multimodal neuroimaging in presurgical evaluation of childhood epilepsy

In pre-surgical evaluation of pediatric epilepsy, the combined use of multiple imaging modalities for precise localization of the epileptogenic focus is a worthwhile endeavor. Advanced neuroimaging by high field Magnetic resonance imaging (MRI), diffusion tensor images, and MR spectroscopy have the potential to identify subtle lesions. 18F-FDG positron emission tomography and single photon emission tomography provide visualization of metabolic alterations of the brain in the ictal and interictal states. These techniques may have localizing value for patients which exhibit normal MRI scans. Functional MRI is helpful for non-invasively identifying areas of eloquent cortex. These advances are improving our ability to noninvasively detect epileptogenic foci which have gone undetected in the past and whose accurate localization is crucial for a favorable outcome following surgical resection

The interpretation of low mood and worry by high users of secondary care with medically unexplained symptoms

DA - 20111021 IS - 1471-2296 (Electronic) IS - 1471-2296 (Linking) LA - eng PT - Journal Article SB - IMPeer reviewedPublisher PD

Polypharmacy among anabolic-androgenic steroid users: A descriptive metasynthesis

Background: As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published. Method: We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines. Results: A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n = 22), followed by Sweden (n = 7), England only (n = 5), and the United Kingdom (n = 4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement. Conclusions: Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy

MRI compared to conventional diagnostic work-up in the detection and evaluation of invasive lobular carcinoma of the breast: a review of existing literature

Item does not contain fulltextPURPOSE: The clinical diagnosis and management of invasive lobular carcinoma (ILC) of the breast presents difficulties. Magnetic resonance imaging (MRI) has been proposed as the imaging modality of choice for the evaluation of ILC. Small studies addressing different aspects of MRI in ILC have been presented but no large series to date. To address the usefulness of MRI in the work-up of ILC, we performed a review of the currently published literature. MATERIALS AND METHODS: We performed a literature search using the query "lobular AND (MRI OR MR OR MRT OR magnetic)" in the Cochrane library, PubMed and scholar.google.com, to retrieve all articles that dealt with the use of MRI in patients with ILC. We addressed sensitivity, morphologic appearance, correlation with pathology, detection of additional lesions, and impact of MRI on surgery as different endpoints. Whenever possible we performed meta-analysis of the pooled data. RESULTS: Sensitivity is 93.3% and equal to overall sensitivity of MRI for malignancy in the breast. Morphologic appearance is highly heterogeneous and probably heavily influenced by interreader variability. Correlation with pathology ranges from 0.81 to 0.97; overestimation of lesion size occurs but is rare. In 32% of patients, additional ipsilateral lesions are detected and in 7% contralateral lesions are only detected by MRI. Consequently, MRI induces change in surgical management in 28.3% of cases. CONCLUSION: This analysis indicates MRI to be valuable in the work-up of ILC. It provides additional knowledge that cannot be obtained by conventional imaging modalities which can be helpful in patient treatment

How patients understand depression associated with chronic physical disease - A systematic review

Background: Clinicians are encouraged to screen people with chronic physical illness for depression. Screening alone may not improve outcomes, especially if the process is incompatible with patient beliefs. The aim of this research is to understand peoples beliefs about depression, particularly in the presence of chronic physical disease. Methods: A mixed method systematic review involving a thematic analysis of qualitative studies and quantitative studies of beliefs held by people with current depressive symptoms. MEDLINE, EMBASE, PSYCHINFO, CINAHL, BIOSIS, Web of Science, The Cochrane Library, UKCRN portfolio, National Research Register Archive, Clinicaltrials.gov and OpenSIGLE were searched from database inception to 31st December 2010. A narrative synthesis of qualitative and quantitative data, based initially upon illness representations and extended to include other themes not compatible with that framework. Results: A range of clinically relevant beliefs was identified from 65 studies including the difficulty in labeling depression, complex causal factors instead of the biological model, the roles of different treatments and negative views about the consequences of depression. We found other important themes less related to ideas about illness: the existence of a self-sustaining depression spiral; depression as an existential state; the ambiguous status of suicidal thinking; and the role of stigma and blame in depression. Conclusions: Approaches to detection of depression in physical illness need to be receptive to the range of beliefs held by patients. Patient beliefs have implications for engagement with depression screening

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Clonally expanded mitochondrial DNA deletions within the choroid plexus in multiple sclerosis

OBJECTIVE: Mitochondrial DNA deletions (Δ-mtDNA) are implicated in the pathogenesis of multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD) and ageing. Given the diffuse nature of inflammation in MS, aim of this study was to determine whether Δ-mtDNA caused respiratory deficient cells in excess of age within choroid plexus (CP) and ongoing mutagenesis or clonal expansion accounted for the respiratory deficiency in MS. METHODS: Respiratory chain complex IV and complex II activity was determined sequentially using histochemistry. Δ-mtDNA were characterized using real time PCR, long range PCR, sequencing and single molecule PCR. Sources of reactive oxygen and nitrogen species (RONS) were explored using immunohistochemistry. RESULTS: Respiratory deficient cells (lacking complex IV and with intact complex II activity) within CP epithelium were in excess of age in MS, PD and AD. Subunit-I of complex IV was lacking to a greater extent in MS than controls. Percentage of respiratory deficient cells harboring >50% heteroplasmy level of Δ-mtDNA was significantly greater in MS than PD, AD and controls. Long range PCR and sequencing confirmed Δ-mtDNA. Single molecule PCR identified clonally expanded Δ-mtDNA in MS, despite an increase in sources of RONS. INTERPRETATION: Our findings establish clonal expansion of Δ-mtDNA causing respiratory deficiency in MS and the extraparenchymal intracranial location indicated the potential to involve multiple cell types. Understanding factors that influence clonal expansion of Δ-mtDNA, a molecular link between inflammation and delayed cellular energy failure, may identify potential therapeutic targets for progressive forms of MS as well as other neurodegenerative disorders

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD