Mapping track density changes in nigrostriatal and extranigral pathways in Parkinson's disease

peer reviewedHighlights First whole-brain probabilistic tractography study in Parkinson's disease High quality diffusion-weighted images (120 gradient directions, b = 2500 s/mm2) Voxel-based group analysis comparing early-stage patients and controls Abnormal reconstructed track density in the nigrostriatal pathway and brainstem Track density also increased in limbic and cognitive circuits

The ReIMAGINE multimodal warehouse: using artificial intelligence for accurate risk stratification of prostate cancer

Introduction. Prostate cancer (PCa) is the most frequent cancer diagnosis in men worldwide. Our ability to identify those men whose cancer will decrease their lifespan and/or quality of life remains poor. The ReIMAGINE Consortium has been established to improve PCa diagnosis. Materials and methods. MRI will likely become the future cornerstone of the risk-stratification process for men at risk of early prostate cancer. We will, for the first time, be able to combine the underlying molecular changes in PCa with the state-of-the-art imaging. ReIMAGINE Screening invites men for MRI and PSA evaluation. ReIMAGINE Risk includes men at risk of prostate cancer based on MRI, and includes biomarker testing. Results. Baseline clinical information, genomics, blood, urine, fresh prostate tissue samples, digital pathology and radiomics data will be analysed. Data will be de-identified, stored with correlated mpMRI disease endotypes and linked with long term follow-up outcomes in an instance of the Philips Clinical Data Lake, consisting of cloud-based software. The ReIMAGINE platform includes application programming interfaces and a user interface that allows users to browse data, select cohorts, manage users and access rights, query data, and more. Connection to analytics tools such as Python allows statistical and stratification method pipelines to run profiling regression analyses. Discussion. The ReIMAGINE Multimodal Warehouse comprises a unique data source for PCa research, to improve risk stratification for PCa and inform clinical practice. The de-identified dataset characterized by clinical, imaging, genomics and digital pathology PCa patient phenotypes will be a valuable resource for the scientific and medical community

Effectiveness of High Fidelity Video-Assisted Real-Time Simulation: A Comparison of Three Training Methods for Acute Pediatric Emergencies

Background. Video-assisted real-time simulation (VARS) offers the possibility of developing competence in acute medicine in a realistic and safe environment. We investigated the effectiveness of the VARS model and compared it with educational methods like Problem-Based Learning (PBL) and Pediatric Advanced Life Support (PALS). Methods. 45 fourth-year medical students were randomized for three educational methods. Level of knowledge and self-efficacy were measured before and after intervention. Clinical performance was measured by a blinded observer using a video checklist of prescripted scenarios on a high-fidelity simulator. Results. Knowledge test and self-efficacy scores improved significantly (P < 0.001) without differences between educational groups. The VARS group showed significantly (P < 0.05) higher scores on both postintervention scenarios concerning structure and time. Conclusion. VARS training is an effective educational method teaching pediatric acute care skills in the undergraduate curriculum. When compared to PBL and PALS training, VARS training appears to be superior in enhancing short-term clinical performance

Spectral Theory of Sparse Non-Hermitian Random Matrices

Sparse non-Hermitian random matrices arise in the study of disordered physical systems with asymmetric local interactions, and have applications ranging from neural networks to ecosystem dynamics. The spectral characteristics of these matrices provide crucial information on system stability and susceptibility, however, their study is greatly complicated by the twin challenges of a lack of symmetry and a sparse interaction structure. In this review we provide a concise and systematic introduction to the main tools and results in this field. We show how the spectra of sparse non-Hermitian matrices can be computed via an analogy with infinite dimensional operators obeying certain recursion relations. With reference to three illustrative examples --- adjacency matrices of regular oriented graphs, adjacency matrices of oriented Erd\H{o}s-R\'{e}nyi graphs, and adjacency matrices of weighted oriented Erd\H{o}s-R\'{e}nyi graphs --- we demonstrate the use of these methods to obtain both analytic and numerical results for the spectrum, the spectral distribution, the location of outlier eigenvalues, and the statistical properties of eigenvectors.Comment: 60 pages, 10 figure

A randomised controlled trial of intravenous zoledronic acid in malignant pleural disease: A proof of principle pilot study

© 2015 Clive et al. Introduction: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods: We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results: Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions: This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration: UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

External quality assessment of SARS-CoV-2-sequencing: An ESGMD-SSM pilot trial across 15 European laboratories

Objective: This first pilot on external quality assessment (EQA) of SARS-CoV-2 whole genome sequencing, initiated by the ESCMID Study Group for Genomic and Molecular Diagnostics (ESGMD) and Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing.Methods: Ten samples with varying viral loads were sent out to 15 clinical laboratories who had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centres were compared on were identification of 1) SNPs and indels, 2) Pango lineages, and 3) clusters between samples.Results: The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to varying depth (up to 100-fold difference across centres). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignment. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data.Conclusions: The pilot EQA was an overall success. It was able to show the high quality of participating labs and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.</p

MRI findings in acute hyperammonemic encephalopathy: Three cases of different etiologies

Acute hyperammonemic encephalopathy is a rare but life-threatening condition that might complicate liver disease as well as non-hepatic conditions. It can lead to coma and death, secondary to brain edema and intracranial hypertension. We present three cases of acute hyperammonemic encephalopathy of different etiologies and the observed brain MRI findings. Symmetrical extensive cortical signal abnormalities, typically involving the insular and cingulate cortices, often showing restricted diffusion, are commonly described. These specific imaging features should be recognized by the radiologist since prompt treatment of the condition is paramount.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A stroke mimic with left-hemispheric leptomeningeal vessel paucity and hypoperfusion

In the neuroimaging workup of a suspected ischemic stroke, the involvement of more than one arterial territory without an anatomical substrate should raise the suspicion of a stroke mimic. We report the case of a 61-year-old male with a new-onset headache and transient phasic disturbances who presented a pattern of vascular abnormalities characterized by left-hemispheric leptomeningeal vessel paucity and hypoperfusion