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The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Electronic cigarettes, often referred to as e-cigarettes, have established a considerable market in North America over the last decade. In parallel to this trend, there has been a surge of e-cigarette battery explosions reported in the general media. Given the growing number of such events, acute care physicians should recognize the associated risks and injury patterns and initiate appropriate treatment. This report presents two cases of burn injuries from e-cigarette battery explosions requiring surgical management. The accompanying comprehensive literature review highlights the emerging importance of e-cigarettes as an aetiology of burn injury.
The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.
The data in this analysis were derived from a study of patients meeting DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/d (n=109) or placebo (n=100). We defined “irritability” as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.
Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (–22.6 vs. –9.5, p<0.0001, effect size [ES]=1.4) and without (–19.9 vs. –13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (–1.4 vs. –0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (–1.0 vs. –0.3, p=0.0002, ES=1.2).
In our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.
Mixed states address the relationships between episodes and the course of an illness, presenting significant clinical challenges. Recurrent affective disorders were described thousands of years ago as dimensional disturbances of the basic elements of behavior, combining the characteristics of what we would now consider manic and depressive episodes. It was recognized from the beginning that combinations of depressive and manic features are associated with a severe illness course, including increased suicide risk. Early descriptions of affective disorders formulated them as systemic illnesses, a concept supported by more recent data. Descriptions of affective disorders and their course, including mixed states, became more systematic during the 19th century. Structured criteria achieved importance with evidence that, in addition to early onset, frequent recurrence, and comorbid problems, mixed states had worse treatment outcomes than other episodes. In contrast to 2000 years of literature on recurrent affective episodes and mixed states, the unipolar–bipolar disorder distinction was formalized in the mid-20th century. Mixed-state criteria, initially developed for bipolar disorder, ranged from fully combined depression and mania to the DSM–5 criteria, no longer limited to bipolar disorder, of a primary depressive or manic episode with at least three symptoms of the other episode type. The challenges involved in understanding and identifying mixed states center largely on what drives them, including (1) their formulation as either categorical or dimensional constructs, (2) the specificity of their relationships to depressive or manic episodes, and (3) specificity for bipolar versus major depressive disorder. Their existence challenges the distinction between bipolar and major depressive disorders. The challenges involved in identifying the underlying physiological mechanisms go to the heart of these questions.
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.
Alan Trounson, Californian Institute for Regenerative Medicine, San Francisco, CA, USA,
Roger Gosden, Jamestowne Bookworks,Williamsburg, VA, USA,
Ursula Eichenlaub-Ritter, Faculty of Biology, Institute of Gene Technology/Microbiology, University of Bielefeld, Bielefeld, Germany
When approached by Nick Dunton of Cambridge University Press to edit the second edition of The Biology and Pathology of the Oocyte, my response was an emphatic yes, providing my co-editor Roger Gosden could be enticed from retirement. He agreed and we both wanted Ursula Eichenlaub-Ritter to be the third editor because we admired her expertise in the basic biology of the oocyte and her ability to get the job done. There has been incredible progress in the knowledge of the oocyte and applications for medicine that have regularly appeared since the first edition. We considered the areas of reproductive technology – IVF – and the areas of reprogramming somatic cell phenotype as spin-offs of the progress made in oocyte biology. Both these areas received Nobel Prizes in the last few years and are included in the contributions for the second edition. We were fortunate to have John Gurdon open the second edition the year (2013) after he won the Nobel Prize in Physiology or Medicine. He and his coauthor set the scene for a rather different perspective of the power and influence of the oocyte in modern biology. The contributors invited for the second edition are exceptional in their areas of oocyte biology, pathology, and applications to biotechnology and medicine. We think they have captured the excitement of the fast-moving frontier of the oocyte field.
The second edition will enthuse the reader interested in how the oocyte is formed, its function, and the underlying mechanisms of what is the most extraordinary cell in the body. It remains the germinal link from generation to generation and must undergo the most elaborate series of changes to be ready to accept the genomic contribution of the most differentiated of all cells – the sperm. The oocyte must then enter the developmental program that enables an organism to arise with extremes in patterning and lineage differentiation consistent with the species of origin. In this exquisitely crafted program of development, it is possible to intervene to manipulate the oocyte for purposes of solving human infertility, to clone animals, develop pluripotent embryonic stem cells, and reprogram cell commitment in fully differentiated cells in animals including the human – so-called induced pluripotent stem cells (iPSCs). As a consequence we are able to address human infertility and avoid some of the worst inheritable genetic diseases, enable advances in selective animal breeding, and potentially address many human pathologies by using stem cell therapies.