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In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
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.
The acute care of stroke involves the administration of a clot-dissolving drug (thrombolysis) and/or its removal using endovascular clot retrieval. Earlier intervention results in significantly improved patient outcomes. Clinical assessment scores have limitations, and studies have shown that even the most robust scores have a reported false-negative rate of >20% for large vessel occlusive strokes that may be eligible for clot retrieval, while inappropriate bypass may delay delivery of thrombolysis.1 Quantitative Electroencephalography (QEEG) has been shown to have a very high sensitivity and specificity in the identification of acute stroke versus matched controls in an in-hospital setting.(2,3)
The SPIDER study commenced in Brisbane, Queensland on September 3, 2018, and is investigating the use of an EEG recorder to gather data on acute stroke patients presenting to a metropolitan ambulance service.
The data collected will guide the development of a simple numerical output reference to guide decision making. The data may aid in identifying large vessel occlusive stroke and patients eligible for endovascular intervention. The QEEG will provide a more accurate and cost-effective tool for the prehospital clinician over other imaging technologies and can guide early destination decisions. This presentation discusses the implementation of a pre-hospital research platform, integration with the clinical dispatch matrix, staff engagement, patient recruitment, and the success of the project so far.
In this article, I argue that audiocassette technology decentralized state-controlled Egyptian media long before the advent of al-Jazeera and the Internet. By enabling any citizen to become a cultural producer, as opposed to a mere consumer, the mass medium and its users sparked significant anxiety in the mid-to-late 20th century, when contentious cassette recordings led many local critics to assert that “vulgar” tapes were poisoning public taste, undermining high culture, and endangering Egyptian society. This article breaks down these arguments and shows that audiotapes actually broadcast a vast variety of voices. Thus, underlying many criticisms of cassette content, I contend, was not simply a concern for aesthetic sensibilities but a desire to dictate who created Egyptian culture during a time of tremendous change. By unpacking these discussions, this article harnesses Egypt as a case study to enhance prevailing investigations of sound, popular culture, and mass media in Middle East studies.
OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.