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Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17–18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17–18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19–20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body’s physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.
This paper assesses how Westerners depicted Chinese entrepreneurship in the late Qing period. The paper, which is based on a range of primary sources in English, Portuguese, and French, shows that Western views of Chinese entrepreneurs were highly diverse and that while some contemporary authors viewed Chinese entrepreneurship through an Orientalist lens, others rejected this paradigm by stressing that Chinese people, or at least some subsets of the Han Chinese population, were extremely entrepreneurial. Another group of authors modified the Orientalist stereotype of Chinese stagnation by suggesting that Chinese businesspeople were capable of the lower entrepreneurial functions (e.g., simple arbitrage) but not the higher branches of entrepreneurship, which involved innovation and creative destruction. These entrepreneurial functions were, ethnocentrically, regarded as the domain of Westerners. The paper may extend our understanding about how the past still affects our current perception of Chinese entrepreneurship. It also develops our understanding of the cultural histories of entrepreneurship and Sino-Western business.
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.
Electroconvulsive therapy (ECT) has long been used in the treatment of patients with neuropsychiatric disorders and continues to be a valuable option for a variety of conditions. The range of conditions for which ECT has been used is broad, but in many instances there is a common indication such as the treatment of psychosis, depression or catatonia occurring in conjunction with the primary neuropsychiatric presentation. Substantial, systematically acquired data supports the use of ECT in the functional psychoses (as set out in Chapters 3–11) but the complexity of additional underlying pathology prevents simple inferences being made about the efficacy of ECT in neuropsychiatric conditions. Regrettably, the evidence for ECT as a treatment for neuropsychiatric disorders is generally low grade, mostly comprising case reports, case series and retrospective and observational studies rather than double-blind randomised controlled trials.
A number of applications utilise the energy focussing potential of imploding shells to dynamically compress matter or magnetic fields, including magnetised target fusion schemes in which a plasma is compressed by the collapse of a liquid metal surface. This paper examines the effect of fluid rotation on the Rayleigh–Taylor (RT) driven growth of perturbations at the inner surface of an imploding cylindrical liquid shell which compresses a gas-filled cavity. The shell was formed by rotating water such that it was in solid body rotation prior to the piston-driven implosion, which was propelled by a modest external gas pressure. The fast rise in pressure in the gas-filled cavity at the point of maximum convergence results in an RT unstable configuration where the cavity surface accelerates in the direction of the density gradient at the gas–liquid interface. The experimental arrangement allowed for visualisation of the cavity surface during the implosion using high-speed videography, while offering the possibility to provide geometrically similar implosions over a wide range of initial angular velocities such that the effect of rotation on the interface stability could be quantified. A model developed for the growth of perturbations on the inner surface of a rotating shell indicated that the RT instability may be suppressed by rotating the liquid shell at a sufficient angular velocity so that the net surface acceleration remains opposite to the interface density gradient throughout the implosion. Rotational stabilisation of high-mode-number perturbation growth was examined by collapsing nominally smooth cavities and demonstrating the suppression of small spray-like perturbations that otherwise appear on RT unstable cavity surfaces. Experiments observing the evolution of low-mode-number perturbations, prescribed using a mode-6 obstacle plate, showed that the RT-driven growth was suppressed by rotation, while geometric growth remained present along with significant nonlinear distortion of the perturbations near final convergence.
Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership.
Neuropsychological assessment data from 121 participants in the Alzheimer’s Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed.
A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership.
LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
We introduce a new modelling framework to explain socio-economic differences in mortality in terms of an affluence index that combines information on individual wealth and income. The model is illustrated using data on older Danish males over the period 1985–2012 reported in the Statistics Denmark national register database. The model fits the historical mortality data well, captures their key features, generates smoothed death rates that allow us to work with a larger number of sub-groups than has previously been considered feasible, and has plausible projection properties.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
This is a case study of the U.S. pharmaceutical producer, Merck & Co. By 1940 this was one of the leading pharmaceutical producers in the United States, and the company went on to become one of the global industry leaders after World War II. It was founded in 1891 as the U.S. subsidiary of a much larger German pharmaceutical company, E. Merck of Darmstadt. The existing understanding of Merck & Co.’s history emphasizes how it was reacquired by the American branch of the Merck family after wartime sequestration, and from then onward it pursued a path of development separate from its former parent. This article revisits that history of the company and shows how the two Mercks began to cooperate and share technology and manufacturing know-how during the 1930s, something that was particularly to the advantage of Merck & Co.
Prehospital physicians balance the need to stabilize patients prior to transport, minimizing the delay to transport patients to the appropriate level of care. Literature has focused on which interventions should be performed in the prehospital environment, with airway management, specifically prehospital intubation (PHI), being a commonly discussed topic. However, few studies have sought additional factors which influence scene time or quantify the impact of mission characteristics or therapeutic interventions on scene time.
The goal of this study was to identify specific interventions, patient demographics, or mission characteristics that increase scene time and quantify their impact on scene time.
A retrospective, database model-building study was performed using the prehospital mission database of South Australian Ambulance Service (SAAS; Adelaide, South Australia) MedSTAR retrieval service from January 1, 2015 through August 31, 2016. Mission variables, including patient age, weight, gender, retrieval platform, physician type, PHI, arterial line placement, central line placement, and finger thoracostomy, were assessed for predictors of scene time.
A total of 506 missions were included in this study. Average prehospital scene time was 34 (SD = 21) minutes. Four mission variables significantly increased scene time: patient age, rotary wing transport, PHI, and arterial line placement increased scene time by 0.09 (SD = 0.08) minutes, 13.6 (SD = 3.2) minutes, 11.6 (SD = 3.8) minutes, and 34.4 (SD = 8.4) minutes, respectively.
This study identifies two mission characteristics, patient age and rotary wing transport, and two interventions, PHI and arterial line placement, which significantly increase scene time. Elderly patients are medically complex and more severely injured than younger patients, thus, may require more time to stabilize on-scene. Inherent in rotary wing operations is the time to prepare for the flight, which is shorter during ground transport. The time required to safely execute a PHI is similar to that in the literature and has remained constant over the past two years; arterial line placement took longer than envisioned. The SAAS MedSTAR has changed its clinical practice guidelines for prehospital interventions based on this study’s results. Retrieval services should similarly assess the necessity and efficiency of interventions to optimize scene time, knowing that the time required to safely execute an intervention may reach a minimum duration. Defining the scene time enables mission planning, team training, and audit review with the aim of improved patient care.
Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.