To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Innovation Concept: In Sudbury, ON 44% of out-of-hospital cardiac arrest (OHCA) patients receive bystander CPR (bCPR), and only 4.7% survive cardiac arrest. The Northern City of Heroes (NCH) community initiative was launched in April 2019 with a goal of improving survival from OHCA through hands-only bCPR in the municipality. One NCH initiative is an interactive exhibit at Science North, a science centre in Sudbury that hosts 250,000 visitors annually. The exhibit employs simulation trainers for CPR, accompanying signage and interactive elements. The goals of the exhibit are to activate bCPR, change and measure behaviours through exhibit interactions on how to deliver excellent CPR, and improve survival rates in OHCA patients. Methods: Data is being collected from 3000 visitors using self-reported surveying via SurveyGizmo to assess likelihood of performing bCPR, pre and post interacting with the exhibit. Visitor behaviour will be examined at the exhibit using video-recorded interactions and coding those behaviours using BORIS software. Behavioural data will be analyzed using the Visitor Engagement Framework (VEF) where initiation, transition and breakthrough learning-behaviours are coded and an exhibit Visitor Engagement Profile (VEP) is created. The VEF and VEP are tools used in informal learning settings to assess exhibit impacts on learning. Curriculum, Tool, or Material: The use of an easily-apprehendable, hands-on exhibit tool located in a public setting, such as a science centre, creates a platform for engaging large and diverse public audiences. This type of bCPR exhibitry has not been implemented in other similar environments. The informal learning setting allows the science centre staff to engage in personalized interactions that can solidify the quality of learning and confidence in employing the new skills developed. Conclusion: The NCH exhibit and new strategies for embedding informal curriculum are powerful tools to reach diverse audiences, build knowledge and skills, and have a measurable impact on bCPR and OHCA survival rates. Data is being captured and tracked by Health Sciences North around the City of Greater Sudbury's bCPR and OHCA survival rates to monitor long-term impacts of the NCH community initiatives. Limitations of the study may be found in the focused demographics as well as the nature of self-reported learning. Future research directions include broader geographical surveying to assess improvements in community response to OHCA as a direct result of an interactive bCPR exhibitry.
Little is known about emotional quality-of-life in paediatric heart disease in low- and middle-income countries where the prevalence of uncorrected lesions is high. Research on emotional quality-of-life and its predictors in these settings is key to planning interventions.
Ten-year retrospective cross-sectional study of children aged 6–17 years with uncorrected congenital or acquired heart disease in 12 low- and middle-income countries was conducted. Emotional functioning score of the PedsQL TM 4.0 generic core scale and data on patient-reported limitation in sports participation were collected via in-person interview and analysed using regression analyses.
Ninety-four children reported mean emotional functioning scores of 71.94 (SD 25.32) [95% CI 66.75–77.13] with lower scores independently associated with having a parent with a chronic illness or who had died (p = 0.005), having less than three siblings (p = 0.007), and reporting a subjective limitation in carrying an item equivalent to a 4 lb load (p = 0.021). Patient-reported limitation in sports participation at least “sometimes” was present in 69% and was independently associated with experiencing symptoms at least once a month (p < 0.001).
Some of the factors which were associated with better emotional quality-of-life were similar to those identified in previous studies in patients with corrected defects. Patient-reported limitation in sports participation is common. In addition to corrective surgery and exercise, numerous other interventions which are practicable during surgical missions might improve emotional quality-of-life.
The main objective of “Lifebrain” is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.
As mental healthcare expands to smartphone apps and other technologies that may offer therapeutic interventions without a therapist involved, it is important to assess the impact of non-traditional therapeutic relationships.
To determine if there were any meaningful data regarding the digital therapeutic alliance in smartphone interventions for serious mental illnesses.
A literature search was conducted in four databases (PubMed, PsycINFO, Embase and Web of Science).
There were five studies that discuss the therapeutic alliance when a mobile application intervention is involved in therapy. However, in none of the studies was the digital therapeutic alliance the primary outcome. The studies looked at different mental health conditions, had different duration of technology use and used different methods for assessing the therapeutic alliance.
Assessing and optimising the digital therapeutic alliance holds the potential to make tools such as smartphone apps more effective and improve adherence to their use. However, the heterogeneous nature of the five studies we identified make it challenging to draw conclusions at this time. A measure is required to evaluate the digital therapeutic alliance.
We have been intensely monitoring photometric variability in proto-planetary nebulae (PPNe) over the past 25 years and radial velocity variability over the past ten years. Pulsational variability has been obvious, in both the light and velocity, although the resulting curves are complex, with multiple periods and varying amplitudes. Observed periods range from 25 to 160 days, and the periods and amplitudes reveal evolutionary trends. We will present our observational results to date for approximately 30 PPNe, and discuss these results, including the search for period changes that might help constrain post-AGB evolutionary timescales.
Glioblastoma is inherently resistant to radiation and drug treatments. This is mediated by the most common forms of cell death are often actively inhibited. Identifying and exploiting alternative cell death pathways are essential to overcoming or bypassing drug resistance. Ferroptosis, a newly described, morphologically and biochemically distinct, cell death mechanism is characterized by iron-dependent cellular accumulation of reactive oxygen species. The combination of siramesine, a lysosome disruptor, and lapatinib, a dual tyrosine kinase inhibitor (TKI), synergistically induced death in glioma cancer cells. This cell death had characteristics of ferroptosis: it was blocked by the ferroptosis inhibitor ferrostatin-1 and the iron chelator deferoxamine. In addition, the amount of ROS and lipid peroxidation were increased in glioma cells. Iron transport protein remained unchanged but reactive iron levels increased. One target for kinase inhibitors is protein bisulfate isomerase (PDI). Knockdown of PDI in combination with siramesine increased cell death that was blocked by ferrostatin-1. Taken together, drug combinations that alter reactive iron and ROS levels might induce ferroptosis and overcome drug resistance in glioma cells.
Decades of research have investigated the impact of clinical depression on memory, which has revealed biases and in some cases impairments. However, little is understood about the effects of subclinical symptoms of depression on memory performance in the general population.
Here we report the effects of symptoms of depression on memory problems in a large population-derived cohort (N = 2544), 87% of whom reported at least one symptom of depression. Specifically, we investigate the impact of depressive symptoms on subjective memory complaints, objective memory performance on a standard neuropsychological task and, in a subsample (n = 288), objective memory in affective contexts.
There was a dissociation between subjective and objective memory performance, with depressive symptoms showing a robust relationship with self-reports of memory complaints, even after adjusting for age, sex, general cognitive ability and symptoms of anxiety, but not with performance on the standardised measure of verbal memory. Contrary to our expectations, hippocampal volume (assessed in a subsample, n = 592) did not account for significant variance in subjective memory, objective memory or depressive symptoms. Nonetheless, depressive symptoms were related to poorer memory for pictures presented in negative contexts, even after adjusting for memory for pictures in neutral contexts.
Thus the symptoms of depression, associated with subjective memory complaints, appear better assessed by memory performance in affective contexts, rather than standardised memory measures. We discuss the implications of these findings for understanding the impact of depressive symptoms on memory functioning in the general population.
Several pathogens have been associated with increased cardiovascular disease (CVD) risk. Whether this occurs with Mycobacterium tuberculosis infection is unclear. We assessed if tuberculosis disease increased the risk of acute myocardial infarction (AMI). We identified patients with tuberculosis index claims from a large de-identified database of ~15 million adults enrolled in a U.S. commercial insurance policy between 2008 and 2010. Tuberculosis patients were 1:1 matched to patients without tuberculosis claims using propensity scores. We compared the occurrence of index AMI claims between the tuberculosis and non-tuberculosis cohorts using Kaplan–Meier curves and Cox Proportional Hazard models. Data on 2026 patients with tuberculosis and 2026 propensity-matched patients without tuberculosis were included. AMI was more frequent in the tuberculosis cohort compared with the non-tuberculosis cohort, 67 (3·3%) vs. 32 (1·6%) AMI cases, respectively, P < 0·01. Tuberculosis was associated with an increased risk of AMI (adjusted hazard ratio (HR) 1·98, 95% confidence intervals (CI) 1·3–3·0). The results were similar when the analysis was restricted to pulmonary tuberculosis (adjusted HR 2·43, 95% CI 1·5–4·1). Tuberculosis was associated with an increased risk of AMI. CVD risk assessment should be considered in tuberculosis patients. Mechanistic studies of tuberculosis and CVD are warranted.
Mcl-1 is an anti-apoptotic Bcl-2 family member that is often over-expressed in the malignant brain tumour glioblastoma (GBM). It has been previously shown that epidermal growth factor receptors (EGFR) up-regulate Mcl-1 expression contributing to a cell survival response. Hypoxia is a poor prognostic marker in glioblastoma despite the fact that hypoxic regions have areas of necrosis. Hypoxic regions of GBM also highly express the pro-cell death Bcl-2 family member BNIP3, yet when BNIP3 is over-expressed in glioma cells, it induces cell death. The reasons for this discrepancy are unclear. METHODS: Using malignant glioma cell lines +/- hypoxia, gain and/or loss of function assays of BNIP3 or Mcl-1 were performed. BNIP3 and MCL-1 expression was assessed in GBM tumours from adult patients and human gliomas grown as xenografts in immunocompromised mice. RESULTS: Mcl-1 expression is reduced under hypoxia due to degradation by the E3 ligase FBW7 leading to increased hypoxia-induced cell death. This cell death is augmented by EGFR activation leading to increased Mcl-1 expression under hypoxia. Conversely, BNIP3 is over-expressed in hypoxia at times when Mcl-1 expression is decreased. Knocking down BNIP3 expression reduces hypoxia cell death and Mcl-1 expression effectively blocks BNIP3-induced cell death. Of significance, BNIP3 and Mcl-1 are co-localized under hypoxia in glioma cells, GBM tumours and in xenograft glioma tumours expressing mutant EGFR (EGFRvIII). CONCLUSION: These results support that Mcl-1 can block the ability of BNIP3 to induce cell death under hypoxia in GBM tumours