Background: Acute ischemic stroke is one of the leading causes of disability and mortality globally, with increasing incidence in Africa, as the continent is already burdened with infectious diseases. Rapid diagnosis and efficient treatment are crucial, as even a slight delay to reperfuse the brain significantly affects the recovery outcome. Neuroimaging is vital for optimal care and thrombolytic or endovascular therapy in specialised stroke care units. This review aims to discuss the burden of acute ischemic stroke in Africa and how healthcare systems have tried to reduce the incidence and improve outcomes for the disease. Methodology: Data was collected from online databases and medical journal published on PubMed, Ovid MEDLINE, ScienceDirect and Embase bibliographical data. All articles related to acute ischemic stroke in Africa were considered. Results: The medical care for acute ischemic stroke in Africa is far from optimal with little adherence to recommended protocols. There is a lack of public awareness of the disease, imaging infrastructure, personnel, stroke care units and recovery facilities, due to poor funding. Poor knowledge of stroke signs and symptoms results in delay in treatment and poor prognosis. Conclusion: We urge African leaders and private entities to invest in stroke care by building appropriate infrastructures, providing medical equipments, implementing guidelines, and sustainable follow-up systems. Telehealth is a suggested strategy to mitigate the scarcity of health personnel, and international and national efforts to increase treatment affordability should be doubled. Further extensive research on the impact of acute ischemic stroke on the African continent population is encouraged.
Background: Previous studies demonstrated that when the violence-exposed child becomes a mother and interacts with her own child during early sensitive periods for social-emotional development, she may have difficulties providing sensitive responsiveness to the child's emotional communication. Such difficulties place the child's development of emotional comprehension (EC) and related self-regulation at risk. The aim of this study was to examine how mothers' interpersonal violence-related posttraumatic disorder (IPV-PTSD) would affect their children's EC and their own ability to predict their children's EC. We also investigated how mothers' predictive ability would correlate with child psychopathology. Methods: Sixty-one mother-child dyads (36 with IPV-PTSD) participated in this study. Children's (mean age = 7.0 years, SD = 1.1) EC was assessed with the Test of Emotion Comprehension (child TEC) and their psychopathology as reported by the mother was assessed with the Child Behaviour Checklist (CBCL) and as evaluated by a clinician using selected modules of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Mothers were measured for IPV-PTSD with the Clinician Administered PTSD Scale (CAPS) and for their capacity to predict their child's emotional comprehension (mother-responding-as-child TEC; mTEC). Results: We found no significant between-group differences in children's level of EC. Maternal PTSD was associated with lower scores on the mTEC, however. Reduced maternal scores on the mTEC were significantly associated with maternal report of increased aggressive child behaviour and with depression symptoms on the K-SADS. Further, scores on the mTEC interacted with maternal report of child aggression on child oppositional defiant disorder (ODD) symptoms on the K-SADS. Conclusion: These findings support that improving maternal emotional comprehension may help reduce child risk for psychiatric morbidity in this population.
Background: PCL-5 is a self-report measure consisting of 20 items that are used to assess the symptoms of Post-Traumatic Stress Disorder (PTSD) according to the DSM-5. Objective: This study evaluated the factor structure of the Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) in people with serious mental illness. Method: The sample in Study 1 included 536 participants with serious mental illness who were receiving supported employment services through community mental health agencies or supported housing programmes. Confirmatory factor analysis assessed the fit of six different models of PTSD. Results: Results indicated that Armour's Hybrid 7-factor model composed of re-experiencing, avoidance, dysphoria, dysphoric arousal, anxious arousal, negative affect, anhedonia, and externalizing behaviours demonstrated the best fit. Study 2 found support for convergent validity for PCL-5 among 132 participants who met criteria for PTSD. Conclusion: Findings provide support for the psychometric properties of the PCL-5 and the conceptualization of the 7-factor hybrid model and the 4-factor DSM-5 model of PTSD among persons living with serious mental illness.
Recent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD.
Background Smoking cessation is the most effective means of slowing the decline of lung function associated with chronic obstructive pulmonary disease (COPD). While effective smoking cessation treatments are available, they are underutilized and nearly half of people with COPD continue to smoke. By addressing both nicotine and behavioral dependence, electronic cigarettes (EC) could help people with COPD reduce the harm of combustible cigarettes (CC) through reductions in number of Cigarettes per Day (CPD) or quitting CC completely. The purpose of this pilot study is to identify barriers and facilitators to the use of and assess the preliminary effectiveness of EC as a harm reduction strategy among people with COPD. Methods In an open-label two-arm randomized controlled trial pilot study, 60 patients identified as smokers with a COPD diagnosis via electronic health records from a large urban health center are randomized in a 1:1 ratio to either standard care [counseling + nicotine replacement therapy (NRT)] or counseling + EC. The NRT arm will receive nicotine patches and nicotine lozenges for 12 weeks. The EC arm will receive EC for 12 weeks. Both cohorts will receive counseling from a licensed mental health counselor. Using ecological momentary assessment, participants will report their use of CC in both arms and EC use in the EC arm daily via text message. Primary outcomes will be feasibility and acceptability of intervention, and secondary outcomes will be reduction in CPD and change in COPD symptoms as measured by COPD Assessment Tool (CAT) score at 12-weeks. EC displacement of CC. To explore attitudes towards the use of EC as a harm-reduction strategy for patients with COPD, interviews will be performed with a sample of participants from both study arms. Discussion Despite decades of availability of smoking cessation medications, nearly half of people with COPD still smoke. This study aims to address the unmet need for feasible and effective strategies for reducing CC use among those with COPD, which has the potential to significantly improve the health of people with COPD who smoke. Trial Registration ClinicalTrials.gov Identifier: NCT04465318.
The importance of integrating biomarkers into the TNM staging has been emphasized in the 8 th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8 th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.
The path to a sustainable management of the urban water cycle requires the assessment of both operational and quality-adjusted efficiency in a unified manner. This can be done by the use of non-radial Data Envelopment Analysis models. This study used Range Adjusted Measure models to evaluate the operational, quality-adjusted, and operational & quality-adjusted efficiency (O&QAE) scores of the Chilean water industry including water leakage and unplanned interruptions as undesirable outputs. It was found that on average water utilities presented large O&QAE scores over time. The mean O&QAE score was 0.964 which means that water utilities could further reduce costs and undesirable outputs by 3.6% on average, while trying to expand the scale of operation. This finding suggests that excellent quality-adjusted efficiency at an efficient expenditure could be feasible. It was also evidenced that customer density, mixed water resources, and ownership influenced the O&QAE of Chilean water companies.
Introduction DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos. Results We conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10 ⁻⁷ in the combined analyses from Puerto Ricans and Mexican Americans: cg06035600 ( MAP3K6 , p = 6.13 × 10 ⁻⁸ ) showed significant association with pre-bronchodilator Tiffeneau–Pinelli index, the probes cg00914963 ( TBC1D16 , p = 1.04 × 10 ⁻⁷ ), cg16405908 ( MRGPRE , p = 2.05 × 10 ⁻⁸ ) , and cg07428101 ( MUC2 , p = 5.02 × 10 ⁻⁹ ) were associated with post-bronchodilator forced vital capacity (FVC), and cg20515679 ( KCNJ6 ) with post-bronchodilator Tiffeneau–Pinelli index ( p = 1.13 × 10 ⁻⁸ ). However, these markers did not show significant associations in publicly available data from Europeans ( p > 0.05). A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. Additionally, two differentially methylated regions in REXOC and AURKC were associated with pre-bronchodilator Tiffeneau–Pinelli index (adjusted p < 0.05) in Puerto Ricans and Mexican Americans. Moreover, we replicated some of the previous differentially methylated signals associated with lung function in non-Latino populations. Conclusions We replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups.
The discovery of two-dimensional (2D) magnetic van der Waals (vdW) materials has flourished an endeavor for fundamental problems as well as potential applications in computing, sensing and storage technologies. Of particular interest are antiferromagnets, which due to their intrinsic exchange coupling show several advantages in relation to ferromagnets such as robustness against external magnetic perturbations. Here we show that, despite of this cornerstone, the magnetic domains of recently discovered 2D vdW MnPS 3 antiferromagnet can be controlled via magnetic fields and electric currents. We achieve ultrafast domain-wall dynamics with velocities up to ~3000 m s ⁻¹ within a relativistic kinematic. Lorentz contraction and emission of spin-waves in the terahertz gap are observed with dependence on the edge termination of the layers. Our results indicate that the implementation of 2D antiferromagnets in real applications can be further controlled through edge engineering which sets functional characteristics for ultrathin device platforms with relativistic features.
Background: Antisocial personality disorder (ASPD) incurs a high cost to society due to the high risk of violent and nonviolent offenses associated with this personality disorder, thus making the examination of the etiology and the onset of ASPD an important public health concern. Method: The present study consisted of five waves of data collection of the Harlem Longitudinal Development Study (N = 674). In the Cox proportional hazard model, latent multiple substance use trajectories from mid-adolescence to emerging adulthood (mean age 14 to mean age 24) were used as a predictor for the onset of ASPD during emerging adulthood to the mid-thirties (mean age 24 to mean age 36). The control variables were gender, ethnicity, problem behaviors, and victimization. Results: In the multiple Cox proportional hazard model, the high (HR = 2.74, p < 0.001) and the increasing frequency of (HR = 2.55, p < 0.001) use on alcohol, cigarette, and cannabis latent trajectory groups were associated with an increased hazard of ASPD onset as compared with the no or low frequency of use on alcohol, cigarette, and cannabis latent trajectory group after controlling for demographic factors and earlier problem behaviors as well as victimization. Conclusions: The implications of this study for the prediction of adult ASPD onset time may focus on the early use of alcohol, cigarette, and cannabis from mid adolescence to emerging adulthood.
Silicon (Si) fertiliser can improve rice (Oryza sativa) tolerance to salinity. The rate of Si uptake and its associated benefits are known to differ between plant genotypes, but, to date, little research has been done on how the benefits, and hence the economic feasibility, of Si fertilisation varies between cultivars. In this study, a range of rice cultivars was grown both hydroponically and in soil, at different levels of Si and NaCl, to determine cultivar variation in the response to Si. There was significant variation in the effect of Si, such that Si alleviated salt-induced growth inhibition in some cultivars, while others were unaffected, or even negatively impacted. Thus, when assessing the benefits of Si supplementation in alleviating salt stress, it is essential to collect cultivar-specific data, including yield, since changes in biomass were not always correlated with those seen for yield. Root Si content was found to be more important than shoot Si in protecting rice against salinity stress, with a root Si level of 0.5–0.9% determined as having maximum stress alleviation by Si. A cost–benefit analysis indicated that Si fertilisation is beneficial in mild stress, high-yield conditions but is not cost-effective in low-yield production systems.
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13024-021-00438-3.
Mendelian randomization (MR) is a term that applies to the use of genetic variation to address causal questions about how modifiable exposures influence different outcomes. The principles of MR are based on Mendel’s laws of inheritance and instrumental variable estimation methods, which enable the inference of causal effects in the presence of unobserved confounding. In this Primer, we outline the principles of MR, the instrumental variable conditions underlying MR estimation and some of the methods used for estimation. We go on to discuss how the assumptions underlying an MR study can be assessed and describe methods of estimation that are robust to certain violations of these assumptions. We give examples of a range of studies in which MR has been applied, the limitations of current methods of analysis and the outlook for MR in the future. The differences between the assumptions required for MR analysis and other forms of epidemiological studies means that MR can be used as part of a triangulation across multiple sources of evidence for causal inference. Mendelian randomization is a technique for using genetic variation to examine the causal effect of a modifiable exposure on an outcome such as disease status. This Primer by Sanderson et al. explains the concepts of and the conditions required for Mendelian randomization analysis, describes key examples of its application and looks towards applying the technique to growing genomic datasets.
An increasing prevalence of data-sharing models, aimed at making individual participant data (IPD) from clinical trials widely available, should facilitate the conduct of systematic reviews and meta-analyses based on IPD. We have assessed these different data-sharing approaches, from the perspective of experienced IPD reviewers, to examine their utility for conducting systematic reviews based on IPD, and to highlight any challenges. We present an overview of the range of different models, including the traditional, single question approach, topic-based repositories, and the newer generic data platforms, and show that there are benefits and drawbacks to each. In particular, not all of the new models allow researchers to fully realise the well-documented advantages of using IPD for meta-analysis, and we offer potential solutions that can help improve both data quantity and utility. However, to achieve the “nirvana” of an ideal clinical data sharing environment, both for IPD meta-analysis and other secondary research purposes, we propose that data providers, data requestors, funders, and platforms need to adopt a more joined-up and standardised approach.
Background The relationship between anatomical variations in circle of Willis and brain infarction is controversial. The purpose of this study was to evaluate the relationship between anatomical variations in posterior portion of the circle of Willis assessed by MR angiography (MRA) and ischemic infarction in different brain territories. Methods This cross-sectional study was conducted on consecutive patients who underwent brain MRI and MRA for suspected cerebrovascular accident. The frequency of anatomical variations including persistent fetal origin of posterior cerebral artery (fPCA) and hypoplastic/aplastic posterior communicating artery (PCoA) and their association with infarction in different intracranial vascular territories was assessed. Results In total, 298 patients (155 male/143 female with mean age ± SD of 57 ± 15) were enrolled in the study and categorized into two groups with infarction ( n = 142) and without infarction ( n = 156). Sixty-three patients (21/1%) had fPCA and 231 (77.5%) had PCoA hypoplasia/aplasia. No significant correlation was identified between fPCA or PCoA hypoplasia/aplasia and presence of infarction. However, regarding the territories involved by infarction, the frequency of thalamus infarction was higher in subgroup with PCoA hypoplasia/aplasia, 17/101 (16.8%) compared to 1/41(2.4%) in the subgroup without ipsilateral PCoA hypoplasia/aplasia ( p = 0.024). In two subgroups with and without ipsilateral fPCA variation, frequency of infarction in brain territories was not different significantly. Conclusions In patients with brain infarction, aplastic/hypoplastic ipsilateral PCoA is associated with higher incidence of thalamic territory infarction.
The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.
Background Traditional introductory point-of-care ultrasound (POCUS) courses are resource intensive, typically requiring 2–3 days at a remote site, consisting of lectures and hands-on components. Social distancing requirements resulting from the COVID-19 pandemic led us to create a novel hybrid course curriculum consisting of virtual and in-person components. Methods Faculty, chief residents, fellows and advanced practice providers (APPs) in the Department of Medicine were invited to participate in the hybrid curriculum. The course structure included 4 modules of recorded lectures, quizzes, online image interpretation sessions, online case discussions, and hands-on sessions at the bedside of course participant’s patients. The components of the course were delivered over approximately 8 months. Those participants who completed a minimum of 3 modules over the year were invited for final assessments. Results from the hybrid curriculum cohort were compared to the year-end data from a prior traditional in-person cohort. Results Participant knowledge scores were not different between traditional ( n = 19) and hybrid ( n = 24) groups (81% and 84%, respectively, P = 0.9). There was no change in POCUS skills as measured by the hands-on test from both groups at end-of-course (76% and 76%, respectively, P = 0.93). Confidence ratings were similar across groups from 2.73 traditional to 3.0 hybrid (out of possible 4, P = 0.46). Participants rated the course highly, with an average overall rating of 4.6 out 5. Conclusions A hybrid virtual and in-person POCUS course was highly rated and as successful as a traditional course in improving learner knowledge, hands-on skill and confidence at 8 months after course initiation. These results support expanding virtual elements of POCUS educational curricula.
Background Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD). Methods Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019. Results A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients. Conclusions The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.
Accurate, unbiased and concise synthesis of available evidence following clear methodology and transparent reporting is necessary to support effective environmental policy and management decisions. Without this, less reliable and/or less objective reviews of evidence could inform decision making, leading to ineffective, resource wasteful interventions with potential for unintended consequences. We evaluated the reliability of over 1000 evidence syntheses (reviews and overviews) published between 2018 and 2020 that provide evidence on the impacts of human activities or effectiveness of interventions relevant to environmental management. The syntheses are drawn from the Collaboration for Environmental Evidence Database of Evidence Reviews (CEEDER), an online, freely available evidence service for evidence users that assesses the reliability of evidence syntheses using a series of published criteria. We found that the majority of syntheses have problems with transparency, replicability and potential for bias. Overall, our results suggest that most recently published evidence syntheses are of low reliability to inform decision making. Reviews that followed guidance and reporting standards for evidence synthesis had improved assessment ratings, but there remains substantial variation in the standard of reviews amongst even these. Furthermore, the term ‘systematic review’, which implies conformity with a methodological standard, was frequently misused. A major objective of the CEEDER project is to improve the reliability of the global body of environmental evidence reviews. To this end we outline freely available online resources to help improve review conduct and reporting. We call on authors, editors and peer reviewers to use these resources to ensure more reliable syntheses in the future.
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