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To determine how well machine learning algorithms can classify mild cognitive impairment (MCI) subtypes and Alzheimer’s disease (AD) using features obtained from the digital Clock Drawing Test (dCDT).
dCDT protocols were administered to 163 patients diagnosed with AD(n = 59), amnestic MCI (aMCI; n = 26), combined mixed/dysexecutive MCI (mixed/dys MCI; n = 43), and patients without MCI (non-MCI; n = 35) using standard clock drawing command and copy procedures, that is, draw the face of the clock, put in all of the numbers, and set the hands for “10 after 11.” A digital pen and custom software recorded patient’s drawings. Three hundred and fifty features were evaluated for maximum information/minimum redundancy. The best subset of features was used to train classification models to determine diagnostic accuracy.
Neural network employing information theoretic feature selection approaches achieved the best 2-group classification results with 10-fold cross validation accuracies at or above 83%, that is, AD versus non-MCI = 91.42%; AD versus aMCI = 91.49%; AD versus mixed/dys MCI = 84.05%; aMCI versus mixed/dys MCI = 84.11%; aMCI versus non-MCI = 83.44%; and mixed/dys MCI versus non-MCI = 85.42%. A follow-up two-group non-MCI versus all MCI patients analysis yielded comparable results (83.69%). Two-group classification analyses were achieved with 25–125 dCDT features depending on group classification. Three- and four-group analyses yielded lower but still promising levels of classification accuracy.
Early identification of emergent neurodegenerative illness is criterial for better disease management. Applying machine learning to standard neuropsychological tests promises to be an effective first line screening method for classification of non-MCI and MCI subtypes.
The electroconvulsive therapy (ECT) is an effective treatment used for several psychiatric disorders. However, there are multiple enigmas about the mechanisms of action and factors that improve its results. Some frequent questions are if the anesthetic drug makes a difference in the time of convulsion and blood pressure.
Our principal aim is to describe the utilization of anesthetic drugs among the patients that are being treated with ECT in hospital del Mar. We also want to know the differences in the time of convulsion and systolic arterial pressure for every anesthetic drug (propofol, thiopental and etomidate).
Material and methods
We have used the database of ECT in hospital del Mar. It contains information like age, principal diagnosis, medical background and pharmacological treatment at the moment of starting ECTs; it also contains information of each individual ECT session as basal, 2 and 5 minutes arterial pressure; the anesthetic drug used, and convulsion duration.
We made an analysis of general conditions of the population, the differences of convulsion time and arterial pressure between the three anesthetic drugs.
Propofol was used in 1140 sessions, thiopental in 61 sessions and etomidate in 54 sessions. The differences in the means of convulsion times between propofol and etomidate are statistically significant (“P” value < 0.05). Etomidate or thiopental increases the difference of arterial pressure more than propofol.
Further research about the factors that improve convulsion duration and minimize adverse effects on blood pressure is needed.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices.
All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS.
A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270–639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome.
EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples.
Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons.
FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms.
This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.
Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom.
We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians.
Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window.
Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice.
Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume.
Jak et al. (2009) (The American Journal of Geriatric Psychiatry, 17, 368–375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer’s Disease, 47(1), 231–242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z-scores.
Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance.
Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests.
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 aim of this study is to investigate the impact of anatomical changes in prostate cancer patients on the target coverage when using 6 MV beams-VMAT therapy and to propose strategies that allow us to evaluate the dose or correct it by normalization without having to perform a new simulation.
Methods and materials:
Ten patients of high-risk prostate cancer were chosen for the study. All test plans were delivered using the same isocenter and monitor units as the original plan and compared against the original unedited plan. The expansion and contraction of body contours due to size changes was mimicked by increasing and decreasing the body contour with depths of −2, −1·5, …, 1·5, 2 cm, in the anterior, and both lateral directions of the patient. A total of 90 plans were evaluated, 9 for each patient. Dose-volume histogram statistics were extracted from each plan and normalized to prescription dose.
Weight changes resulted in considerable dose modifications to the target and critical structures. Plans were found to be varied with 2·9% ± 0·3% per cm SSD change for VMAT treatment with a correlation index close to one. Therefore, doses variations were linear to the changes of depth. Gamma index evaluation was performed for the 10 renormalized plans. All of them passed criteria of 3%/3 mm in at least 98.2% of points. Eight of them passed criteria in 99% points. Gamma index 4%/4 mm passed 100% points in all patients for the chosen region of interest.
The dosimetry estimation presented in this study shows important data for the radiation oncology staff to justify whether a CT rescan is necessary or not when a patient experiences weight changes during treatment. Based on the results of our study, discrepancies between real dose and planned dose were >5% for 1·7 cm of difference in external contour in the anterior and both lateral directions of the patient.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
The objective of this study was to prospectively validate the “Brief Developmental Assessment”, which is a new early recognition tool for neurodevelopmental abnormalities in children with heart disease that was developed for use by cardiac teams.
This was a prospective validation study among a representative sample of 960 pre-school children with heart disease from three United Kingdom tertiary cardiac centres who were analysed grouped into five separate age bands.
The “Brief Developmental Assessment” was successfully validated in the older four age bands, but not in the youngest representing infants under the age of 4 months, as pre-set validation thresholds were met – lower 95% confidence limit for the correlation coefficient above 0.75 – in terms of agreement of scores between two raters and with an external measure the “Mullen Scales of Early Learning”. On the basis of American Association of Pediatrics Guidelines, which state that the sensitivity and specificity of a developmental screening tool should fall between 70 and 80%, “Brief Developmental Assessment” outcome of Red meets this threshold for detection of Mullen scores >2 standard deviations below the mean.
The “Brief Developmental Assessment” may be used to improve the quality of assessment of children with heart disease. This will require a training package for users and a guide to action for abnormal results. Further research is needed to determine how best to deploy the “Brief Developmental Assessment” at different time points in children with heart disease and to determine the management strategy in infants younger than 4 months old.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
The results of the first molecular phylogenetic study of Pseudephebe are presented; a three-locus phylogeny. The genus is confirmed as monophyletic within the alectorioid clade of Parmeliaceae. Two major clades were recovered, which can be assigned to the two traditional taxa, P. minuscula and P. pubescens, with modifications of the species delimitation, especially the variable P. minuscula. These species are cryptic and cannot be confidently distinguished morphologically due to phenotypic convergence. Therefore, the use of P. pubescens aggr. is recommended for samples not molecularly analyzed. Contrary to previous studies, specimens of both species might have indistinct pseudocyphellae and also contain lichen substances; norstictic acid was detected in c. 60% of specimens tested. An SSU 1516 Group I intron is usually present in P. minuscula but always absent in P. pubescens. The species-level nomenclature is summarized and sequenced reference specimens (RefSpec) for both Pseudephebe species are selected. Sequences from Bryoria mariensis established that this name was a synonym of P. minuscula.
There is heated debate over the wisdom and effect of secrecy in international negotiations. This debate has become central to the process of foreign investment arbitration because parties to disputes nearly always can choose to hide arbitral outcomes from public view. Working with a new database of disputes at the world's largest investor-state arbitral institution, the World Bank's International Centre for Settlement of Investment Disputes, the authors examine the incentives of firms and governments to keep the details of their disputes secret. The authors argue that secrecy in the context of investment arbitration works like a flexibility-enhancing device, similar to the way escape clauses function in the context of international trade. To attract and preserve investment, governments make contractual and treaty-based promises to submit to binding arbitration in the event of a dispute. They may prefer secrecy in cases when they are under strong political pressure to adopt policies that violate international legal norms designed to protect investor interests. Investors favor secrecy when managing politically sensitive disputes over assets they will continue to own and manage in host countries long after the particular dispute has passed. Although governments prefer secrecy to help facilitate politically difficult bargaining, secrecy diminishes one of the central purposes of arbitration: to allow governments to signal publicly their general commitment to investor-friendly policies. Understanding the incentives for keeping the details of dispute resolution secret may help future scholars explain more accurately the observed patterns of wins and losses from investor-state arbitration as well as patterns of investment.
Transition metal dichalcogenides such as WS2 show exciting promise in electronic and optoelectronic applications. Significant variations in the transport, Raman, and photoluminescence (PL) can be found in the literature, yet it is rarely addressed why this is. In this report, Raman and PL of monolayered WS2 produced via different methods are studied and distinct features that indicate the degree of crystallinity of the material are observed. While the intensity of the LA(M) Raman mode is found to be a useful indicator to assess the crystallinity, PL is drastically more sensitive to the quality of the material than Raman spectroscopy. We also show that even exfoliated crystals, which are usually regarded as the most pristine material, can contain large amounts of defects that would not be apparent without Raman and PL measurements. These findings can be applied to the understanding of other two-dimensional heterostructured systems.
The literature on faction suggests that patrons in the party may recruit faction members on the basis of a broad range of shared traits and experience. Some scholars argue reasonably that with increasing specialization of officials, factions are increasingly dominated by those with shared work experience in a set of bureaucracies. Although this trend may be true in general, senior leaders may still recruit those with whom they share birth place and school ties into their factions. To investigate this, we first derive four reasonable ways of measuring factional ties as suggested by the literature. We then explore the factional recruitment strategy pursued by each reform-era (1978–present) party secretary generals of the CCP by evaluating the measures of factional ties which predicted their clients’ promotions to full Central Committee membership. Our results show that Hu Yaobang, Jiang Zemin, and Xi Jinping pursued broadly based factional recruitment strategies, while Hu Jintao recruited faction members mainly from work colleagues. We further uncover signs that the party institutions may allow deposed secretary generals some measure of influence over promotions even after their political demise. At the same time, strict retirement rules on lower level officials gave rise to a cohort effect that gave the general secretary greater influence over the promotion of alternate Central Committee members to the full Central Committee during their first term than in subsequent terms.
The history of leadership change in the Chinese Communist Party (CCP) exemplifies Pareto's notion of circulation of the elite. To analyze it we have compiled a partially ranked dataset of members and alternates of the Politburo Standing Committee, Politburo, and Central Committee for the 1st through 18th National Party Congresses. Quantitative studies of leadership change in the CCP have typically focused on the fraction of new members in each political body from one Party Congress to the next, but the existence of partially ranked data calls for a more subtle quantification of leadership change. Thus, we define a new family of metrics which consider change within each political body, the magnitude of such change, and the importance of each change to CCP structure and policy. We use two of these metrics to compute the distances between each pair of successive, partially-ranked leadership lists in our dataset. Our results capture important political developments from the irregular leadership change of the early years to the subsequent transformation of the CCP into a more institutionalized polity. This metric-based analysis also supplements our understanding of anomalous leadership transitions, intra-Party dynamics, and systemic change in the CCP.