How to Undertake a Clinically Relevant Systematic Review in a Rapidly Evolving Field: Magnetic Resonance Angiography

Objectives: The aim was to determine which generations of the evolving technology of magnetic resonance angiography (MRA) are currently of clinical relevance in two clinical applications. Our purpose was to plan a systematic review that would be valuable both to purchasers driven by cost-effectiveness and to practicing clinicians. Methods: Information was gathered from a search of major bibliographic databases, from a short questionnaire sent to 500 U.K. vascular radiologists and vascular surgeons, and from local clinical The authors thank A. Jackson and all those who completed a questionnaire. This work was carried out with the financial support of the Secretary of State for Health under the NHS Health Technology Assessment Programme, project 97/13/04. The views and opinions expressed do not necessarily reflect those of the Secretary of State for Health. In part, this work was undertaken by the Leeds Teaching Hospitals NHS Trust, which received funding from the NHS Executive. The views expressed in this publication are those of the authors and not necessarily those of the NHS Executive.experts. We asked which of the MRA techniques were currently used and, assuming availability, what would be their technique of choice. Results: There were 206 published articles that satisfied preliminary inclusion criteria: 69 discussed 2D time of flight (TOF); 47, 3D TOF; and 38, contrast-enhanced techniques. There were 162 questionnaires returned (60 radiologists, 102 surgeons). Of the total respondents, 77/162 (48%) used MRA in the assessment of carotid artery stenosis; 47/77 (61%) used 2D TOF; 32/77 (42%), 3D TOF; and 26/77 (34%), contrast-enhanced techniques. Thirty-five of 162 (22%) respondents used MRA in the assessment of peripheral vascular disease (PVD); 15/35 (43%) used 2D TOF, 4/35 (11%) used 3D TOF, and 22/35 (63%) used contrast-enhanced techniques. For those wishing to use MRA, contrast-enhanced techniques were the method of choice. Conclusions: The TOF methods that represent earlier generations of the technology remain clinically relevant, and will therefore be included in our systematic review. To ensure complete and relevant coverage in reviews of other evolving technologies, it would be advisable to obtain data for guidance in a similar way

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review

Objective To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. Design Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. Main outcome measures Performance characteristics of diagnostic test. Results 126 potentially relevant articles were identified, but many articles failed to examine die performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. Conclusions Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes

Quality of parental emotional care and calculated risk for coronary heart disease

Objective: To evaluate associations between perceived quality of parental emotional care and calculated 10-year risk for coronary heart disease (CHD). Little is understood about the role of parental emotional care in contributing to the risk for CHD. Methods: The study sample was composed of 267 participants from the New England Family Study. Quality of parental emotional care was measured, using a validated short version of the Parental Bonding Instrument (PBI) as the average care scores for both parents (range = 0-12), with higher scores indicating greater care. Ten-year CHD risk was calculated, using the validated Framingham Risk Algorithm that incorporates the following prevalent CHD risk factors: age, sex, diabetes, smoking, total cholesterol, high-density lipoprotein cholesterol, and blood pressure. Multiple linear regression assessed associations of PBI with calculated CHD risk after adjusting for childhood socioeconomic status, depressive symptomatology, educational attainment, and body mass index. Results: Among females, a 1-unit increase in the parental emotional care score resulted in a 4.6% (p =.004) decrease in the 10-year CHD risk score, after adjusting for covariates. There was no association between parental emotional care score and calculated CHD risk score in males (p =.22). Conclusion: Quality of parental emotional care was inversely associated with calculated 10-year CHD risk in females, and not males. Although the gender differences need further investigation and these findings require replication, these results suggest that the early childhood psychosocial environment may confer risk for CHD in adulthood

DCC gene network in the prefrontal cortex is associated with total brain volume in childhood

BACKGROUND: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. METHODS: We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual's genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. RESULTS: Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. LIMITATIONS: The relatively small sample size and age differences between the main and replication cohorts were limitations. CONCLUSION: Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment

Social reward among juvenile mice

Mammalian social relationships, such as mother–offspring attachments and pair bonds, can directly affect reproductive output. However, conspecifics approach one another in a comparatively broad range of contexts, so conceivably there are motivations for social congregation other than those underlying reproduction, parental care or territoriality. Here, we show that reward mediated by social contact is a fundamental aspect of juvenile mouse sociality. Employing a novel social conditioned place preference (SCPP) procedure, we demonstrate that social proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive to social contact. Importantly, this strain-dependent difference was not related to phenotypic variability in exploratory behavior or contextual learning nor influenced by the genetic background associated with maternal care or social conditioning. Furthermore, the SCPP phenotype was expressed early in development (postnatal day 25) and did not require a specific sex composition within the conditioning group. Finally, SCPP responses resulted from an interaction between two specifiable processes: one component of the interaction facilitated approach toward environments that were associated with social salience, whereas a second component mediated avoidance of environmental cues that predicted social isolation. We have thus identified a genetically prescribed process that can attribute value onto conditions predicting a general form of social contact. To our knowledge, this is the first definitive evidence to show that genetic variation can influence a form of social valuation not directly related to a reproductive behavior

General psychopathology, internalising and externalising in children and functional outcomes in late adolescence

Background: Internalising and externalising problems commonly co-occur in childhood. Yet, few developmental models describing the structure of child psychopathology appropriately account for this comorbidity. We evaluate a model of childhood psychopathology that separates the unique and shared contribution of individual psychological symptoms into specific internalising, externalising and general psychopathology factors and assess how these general and specific factors predict long-term outcomes concerning criminal behaviour, academic achievement and affective symptoms in three independent cohorts. Methods: Data were drawn from independent birth cohorts (Avon Longitudinal Study of Parents and Children (ALSPAC), N = 11,612; Generation R, N = 7,946; Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN), N = 408). Child psychopathology was assessed between 4 and 8 years using a range of diagnostic and questionnaire-based measures, and multiple informants. First, structural equation models were used to assess the fit of hypothesised models of shared and unique components of psychopathology in all cohorts. Once the model was chosen, linear/logistic regressions were used to investigate whether these factors were associated with important outcomes such as criminal behaviour, academic achievement and well-being from late adolescence/early adulthood. Results: The model that included specific factors for internalising/externalising and a general psychopathology factor capturing variance shared between symptoms regardless of their classification fits well for all of the cohorts. As hypothesised, general psychopathology factor scores were predictive of all outcomes of later functioning, while specific internalising factor scores predicted later internalising outcomes. Specific externalising factor scores, capturing variance not shared by any other psychological symptoms, were not predictive of later outcomes. Conclusions: Early symptoms of psychopathology carry information that is syndrome-specific as well as indicative of general vulnerability and the informant reporting on the child. The ‘general psychopathology factor’ might be more relevant for long-term outcomes than specific symptoms. These findings emphasise the importance of considering the co-occurrence of common internalising and externalising problems in childhood when considering long-term impact

Maternal prenatal anxiety and the fetal origins of epigenetic aging

Stress and Psychopatholog

Maternal antenatal depression and child mental health: moderation by genomic risk for attention-deficit/hyperactivity disorder

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 x 10(-4), R-2 = .18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 x 10(-9), R-2 = .27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health.Stress and Psychopatholog

Aligning the goals of learning analytics with its research scholarship: an open peer commentary approach

To promote cross-community dialogue on matters of significance within the field of learning analytics (LA), we as editors-in-chief of the Journal of Learning Analytics (JLA) have introduced a section for papers that are open to peer commentary. An invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. The 26 authors of the accepted commentaries are based in Europe, North America, and Australia. They range in experience from PhD students and early-career researchers to some of the longest-standing, most senior members of the learning analytics community. This paper brings those commentaries together, and we recommend reading it as a companion piece to the original paper by Motz et al. (2023), which also appears in this issue.Horizon 2020(H2020)883588Algorithms and the Foundations of Software technolog