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Introduction: Individualizing risk for stroke following a transient ischemic attack (TIA) is a topic of intense research, as existing scores are context-dependent or have not been well validated. The Canadian TIA Score stratifies risk of subsequent stroke into low, moderate and high risk. Our objective was to prospectively validate the Canadian TIA Score in a new cohort of emergency department (ED) patients. Methods: We conducted a prospective cohort study in 14 Canadian EDs over 4 years. We enrolled consecutive adult patients with an ED visit for TIA or nondisabling stroke. Treating physicians recorded standardized clinical variables onto data collection forms. Given the ability of prompt emergency carotid endarterectomy (CEA) to prevent stroke (NNT = 3) in high risk patients, our primary outcome was the composite of subsequent stroke or CEA ≤7 days. We conducted telephone follow-up using the validated Questionnaire for Verifying Stroke Free Status at 7 and 90 days. Outcomes were adjudicated by panels of 3 local stroke experts, blinded to the index ED data collection form. Based on prior work, we estimated a sample size of 5,004 patients including 93 subsequent strokes, would yield 95% confidence bands of +/− 10% for sensitivity and likelihood ratio (LR). Our analyses assessed interval LRs (iLR) with 95% CIs. Results: We prospectively enrolled 7,569 patients with mean 68.4 +/−14.7 years and 52.4% female, of whom 107 (1.4%) had a subsequent stroke and 74 (1.0%) CEA ≤7 days (total outcomes = 181). We enrolled 81.2% of eligible patients; missed patients were similar to enrolled. The Canadian TIA Score stratified the stroke/CEA ≤7days risk as: Low (probability <0.2%, iLR 0.20 [95%CI 0.091-0.44]; Moderate (probability 1.3%, iLR 0.79 [0.68-0.92]; High (probability 2.6%, iLR 2.2 [1.9-2.6]. Sensitivity analysis for just stroke ≤7 days yielded similar results: Low iLR 0.17 [95%CI 0.056-0.52], Medium iLR 0.89 [0.75-1.1], High iLR 2.0 [1.6-2.4]. Conclusion: The Canadian TIA Score accurately identifies TIA patients risk for stroke/CEA ≤7 days. Patients classified as low risk can be safely discharged following a careful ED assessment with elective follow-up. Patients at moderate risk can undergo additional testing in the ED, have antithrombotic therapy optimized, and be offered early stroke specialist follow-up. Patients at high risk should in most cases be fully investigated and managed ideally in consultation with a stroke specialist during their index ED visit.
A considerable body of evidence suggests that early caregiving may affect the short-term functioning and longer term development of the hypothalamic–pituitary–adrenocortical axis. Despite this, most research to date has been cross-sectional in nature or restricted to relatively short-term longitudinal follow-ups. More important, there is a paucity of research on the role of caregiving in low- and middle-income countries, where the protective effects of high-quality care in buffering the child's developing stress regulation systems may be crucial. In this paper, we report findings from a longitudinal study (N = 232) conducted in an impoverished periurban settlement in Cape Town, South Africa. We measured caregiving sensitivity and security of attachment in infancy and followed children up at age 13 years, when we conducted assessments of hypothalamus–pituitary–adrenocortical axis reactivity, as indexed by salivary cortisol during the Trier Social Stress Test. The findings indicated that insecure attachment was predictive of reduced cortisol responses to social stress, particularly in boys, and that attachment status moderated the impact of contextual adversity on stress responses: secure children in highly adverse circumstances did not show the blunted cortisol response shown by their insecure counterparts. Some evidence was found that sensitivity of care in infancy was also associated with cortisol reactivity, but in this case, insensitivity was associated with heightened cortisol reactivity, and only for girls. The discussion focuses on the potentially important role of caregiving in the long-term calibration of the stress system and the need to better understand the social and biological mechanisms shaping the stress response across development in low- and middle-income countries.
To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period.
We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up.
Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases.
Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.
We present preliminary results from a number of deep radio polarization surveys being made of the Magellanic Clouds at 2.3 GHz, 4.75 GHz and 8.55 GHz. Extended and linearly polarized radio emission has been found at 2.3 and 4.75 GHz from both the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC). However, as the analysis of these data is not yet complete we present only some of the 4.75 GHz results at this time.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Effect of cannabis use on memory function is a contentious issue, with effects being different in healthy individuals and patients with psychosis.
Employing a meta-analytic approach we investigated the effects of cannabis use on memory function in patients with psychosis and healthy individuals, and the effect of diagnosis, memory dimension and moderating factors. A total of 88 studies were identified through a systematic literature search, investigating healthy (n = 7697) and psychotic (n = 3261) individuals. Standardized mean differences between the cannabis user and non-user groups on memory tasks were estimated using random-effects models and the effect-size statistic Cohen's d. Effects of potential moderating factors were tested using mixed-effects models and subgroup analyses.
We found that cannabis use was associated with significantly (p ⩽ 0.05) impaired global (d = 0.27) and prospective memory (d = 0.61), verbal immediate (d = 0.40) and delayed (d = 0.36) recall as well as visual recognition (d = 0.41) in healthy individuals, but a better global memory (d = −0.11), visual immediate recall (d = −0.73) and recognition (d = −0.42) in patients. Lower depression scores and younger age appeared to attenuate the effects of cannabis on memory. Cannabis-using patients had lower levels of depression and were younger compared with non-using patients, whilst healthy cannabis-users had higher depression scores than age-matched non-users. Longer duration of abstinence from cannabis reduced the effects on memory in healthy and patient users.
These results suggest that cannabis use is associated with a significant domain-specific impairment in memory in healthy individuals but not in cannabis-using patients, suggesting that they may represent a less developmentally impaired subgroup of psychotic patients.
The amplitude of the cortically generated somatosensory evoked potential (SSEP) is used to predict outcome in comatose patients. The relationship between epileptiform discharges and SSEP amplitude has not been elucidated in those patients.
Bilateral median nerve SSEP and electroencephalograph (EEG) studies were performed in a comatose patient (patient 1) 1 day after cardiac surgery and repeated 4 days later. He had tranexamic acid administered before and during surgery. Another comatose patient (patient 2) had the same studies performed 1 day after sustaining 10 minutes of pulseless electrical cardiac activity.
Both comatose patients had epileptiform discharges (on EEG) that were coincident with giant cortically generated SSEPs. In patient 1, the EEG and SSEP studies repeated 5 days postoperatively showed no epileptiform discharges, and the cortically generated SSEP amplitude was decreased (normalized) compared with that obtained one day postoperatively. He emerged from coma and had a good recovery. Patient 2 died shortly after EEG and SSEP testing.
Epileptiform discharges were associated with giant cortically generated median nerve SSEP amplitude (tranexamic acid was implicated in patient 1 and anoxic brain injury in patient 2). Accordingly, those who use the amplitude of cortically generated SSEPs for predicting outcome in comatose patients should consider the presence of epileptiform discharges (detected by EEG) as a potential confounding factor.
Emotional and behavioral problems are commonly associated with substance use in adolescence but it is unclear whether substance use precedes or follows mental health problems. The aim was to investigate longitudinal associations between externalizing and internalizing psychopathology and substance use in a prospective population study design.
The sample was the Northern Finland Birth Cohort 1986 Study (NFBC 1986; n = 6349; 3103 males). Externalizing and internalizing mental health problems were assessed at age 8 years (Rutter scales), substance use and externalizing and internalizing problems [Youth Self-Report (YSR)] at age 15–16 years, and hospital diagnoses for internalizing disorders (age 25) and criminal offences (age 20) from nationwide registers in adulthood.
Externalizing problems at age 8 were associated with later substance use. After adjustment for sociodemographic factors, parental alcohol use and psychiatric disorders, and earlier externalizing and internalizing problems, substance use predicted criminality, especially among males, with the highest odds ratio (OR) for cannabis use [adjusted OR 6.2, 95% confidence interval (CI) 3.1–12.7]. Early internalizing problems were not a risk for later substance use. Female adolescent cannabis (OR 3.2, 95% CI 1.4–7.3) and alcohol (OR 2.1, 95% CI 1.1–4.2) use predicted internalizing disorders in adulthood.
Externalizing problems precede adolescent substance use in both genders, whereas, among boys, substance use also precedes criminal offences. Internalizing problems may follow substance use in females. These associations were robust even when taking into account previous mental health problems.
Clinical depression is associated with reductions in white-matter integrity in several long tracts of the brain. The extent to which these findings are localized or related to depressive symptoms or personality traits linked to disease risk remains unclear.
Members of the Lothian Birth Cohort 1936 (LBC936) were assessed in two waves at mean ages of 70 and 73 years. At wave 1, they underwent assessments of depressive symptoms and the personality traits of neuroticism and extraversion. Brain diffusion magnetic resonance imaging (MRI) data were obtained at the second wave and mood assessments were repeated. We tested whether depressive symptoms were related to reduced white-matter tract fractional anisotropy (FA), a measure of integrity, and then examined whether high neuroticism or low extraversion mediated this relationship.
Six hundred and sixty-eight participants provided useable data. Bilateral uncinate fasciculus FA was significantly negatively associated with depressive symptoms at both waves (standardized β=0.12–0.16). Higher neuroticism and lower extraversion were also significantly associated with lower uncinate FA bilaterally (standardized β=0.09–0.15) and significantly mediated the relationship between FA and depressive symptoms.
Trait liability to depression and depressive symptoms are associated with reduced structural connectivity in tracts connecting the prefrontal cortex with the amygdala and anterior temporal cortex. These effects suggest that frontotemporal disconnection is linked to the etiology of depression, in part through personality trait differences.
The engineering of strained semiconductor materials represents an important aspect of the enhancement in CMOS device performance required for current and future generations of microelectronic technology. An understanding of the mechanical response of the Si channel regions and their environment is key to the prediction and design of device operation. Because of the complexity of the composite geometries associated with microelectronic circuitry, in situ characterization at a submicron resolution is necessary to verify the predicted strain distributions. Of the measurement techniques commonly used for strain characterization, synchrotron-based X-ray microbeam diffraction represents the best nondestructive method to provide spatially resolved information. The mapping of strain distributions in silicon-on-insulator (SOI) features induced by overlying silicon nitride structures and embedded heteroepitaxial features adjacent to SOI device channels are presented. The interaction regions of the SOI strain were observed to extend large distances from the SOI/stressor interfaces leading to significant overlap in the strain distributions at technically relevant dimensions. Experimental data were also compared to several mechanical models to assess their validity in predicting these strain distributions.