Correcting for the Dependence Structure in Social Networks

The use of social network data has recently become increasingly prevalent in social science research and in clinical fields. While some researchers deliberately exploit the social network structures to maximize response rates, reach hidden populations, or learn about the transmission of information or diseases from one person to another through network connections, others unintentionally sample observations from connected networks within the overall target population; the latter is especially common when samples are collected from contiguous geographic areas or similar institutions. Statistical inference from observations sampled from social networks is problematic because the observations are often inherently correlated, but this dependence is rarely adequately accounted for in statistical inference. Failing to account for the dependence between network observations has unfavorable, sometimes dangerous, consequences for inference, causing underestimated standard errors, inflated statistical significance, and high type I error rates. Throughout this work, we demonstrate the gravity of these repercussions through simulations, which entail constructing network structures resembling realistic social networks, associating independent outcomes with each subject, and generating various levels of dependence in the sample. We sample the generated outcome data to draw inferences about the population mean, incorrectly assuming independence between observations. We find that ignoring network dependence has devastating consequences for the validity of inference, and become more severe with increasing correlation: estimated coverage of 95% confidence intervals dropped as low as 33% when the sample exhibited high dependence. We suggest informal methods for quantifying and accounting for dependence in various research settings, but each with the objective of drawing valid inferences for a population mean. We demonstrate the efficacy of these methods by implementing them in all simulated dependence settings. We found that by employing these methods, we were able to attain valid, or nearly valid, inference which we assess through estimated coverage. An important objective of future work in this area is to extend these methods to allow for more general applications

Circumferential strain predicts major adverse cardiovascular events following an acute ST-segment-elevation myocardial infarction

Purpose: To investigate the prognostic value of circumferential left ventricular (LV) strain measured by using cardiac MRI for prediction of major adverse cardiac events (MACE) following an acute ST-segment–elevation myocardial infarction (STEMI). Materials and Methods: Participants with acute STEMI were prospectively enrolled from May 11, 2011, to November 22, 2012. Cardiac MRI was performed at 1.5 T during the index hospitalization. Displacement encoding with stimulated echoes (DENSE) and feature tracking of cine cardiac MRI was used to assess circumferential LV strain. MACE that occurred after discharge were independently assessed by cardiologists blinded to the baseline observations. Results: A total of 259 participants (mean age, 58 years ± 11 [standard deviation]; 198 men [mean age, 58 years ± 11] and 61 women [mean age, 58 years ± 12]) underwent cardiac MRI 2.2 days ± 1.9 after STEMI. Average infarct size was 18% ± 13 of LV mass and circumferential strain was −13% ± 3 (DENSE method) and −24% ± 7 (feature- tracking method). Fifty-one percent (131 of 259 participants) had presence of microvascular obstruction. During a median follow-up period of 4 years, 8% (21 of 259) experienced MACE. Area under the curve (AUC) for DENSE was different from that of feature tracking (AUC, 0.76 vs 0.62; P = .03). AUC for DENSE was similar to that of initial infarct size (P = .06) and extent of microvascular obstruction (P = .08). DENSE-derived strain provided incremental prognostic benefit over infarct size for prediction of MACE (hazard ratio, 1.3; P < .01). Conclusion: Circumferential strain has independent prognostic importance in study participants with acute ST-segment–elevation myocardial infarction

Predictors of segmental myocardial functional recovery in patients after an acute ST-elevation myocardial infarction

Objective: We hypothesized that Displacement Encoding with Stimulated Echoes (DENSE) and feature-tracking derived circumferential strain would provide incremental prognostic value over the extent of infarction for recovery of segmental myocardial function. Methods: Two hundred and sixty-one patients (mean age 59 years, 73% male) underwent MRI 2 days post-ST elevation myocardial infarction (STEMI) and 241 (92%) underwent repeat imaging 6 months later. The MRI protocol included cine, 2D-cine DENSE, T2 mapping and late enhancement. Wall motion scoring was assessed by 2-blinded observers and adjudicated by a third. (WMS: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic). WMS improvement was defined as a decrease in WMS ≥ 1, and normalization where WMS = 1 on follow-up. Segmental circumferential strain was derived utilizing DENSE and feature-tracking. A generalized linear mixed model with random effect of subject was constructed and used to account for repeated sampling when investigating predictors of segmental myocardial improvement or normalization Results: At baseline and follow-up, 1416 segments had evaluable data for all parameters. Circumferential strain by DENSE (p < 0.001) and feature-tracking (p < 0.001), extent of oedema (p < 0.001), infarct size (p < 0.001), and microvascular obstruction (p < 0.001) were associates of both improvement and normalization of WMS. Circumferential strain provided incremental predictive value even after accounting for infarct size, extent of oedema and microvascular obstruction, for segmental improvement (DENSE: odds ratio, 95% confidence intervals: 1.08 per −1% peak strain, 1.05–1.12, p < 0.001, feature-tracking: odds ratio, 95% confidence intervals: 1.05 per −1% peak strain, 1.03–1.07, p < 0.001) and segmental normalization (DENSE: 1.08 per −1% peak strain, 1.04–1.12, p < 0.001, feature-tracking: 1.06 per −1% peak strain, 1.04–1.08, p < 0.001). Conclusions: Circumferential strain provides incremental prognostic value over segmental infarct size in patients post STEMI for predicting segmental improvement or normalization by wall-motion scoring

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria

Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15), 80 microg of AMA1-C1/Alhydrogel (n = 30), or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30).Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.ClinicalTrials.gov NCT00344539

From upright to upside-down presentation: A spatio-temporal ERP study of the parametric effect of rotation on face and house processing

<p>Abstract</p> <p>Background</p> <p>While there is a general agreement that picture-plane inversion is more detrimental to face processing than to other seemingly complex visual objects, the origin of this effect is still largely debatable. Here, we address the question of whether face inversion reflects a quantitative or a qualitative change in processing mode by investigating the pattern of event-related potential (ERP) response changes with picture plane rotation of face and house pictures. Thorough analyses of topographical (Scalp Current Density maps, SCD) and dipole source modeling were also conducted.</p> <p>Results</p> <p>We find that whilst stimulus orientation affected in a similar fashion participants' response latencies to make face and house decisions, only the ERPs in the N170 latency range were modulated by picture plane rotation of faces. The pattern of N170 amplitude and latency enhancement to misrotated faces displayed a curvilinear shape with an almost linear increase for rotations from 0° to 90° and a dip at 112.5° up to 180° rotations. A similar discontinuity function was also described for SCD occipito-temporal and temporal current foci with no topographic distribution changes, suggesting that upright and misrotated faces activated similar brain sources. This was confirmed by dipole source analyses showing the involvement of bilateral sources in the fusiform and middle occipital gyri, the activity of which was differentially affected by face rotation.</p> <p>Conclusion</p> <p>Our N170 findings provide support for both the quantitative and qualitative accounts for face rotation effects. Although the qualitative explanation predicted the curvilinear shape of N170 modulations by face misrotations, topographical and source modeling findings suggest that the same brain regions, and thus the same mechanisms, are probably at work when processing upright and rotated faces. Taken collectively, our results indicate that the same processing mechanisms may be involved across the whole range of face orientations, but would operate in a non-linear fashion. Finally, the response tuning of the N170 to rotated faces extends previous reports and further demonstrates that face inversion affects perceptual analyses of faces, which is reflected within the time range of the N170 component.</p

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development