The time course of implicit affective picture processing: an eye movement study

Consistent with a negativity bias account, neuroscientific and behavioral evidence demonstrates modulation of even early sensory processes by unpleasant, potentially threat-relevant information. The aim of this research is to assess the extent to which pleasant and unpleasant visual stimuli presented extrafoveally capture attention and impact eye movement control. We report an experiment examining deviations in saccade metrics in the presence of emotional image distractors that are close to a nonemotional target. We additionally manipulate the saccade latency to test when the emotional distractor has its biggest impact on oculomotor control. The results demonstrate that saccade landing position was pulled toward unpleasant distractors, and that this pull was due to the quick saccade responses. Overall, these findings support a negativity bias account of early attentional control and call for the need to consider the time course of motivated attention when affect is implicit

Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction

BACKGROUND: Fibroblast growth factor 9 (FGF9) is secreted from bone marrow cells, which have been shown to improve systolic function after myocardial infarction (MI) in a clinical trial. FGF9 promotes cardiac vascularization during embryonic development but is only weakly expressed in the adult heart. METHODS AND RESULTS: We used a tetracycline-responsive binary transgene system based on the α-myosin heavy chain promoter to test whether conditional expression of FGF9 in the adult myocardium supports adaptation after MI. In sham-operated mice, transgenic FGF9 stimulated left ventricular hypertrophy with microvessel expansion and preserved systolic and diastolic function. After coronary artery ligation, transgenic FGF9 enhanced hypertrophy of the noninfarcted left ventricular myocardium with increased microvessel density, reduced interstitial fibrosis, attenuated fetal gene expression, and improved systolic function. Heart failure mortality after MI was markedly reduced by transgenic FGF9, whereas rupture rates were not affected. Adenoviral FGF9 gene transfer after MI similarly promoted left ventricular hypertrophy with improved systolic function and reduced heart failure mortality. Mechanistically, FGF9 stimulated proliferation and network formation of endothelial cells but induced no direct hypertrophic effects in neonatal or adult rat cardiomyocytes in vitro. FGF9-stimulated endothelial cell supernatants, however, induced cardiomyocyte hypertrophy via paracrine release of bone morphogenetic protein 6. In accord with this observation, expression of bone morphogenetic protein 6 and phosphorylation of its downstream targets SMAD1/5 were increased in the myocardium of FGF9 transgenic mice. CONCLUSIONS: Conditional expression of FGF9 promotes myocardial vascularization and hypertrophy with enhanced systolic function and reduced heart failure mortality after MI. These observations suggest a previously unrecognized therapeutic potential for FGF9 after MI.

FACSGen 2.0 animation software: generating three-dimensional FACS-valid facial expressions for emotion research

In this article, we present FACSGen 2.0, new animation software for creating static and dynamic threedimensional facial expressions on the basis of the Facial Action Coding System (FACS). FACSGen permits total control over the action units (AUs), which can be animated at all levels of intensity and applied alone or in combination to an infinite number of faces. In two studies, we tested the validity of the software for the AU appearance defined in the FACS manual and the conveyed emotionality of FACSGen expressions. In Experiment 1, four FACS-certified coders evaluated the complete set of 35 single AUs and 54 AU combinations for AU presence or absence, appearance quality, intensity, and asymmetry. In Experiment 2, lay participants performed a recognition task on emotional expressions created with FACSGen software and rated the similarity of expressions displayed by human and FACSGen faces. Results showed good to excellent classification levels for all AUs by the four FACS coders, suggesting that the AUs are valid exemplars of FACS specifications. Lay participants’ recognition rates for nine emotions were high, and comparisons of human and FACSGen expressions were very similar. The findings demonstrate the effectiveness of the software in producing reliable and emotionally valid expressions, and suggest its application in numerous scientific areas, including perception, emotion, and clinical and euroscience research.

Partially identified treatment effects under imperfect compliance: the case of domestic violence

The Minneapolis Domestic Violence Experiment (MDVE) is a randomized social experiment with imperfect compliance which has been extremely influential in how police officers respond to misdemeanor domestic violence. This paper re-examines data from the MDVE, using recent literature on partial identification to find recidivism associated with a policy that arrests misdemeanor domestic violence suspects rather than not arresting them. Using partially identified bounds on the average treatment effect I find that arresting rather than not arresting suspects can potentially reduce recidivism by more than two-and-a-half times the corresponding intent-to-treat estimate and more than two times the corresponding local average treatment effect, even when making minimal assumptions on counterfactuals.

Increases in prefrontal cortex activity when regulating negative emotion predicts symptom severity trajectory over six months in depression

Context: Emotion regulation is critically disrupted in depression and use of paradigms tapping these processes may uncover essential changes in neurobiology during treatment. In addition, as neuroimaging outcome studies of depression commonly utilize solely baseline and endpoint data – which is more prone to week-to week noise in symptomatology – we sought to use all data points over the course of a six month trial. Objective: To examine changes in neurobiology resulting from successful treatment. Design: Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from one of two antidepressant treatments over a six month trial. Participants were scanned pretreatment, at 2 months and 6 months posttreatment. Setting: University functional magnetic resonance imaging facility. Participants: 21 patients with Major Depressive Disorder and without other Axis I or Axis II diagnoses and 14 healthy controls. Interventions: Venlafaxine XR (doses up to 300mg) or Fluoxetine (doses up to 80mg). Main Outcome Measure: Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm as well as regular assessments of symptom severity by the Hamilton Rating Scale for Depression. To utilize all data points, slope trajectories were calculated for rate of change in depression severity as well as rate of change of neural engagement. Results: Those depressed individuals showing the steepest decrease in depression severity over the six months were those individuals showing the most rapid increases in BA10 and right DLPFC activity when regulating negative affect over the same time frame. This relationship was more robust than when using solely the baseline and endpoint data. Conclusions: Changes in PFC engagement when regulating negative affect correlate with changes in depression severity over six months. These results are buttressed by calculating these statistics which are more reliable and robust to week-to-week variation than difference scores.

Therapeutic benefit of low-dose clopidogrel in patients undergoing carotid surgery is linked to variability in the platelet adenosine diphosphate response and patients' weight

BACKGROUND AND PURPOSE: We have previously shown that a single 75-mg tablet of clopidogrel, taken before carotid endarterectomy, significantly reduces postoperative embolization, a marker of thromboembolic stroke. This study explores the antiplatelet effect of this submaximal dose. METHODS: Fifty-six patients on long-term aspirin (150 mg) were randomized to 75 mg clopidogrel or placebo before carotid endarterectomy. Blood samples were taken pre- and postdrug administration and at the end of surgery to measure platelet activation and adenosine diphosphate (ADP) response by flow cytometry and aggregometry. RESULTS: Surgery produced a significant rise in platelet activation in vivo as evidenced by a rise in the percentage of monocyte-platelet aggregates in patients given placebo, but this was not seen in patients receiving clopidogrel. Before surgery, clopidogrel produced a significant reduction in the platelet response to ADP; for example, with 10(-6)M ADP, 77.32+/-2.3% bound fibrinogen in placebo group compared with 67.16+/-3.1% after clopidogrel (P=0.01). This was accentuated after surgery when the percentage of platelets binding fibrinogen in response to ADP was 76.53+/-2.2% in patients given placebo and 62.84+/-3.3% in the clopidogrel group (P=0.002). Similar differences were seen over a range of ADP concentrations and by aggregometry. Platelet responsiveness before treatment was highly variable and was positively correlated with the inhibitory effect of clopidogrel; patients with the highest baseline response to ADP showed the greatest response to clopidogrel. A negative correlation was seen between the effect of clopidogrel and patients' weight (r=0.57; P=0.002). CONCLUSIONS: These results explain how a single 75-mg dose of clopidogrel produces a significant clinical impact on embolization.

Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation

CONTEXT: The link between long-haul air travel and venous thromboembolism is the subject of continuing debate. It remains unclear whether the reduced cabin pressure and oxygen tension in the airplane cabin create an increased risk compared with seated immobility at ground level. OBJECTIVE: To determine whether hypobaric hypoxia, which may be encountered during air travel, activates hemostasis. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, crossover study, performed in a hypobaric chamber, to assess the effect of an 8-hour seated exposure to hypobaric hypoxia on hemostasis in 73 healthy volunteers, which was conducted in the United Kingdom from September 2003 to November 2005. Participants were screened for factor V Leiden G1691A and prothrombin G20210A mutation and were excluded if they tested positive. Blood was drawn before and after exposure to assess activation of hemostasis. INTERVENTIONS: Individuals were exposed alternately (> or =1 week apart) to hypobaric hypoxia, similar to the conditions of reduced cabin pressure during commercial air travel (equivalent to atmospheric pressure at an altitude of 2438 m), and normobaric normoxia (control condition; equivalent to atmospheric conditions at ground level, circa 70 m above sea level). MAIN OUTCOME MEASURES: Comparative changes in markers of coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation. RESULTS: Changes were observed in some hemostatic markers during the normobaric exposure, attributed to prolonged sitting and circadian variation. However, there were no significant differences between the changes in the hypobaric and the normobaric exposures. For example, the median difference in change between the hypobaric and normobaric exposure was 0 ng/mL for thrombin-antithrombin complex (95% CI, -0.30 to 0.30 ng/mL); -0.02 [corrected] nmol/L for prothrombin fragment 1 + 2 (95% CI, -0.03 to 0.01 nmol/L); 1.38 ng/mL for D-dimer (95% CI, -3.63 to 9.72 ng/mL); and -2.00% for endogenous thrombin potential (95% CI, -4.00% to 1.00%). CONCLUSION: Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.

Rap1-Rac1 circuits potentiate platelet activation.

OBJECTIVE: The goal of this study was to investigate the potential crosstalk between Rap1 and Rac1, 2 small GTPases central to platelet activation, particularly downstream of the collagen receptor GPVI. METHODS AND RESULTS: We compared the activation response of platelets with impaired Rap signaling (double knock-out; deficient in both the guanine nucleotide exchange factor, CalDAG-GEFI, and the Gi-coupled receptor for ADP, P2Y12), to that of wild-type platelets treated with a small-molecule Rac inhibitor, EHT 1864 (wild-type /EHT). We found that Rac1 is sequentially activated downstream of Rap1 on stimulation via GPVI. In return, Rac1 provides important feedback for both CalDAG-GEFI- and P2Y12-dependent activation of Rap1. When analyzing platelet responses controlled by Rac1, we observed (1) impaired lamellipodia formation, clot retraction, and granule release in both double knock-out and EHT 1864-treated wild-type platelets; and (2) reduced calcium store release in EHT 1864-treated wild-type but not double knock-out platelets. Consistent with the latter finding, we identified 2 pools of Rac1, one activated immediately downstream of GPVI and 1 activated downstream of Rap1. CONCLUSIONS: We demonstrate important crosstalk between Rap1 and Rac1 downstream of GPVI. Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12-dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively.

The contributions of domain-general and numerical factors to third-grade arithmetic skills and mathematical learning disability

Explanations of the marked individual differences in elementary school mathematical achievement and mathematical learning disability (MLD or dyscalculia) have involved domain-general factors (working memory, reasoning, processing speed and oral language) and numerical factors that include single-digit processing efficiency and multi-digit skills such as number system knowledge and estimation. This study of third graders (N = 258) finds both domain-general and numerical factors contribute independently to explaining variation in three significant arithmetic skills: basic calculation fluency, written multi-digit computation, and arithmetic word problems. Estimation accuracy and number system knowledge show the strongest associations with every skill and their contributions are both independent of each other and other factors. Different domain-general factors independently account for variation in each skill. Numeral comparison, a single digit processing skill, uniquely accounts for variation in basic calculation. Subsamples of children with MLD (at or below 10th percentile, n = 29) are compared with low achievement (LA, 11th to 25th percentiles, n = 42) and typical achievement (above 25th percentile, n = 187). Examination of these and subsets with persistent difficulties supports a multiple deficits view of number difficulties: most children with number difficulties exhibit deficits in both domain-general and numerical factors. The only factor deficit common to all persistent MLD children is in multi-digit skills. These findings indicate that many factors matter but multi-digit skills matter most in third grade mathematical achievement.

Effect of forage conservation method on plasma lipids, mammary lipogenesis, and milk fatty acid composition in lactating cows fed diets containing a 60:40 forage-to-concentrate ratio

The effects of forage conservation method on plasma lipids, mammary lipogenesis, and milk fat were examined in 2 complementary experiments. Treatments comprised fresh grass, hay, or untreated (UTS) or formic acid treated silage (FAS) prepared from the same grass sward. Preparation of conserved forages coincided with the collection of samples from cows fed fresh grass. In the first experiment, 5 multiparous Finnish Ayrshire cows (229 d in milk) were used to compare a diet based on fresh grass followed by hay during 2 consecutive 14-d periods, separated by a 5-d transition during which extensively wilted grass was fed. In the second experiment, 5 multiparous Finnish Ayrshire cows (53 d in milk) were assigned to 1 of 2 blocks and allocated treatments according to a replicated 3 × 3 Latin square design, with 14-d periods to compare hay, UTS, and FAS. Cows received 7 or 9 kg/d of the same concentrate in experiments 1 and 2, respectively. Arterial concentrations of triacylglycerol (TAG) and phospholipid were higher in cows fed fresh grass, UTS, and FAS compared with hay. Nonesterified fatty acid (NEFA) concentrations and the relative abundance of 18:2n-6 and 18:3n-3 in TAG of arterial blood were also higher in cows fed fresh grass than conserved forages. On all diets, TAG was the principle source of fatty acids (FA) for milk fat synthesis, whereas mammary extraction of NEFA was negligible, except during zero-grazing, which was associated with a lower, albeit positive calculated energy balance. Mammary FA uptake was higher and the synthesis of 16:0 lower in cows fed fresh grass than hay. Conservation of grass by drying or ensiling had no influence on mammary extraction of TAG and NEFA, despite an increase in milk fat secretion for silages compared with hay and for FAS than UTS. Relative to hay, milk fat from fresh grass contained lower 12:0, 14:0, and 16:0 and higher S3,R7,R11,15-tetramethyl-16:0, cis-9 18:1, trans-11 18:1, cis-9,trans-11 18:2, 18:2n-6, and 18:3n-3 concentrations. Even though conserved forages altered mammary lipogenesis, differences in milk FA composition were relatively minor, other than a higher enrichment of S3,R7,R11,15-tetramethyl-16:0 in milk from silages compared with hay. In conclusion, differences in milk fat composition on fresh grass relative to conserved forages were associated with a lower energy balance, increased uptake of preformed FA, and decreased synthesis of 16:0 de novo in the mammary glands, in the absence of alterations in stearoyl-coenzyme A desaturase activity.

Interpretation bias in preschool children at risk for anxiety: a prospective study

A story-stem paradigm was used to assess interpretation bias in preschool children. Data were available for 131 children. Interpretation bias, behavioural inhibition (BI) and anxiety were assessed when children were aged between 3 years 2 months and 4 years 5 months. Anxiety was subsequently assessed 12-months, 2-years and 5-years later. A significant difference in interpretation bias was found between participants who met criteria for an anxiety diagnosis at baseline, with clinically anxious participants more likely to complete the ambiguous story-stems in a threat-related way. Threat interpretations significantly predicted anxiety symptoms at 12-month follow-up, after controlling for baseline symptoms, but did not predict anxiety symptoms or diagnoses at either 2-year or 5- year follow-up. There was little evidence for a relationship between BI and interpretation bias. Overall, the pattern of results was not consistent with the hypothesis that interpretation bias plays a role in the development of anxiety. Instead, some evidence for a role in the maintenance of anxiety over relatively short periods of time was found. The use of a story-stem methodology to assess interpretation bias in young children is discussed along with the theoretical and clinical implications of the findings.

Competing for attentional priority: temporary goals versus threats

Numerous studies have shown that attention is biased toward threatening events. More recent evidence has also found attentional biases for stimuli that are relevant to the current and temporary goals of an individual. We examined whether goal-relevant information still evokes an attentional bias when this information competes with threatening events. In three experiments, participants performed a dot probe task combined with a separate task that induced a temporary goal. The results of Experiment 1 showed that attention was oriented to goal-relevant pictures in the dot probe task when these pictures were simultaneously presented with neutral or threatening pictures. Whether goal-relevant pictures themselves were threatening or neutral did not influence the results. Experiment 2 replicated these findings in a sample of highly trait-anxious participants. Experiment 3 showed that attention was automatically deployed to stimuli relevant to a temporary goal even in the presence of stimuli that signal imminent and genuine threat (i.e., a colored patch signaling the presentation of an aversive noise). These findings further corroborate the conclusion that an individual's current and temporary goals guide early attentional processes

Allocation of spatial attention to emotional stimuli depends upon arousal and not valence

Attentional allocation to emotional stimuli is often proposed to be driven by valence and in particular by negativity. However, many negative stimuli are also arousing leaving the question whether valence or arousal accounts for this effect. The authors examined whether the valence or the arousal level of emotional stimuli influences the allocation of spatial attention using a modified spatial cueing task. Participants responded to targets that were preceded by cues consisting of emotional pictures varying on arousal and valence. Response latencies showed that disengagement of spatial attention was slower for stimuli high in arousal than for stimuli low in arousal. The effect was independent of the valence of the pictures and not gender-specific. The findings support the idea that arousal affects the allocation of attention.