text:
Figure 1. Psychophysiological responses and blood oxygenation level–dependent reactivity during fear acquisition. A, Mean skin conductance responses (SCRs) during conditioning to the conditioned stimulus paired with the shock (CS+) and to that not paired (CS−). Both the obsessive-compulsive disorder (OCD) and healthy control (HC) groups significantly discriminated between the CS+ and CS− (asterisk denotes P < .05) during the fear conditioning phase. B, Blood oxygenation level–dependent responses to CS+ presentations contrasted with responses to CS− presentations across all conditioning trials within and between groups. Group differences, denoted by the red circle (bottom row), were found in the right caudate nucleus, subgenual cortex, and the hippocampus. Activation maps are illustrated with a threshold of t > ±3.0 (P < .01, uncorrected) within group and a threshold of t > ±1.0 (P < .01, uncorrected) between groups. Results are overlaid on a template structural magnetic resonance image. The scale bar is ±3-5 for within-group contrasts and ±1-4 for between-group contrasts.
Figure 2. Psychophysiological responses and blood oxygenation level–dependent reactivity during extinction training. A, Skin conductance response (SCR) in both the obsessive-compulsive disorder (OCD) and healthy control (HC) groups did not differ at the beginning (first 4 trials, extinguished reinforced conditioned stimulus [eCS+E]) or end of extinction training (last 4 trials; lCS+E) to the CS+E. B, Blood oxygenation level–dependent responses during extinction training are displayed within and between groups. Results display responses to last 4 CS+E presentations contrasted with responses to first 4 CS+E presentations. In this contrast, both the OCD and HC groups displayed deactivation of the dorsal anterior cingulate (top 2 rows), indicating the dorsal anterior cingulate was less activated at the end of extinction training compared with at the beginning. The OCD group showed significantly less activation than the HC group in the right ventromedial prefrontal cortex, denoted by the red circle. Activation maps are illustrated with a threshold of t > ±3.0 (P < .01) within group and a threshold of t > ±1.0 (P < .01) between groups, then overlaid on a template structural magnetic resonance image. The scale bar is ±3-5 for within-group contrasts and ±1-4 for between-group contrasts.
Figure 3. Psychophysiological responses and blood oxygenation level–dependent activations during extinction recall. A, Mean skin conductance responses (SCRs) during recall to the extinguished reinforced conditioned stimulus (CS+E), the nonextinguished CS+ (CS+NE), and the nonreinforced CS (CS−). B, The ability to recall extinction was also assessed by an extinction retention index measure (see the Methods section). There was a significant group difference (* P < .05) in the extinction retention index percentage, indicating that the healthy control (HC) group was better able to recall extinction training compared with the obsessive-compulsive disorder (OCD) group. C, Blood oxygenation level–dependent responses during extinction recall are displayed within and between groups. The OCD group showed significantly less activation than the HC group in the left ventromedial prefrontal cortex, cerebellum, posterior cingulate cortex, and putamen (bottom row, red circles). Results represent responses to the first 4 CS+NE presentations contrasted with responses to the first 4 CS+E presentations during recall. Activation maps are illustrated with a threshold of t > ±3.0 (P < .01, uncorrected) within group and a threshold of t > ±1.0 (P < .01, uncorrected) between groups, then overlaid on a template structural magnetic resonance image. The scale bar is ±3-5 for within-group contrasts and ±1-4 for between-group contrasts.
Figure 4. Correlations of the Yale-Brown Obsessive-Compulsive Scale (YBOCS) with brain reactivity during recall. A, A voxelwise regression analysis of total YBOCS scores during extinction recall indicated a significant correlation of brain activity with symptom severity in 5 brain regions (red circles). The top row displays regions found to have a positive correlation with YBOCS scores, while the bottom row displays regions found to have a negative correlation with YBOCS scores. Activation maps are illustrated with a threshold of t > ±2.0 (P < .01, uncorrected), then overlaid on a template structural magnetic resonance image. B, Model of brain activation prediction of YBOCS scores. Results based on stepwise regression analysis found that insular cortex and cerebellum activation are the most predictive contributors of the 5 brain regions correlated with YBOCS scores. X indicates the region had no role in regression or no contribution to significance in the linear regression model. dACC indicates dorsal anterior cingulate cortex; OCD, obsessive-compulsive disorder; PCC, posterior cingulate cortex; vmPFC, ventromedial prefrontal cortex. * P < .05; † P < .001.
Figure 5. Correlations of the extinction retention index (ERI) score with brain reactivity during recall. A, A voxelwise regression analysis of ERI scores during extinction recall indicated a significant correlation of brain activity with psychophysiological measurements of the ability to recall extinction memory in 5 brain regions (red circles). The top row displays regions found to have a positive correlation with ERI scores, while the bottom row displays regions found to have a negative correlation with ERI scores. Activation maps are illustrated with a threshold of t > ±2.0 (P < .01, uncorrected), then overlaid on a template structural magnetic resonance image. B, Model of brain activation prediction of ERI scores based on a stepwise regression analysis. Results found that dorsal anterior cingulate cortex (dACC) and cerebellum activation are the most predictive contributors of the 5 brain regions correlated with ERI scores. X indicates region did not have any significant contributions to the statistical model tested in the multilinear regression model. PCC indicates posterior cingulate cortex; vmPFC, ventromedial prefrontal cortex. * P < .05; † P < .001.
Figure 6. Ability to recall extinction training correlates with symptom severity. Symptom severity, as measured by the Yale-Brown Obsessive-Compulsive Scale (YBOCS) score, was found to positively correlate with the individual's extinction retention index, a measure indicative of the ability to recall extinction training. The worse the individual's obsessive-compulsive disorder symptoms, the better that ability to recall extinction memory.
Milad MR, Furtak SC, Greenberg JL, et al. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit.. JAMA Psychiatry.. Published online April 17, 2013. doi:10.1001/jamapsychiatry.2013.914.
eAppendix. Methods
eTable 1. Whole-brain results within and between groups for conditioning, extinction, and recall
eTable 2. Correlations between the extracted beta values from YBOCS and ERI-related activations during extinction recall in 5 brain regions: vmPFC, cerebellum, PCC, dACC, and insula cortex
eFigure 1. Illustration of cues presented during the experiment across the different experimental phases and days
eFigure 2. Positive and negative correlations during recall
Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, Jenike M, Rauch SL, Wilhelm S. Deficits in Conditioned Fear Extinction in Obsessive-Compulsive Disorder and Neurobiological Changes in the Fear Circuit. JAMA Psychiatry. 2013;70(6):608–618. doi:10.1001/jamapsychiatry.2013.914
© 2017
Author Affiliations: Department of Psychiatry, Harvard Medical School, and Massachusetts General Hospital, Charlestown (Drs Milad and Furtak and Ms Im); Obsessive-Compulsive and Related Disorders Program, Massachusetts General Hospital, Boston (Drs Greenberg, Jenike, and Wilhelm, and Mss Falkenstein and Keshaviah); and McLean Hospital, Belmont (Dr Rauch), Massachusetts. Dr Furtak is now with the Department of Psychology, California State University, Sacramento, California.
Importance Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The neurobiology of fear regulation and consolidation of safety memories have not been examined in this patient population.
Objective To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD.
Design Cross-sectional, case-control, functional magnetic resonance imaging study.
Setting Academic medical center.
Participants Twenty-one patients with OCD and 21 healthy participants.
Main Outcomes and Measures Skin conductance responses and blood oxygenation level–dependent responses.
Results The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity.
Conclusions and Relevance As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.
Individuals diagnosed as having obsessive-compulsive disorder (OCD) are unable to control or regulate intrusive thoughts, doubts, or concerns about matters in their daily lives, such as safety, cleanliness, violence, or symmetry. These obsessions tend to generate, or be accompanied by, anxiety and fear. Consequently, patients with OCD engage in compulsive repetitive, stereotyped, or ritualized behaviors aimed to neutralize the anxiety and fear associated with their obsessions. Therefore, OCD can be viewed as a disorder of self-regulation and behavioral inhibition.1
Quiz Ref IDPavlovian fear conditioning and extinction is an experimental paradigm commonly used to study the regulation and inhibition of fear memories.2,3 Results from animal and human studies using this paradigm converge to implicate a brain network, including the ventromedial prefrontal cortex (vmPFC), amygdala, and dorsal anterior cingulate cortex (dACC), in the acquisition and expression of the fear extinction memory.2,4 For example, increased activation within the amygdala, insula, and dACC has been observed during fear conditioning and has been associated with the expression of conditioned responses.5- 9 During extinction training, the vmPFC and the amygdala have been shown to exhibit increased reactivity to conditioned stimuli.10,11 When the extinction memory is then recalled, the hippocampus along with the vmPFC have been found to be involved in signaling the recall of extinction memory.10,12 Pavlovian conditioning paradigms have been used to explore the psychopathology of several anxiety disorders, such as posttraumatic stress disorder (PTSD) and panic disorder, as well as schizophrenia.13- 19
While fear conditioning as a model may not best explain the clinical phenomenology of OCD, understanding the neural circuits of fear extinction in OCD could be clinically relevant for several reasons. First, such studies may clarify how anxiety and distress associated with OCD are sustained and may elucidate the mechanisms by which exposure therapies confer their therapeutic effects in this disorder.1 Second, cognitive behavioral therapies used to treat OCD are extinction-based therapies,20 therefore, understanding the neural correlates of extinction may further our understanding of how these therapies help treat patients with OCD and how they can perhaps be augmented. Third, there seems to be overlap between brain regions involved in the psychopathology of OCD and those involved in the acquisition and extinction of conditioned fear. Data using neuroimaging techniques have begun to link the psychopathology of OCD with dysfunctional activation in a network of brain regions, many of which overlap with those involved in fear extinction.1,21 Increased amygdala responses in OCD have been noted in response to emotional faces22 and symptom-provoking stimuli.23 Lesions of the dACC alleviate OCD symptoms24 and pharmacologic treatments have been shown to normalize the activity of this region.25 Hypoactive vmPFC has been observed in patients with OCD, and studies have reported inverse correlations between OCD symptom severity and vmPFC/medial orbitofrontal cortex function (reviewed in an article by Milad and Rauch1). Collectively, these data suggest that fear extinction and its underlying brain network may be altered in patients with OCD and that examining fear extinction in OCD may be useful in understanding how exposure therapies treat patients with OCD.
In this study, we hypothesized that patients with OCD exhibit aberrant fear extinction recall and that these deficits are associated with a dysfunctional fear extinction network. Patients with OCD and healthy control (HC) subjects underwent a validated 2-day fear conditioning and extinction paradigm.26- 28 On day 1, participants were fear conditioned and subsequently extinguished their fear to visual cues. On day 2, subjects underwent the fear extinction recall test to examine the recall of the safety memory formed during extinction learning. The study was conducted in a functional magnetic resonance imaging (fMRI) scanner, and skin conductance responses (SCRs) were collected throughout the study and used as an index of conditioned responding.
Twenty-one right-handed healthy volunteers (10 males) between 20 and 41 years of age (mean [SD], 26.4 [5.2] years) were recruited from the local community. Twenty-one right-handed subjects (7 male) between 20 and 58 years of age (mean [SD], 33.8 [11.3] years) who met the DSM-IV diagnosis criteria for OCD were recruited from the Obsessive-Compulsive and Related Disorders Program at Massachusetts General Hospital. Patients were eligible for participation in the study if they were medication free or taking a stable medication regimen for 8 weeks or more prior to study participation (benzodiazepine free for ≥2 weeks). After a complete study description, including all procedures, written informed consent was obtained in accordance with the Partners Healthcare System Human Research Committee requirements.
The screening visit included a diagnostic interview for Axis I disorders (Structured Clinical Interview for DSM-IV [Patient Edition]). The Yale-Brown Obsessive-Compulsive Scale (YBOCS), a 10-item semistructured clinician-administered measure with demonstrated validity and reliability, was used to assess OCD symptom severity.29,30
The experimental protocol used in this study has been described previously.15,26,31 Briefly, fear conditioning and extinction took place on day 1 and the extinction recall test occurred on day 2. The conditioned stimuli (CS) were pictures of different colored lamps and the unconditioned stimulus was an aversive electrical stimulation to the subject's fingers that coterminated with the CS during conditioning but was never presented during any of the subsequent experimental phases (see eAppendix and eFigure 1A for additional details). Two CS+s were followed by the electric shock during conditioning, but only 1 was presented during the extinction training phase (CS+ extinguished [CS+E]). On day 2, subjects underwent extinction recall, during which the CS+E, as well as the CS+ that was conditioned but not extinguished (CS+NE), were presented. Skin conductance was measured simultaneously with fMRI acquisition, as previously described (eAppendix). Details about the way SCR was calculated and how the extinction retention index (ERI) scores were measured are described the eAppendix. The ERI scores were entered into a linear regression model with the fMRI data during extinction recall (contrast: early CS+E vs early CS+NE) to compute correlations at each voxel. The ERI score of 1 patient with OCD was conservatively changed from −108 to 0 to avoid overestimation of the OCD group deficit.
Our acquisition and analysis parameters were comparable with those previously published5,28,32 and are further detailed in the eAppendix. Statistical Parametric Mapping (SPM8; The Wellcome Trust; www.fil.ion.ucl.ac.uk) was used within a MATLAB (MathWorks) environment on a Linux 64-bit system. Functional images were corrected for slice timing, realigned, coregistered with the structural image, segmented, normalized into the Montreal Neurological Institute template space, and smoothed (8 mm full-width at half maximum). Preprocessed functional time series data were modeled using a general linear model with regressors signifying the stimulus onsets using stick functions.
First-level contrast images were obtained for each subject and then modeled at the second level to examine significant (de)activations both within and between HC and patient groups. To analyze neurocorrelates of fear acquisition, all CS+ trials were contrasted to all CS− trials. Extinction training processes were assessed by contrasting early CS+E trials (first 8 during extinction) to late CS+E (last 8 extinction trials), as previously defined. To examine neurocorrelates of extinction recall, early CS+E trials (first 4) were contrasted to early CS+NE (first 4) trials. As a control, a secondary analysis added age as a nuisance covariate to second-level models of conditioning, extinction, and recall. Overall results were retained except where noted. Two additional analyses used multiple regression to examine whether brain (de)activation during extinction recall correlated with ERI or YBOCS29,30 scores during the contrast of CS+E vs CS+NE.
Given our prior studies in fear extinction of healthy and patient populations, we had strong unidirectional a priori hypotheses regarding the functional (de)activations of several regions. These regions included the insular cortex (during conditioning), dACC (all phases), vmPFC (during extinction training and recall), amygdala (all phases), and hippocampus (all phases).10,28 Additional a priori structures included neurocircuitry implicated in OCD, namely, the striatum (including the caudate nucleus and putamen), posterior cingulate cortex (PCC), orbital frontal cortex (OFC), and cerebellum.33 Within these a priori regions, clusters surviving small-volume correction (5-mm radius sphere) at P < .05 familywise error were considered significant. Outside of these regions, clusters that exceeded 10 voxels and were significant at familywise error–corrected P < .05 were considered significant. The descriptions of other analyses related to demographic and psychophysiological measures are detailed in the eAppendix. Two additional multiple regressions were conducted using stepwise regression methods (see eAppendix for details).
The demographics for both groups, as well as all clinical data related to the OCD group, including comorbidities and medications, and OCD subtypes are described in Table 1. Owing to the significant between-group age difference, additional analyses were conducted to examine the effect of age on neural correlates of the conditioning and extinction paradigm listed here. The results were largely unchanged.
Both the OCD and HC groups displayed stimulus-specific conditioning indicative of learning. Skin conductance responses were significantly different between the CS+ and CS− trials during fear acquisition in both groups (F1,35 = 28.83, P < .001; Figure 1A). There were no significant group differences (F1,35 = 0.99, P > .05) or interactions between the stimulus type and group (F1,35 = 0.15, P > .05), indicating equal levels of fear conditioning between the OCD and HC groups. Regarding the neuroimaging data, Figure 1B shows whole-brain activation for the contrast CS+ vs CS− presentations. Both HC and OCD groups displayed significant activation in the dACC, periaqueductal gray region of the brainstem, and insula (Figure 1B and Table 2).
Between-group analysis revealed that the OCD group failed to engage several regions compared with the HC group (Figure 1B, bottom row). These regions consisted of the right caudate, a region of subgenual cortex, and the hippocampus (Table 2). Brain regions that showed significant (de)activations outside of our a priori regions of interest (ROI) are listed in eTable 1.
To assess learning during extinction training, the first 4 trials (eCS+E) were compared with the last 4 trials (lCS+E). A 2-way analysis of variance compared the level of SCRs (late vs early extinction training) between groups (OCD and HC). There was no significant main effect of SCR (late vs early extinction training, F1,35 = 0.77, P = .39) or group (F1,35 = 2.79, P = .10). There also was no significant interaction between variables (F1,35 = 1.89, P = .18). The results indicated that the OCD group extinguished to a level comparable with the HC group (Figure 2A). Regarding the fMRI data, we observed significant dACC deactivation in both the HC and OCD groups late in extinction to the CS+E as compared with early trials (lCS+E vs eCS+E; Figure 2B and Table 2). These findings are consistent with previous studies suggesting that dACC activation is correlated with fear expression, where both fear expression and dACC activity decrease as extinction training occurs.9 Also consistent with previous studies,10,11,34 the HC group displayed an activation of vmPFC late in extinction training as compared with early extinction (Figure 2B and Table 2), consistent with a role of vmPFC in the development of the extinction memory. Despite apparent extinction as indexed by the SCR data in the OCD group, vmPFC activation was not evident in the OCD group, resulting in a significant group difference (Figure 2B, bottom row; and Table 2). Brain regions that showed significant (de)activations outside of our a priori ROI are listed in eTable 1.
A 2-way analysis of variance conducted on SCRs to the extinguished and nonextinguished stimuli revealed no significant group by stimulus interactions (F3,105 = 0.81, P = .45). There was no significant main effect of stimulus (F2,105 = 2.11, P = .13). However, there was a significant main effect of group (F1,105 = 7.66, P < .01; Figure 3A). The mean SCR collapsed across all stimuli was significantly higher in the OCD group than the HC group. A 1-way analysis of variance was conducted to test whether responses to the stimuli differed within the OCD group. The results displayed a trend to this effect (P = .07). The results obtained from the ERI analysis were clearer. Here, an independent t test resulted in a significant group difference (t34 = −2.63, P < .05; Figure 3B).
Regarding the fMRI results for this phase, the HC group displayed significant activation of the vmPFC to the CS+E as compared with the CS+NE (Table 2), consistent with our findings and other previous findings.10,28 This was not observed in the OCD group, resulting in a significant difference between the groups (Table 2). We also observed a region of PCC that was significantly activated in the HC group that was not evident in the OCD group (Table 2). There was a significant group difference in the activation of PCC (Figure 3C, bottom left; and Table 2). Additional differences between the groups were observed in the cerebellum and putamen (Table 2). There were no significant differences within brain regions outside of our a priori ROI.
This and all subsequent analyses were limited to the OCD group. Neural activation in several brain regions in the OCD group correlated with symptom severity as measured by the YBOCS during extinction recall. Four patients with OCD were removed from this analysis owing to either excessive movement (>3 mm, 1 patient) or insufficient SCRs (3 patients), leaving a total of 17 patients with OCD analyzed. A number of our a priori regions exhibited significant activation in the contrast eCS+E > eCS+NE that was positively correlated with YBOCS scores. These regions included the vmPFC, cerebellum, and PCC (Figure 4A and Table 3). Additionally, activations in several other regions were negatively correlated with YBOCS scores, namely, the dACC and the insular cortex (Figure 4A and Table 3). No significant activations or deactivations were found outside of our a priori ROI. Regression plots for all the previously mentioned regions are shown in eFigure 2A.
We also examined whether neural activation in patients during recall (eCS+E>eCS+NE) was correlated with the ability to recall extinction in the OCD group (ie, ERI scores). The pattern of significantly correlated activation in these analyses revealed similar patterns or results to that of the YBOCS: ERI was positively correlated with activations in the vmPFC, cerebellum, and PCC (Figure 5A and Table 3) and negatively correlated with the dACC and the insula (Figure 5A and Table 3). No significant correlations outside of our a priori ROI were found. Regression plots for all the previously mentioned regions are shown in eFigure 2B.
While a distinct pattern of correlations between the YBOCS and ERI and extinction-induced activations was noted, the correlations between these 2 measures and extinction-induced activations overlapped in 5 brain regions, namely, the vmPFC, cerebellum, PCC, dACC, and insula cortex (eTable 2). Given the high correlations observed, we sought to examine the potential influence/contribution of each of these 5 brain regions to both YBOCS and ERI values using a stepwise regression analysis.
The first stepwise regression examined the additional value of these 5 brain regions (independent variables = vmPFC, cerebellum, PCC, dACC, and insula) in the ability to predict OCD symptom severity (dependent variable = YBOCS). In step 1, cerebellum was entered into the equation as an independent variable (r2 = 0.69; F1, 15 = 32.67; P < .001) with an intercept value of 22.29 and a β of 0.83. In step 2, insula was added to the equation as an independent variable, significantly increasing and contributing to the ability to predict symptom severity (r2 = 0.85; F2, 14 = 40.99; P < .001), with an intercept of 22.30 and β values of 0.60 (cerebellum) and −0.47 (insula; Figure 4B). Addition of vmPFC, PCC, and dACC did not significantly improve the R2 value, suggesting that while all the activations during recall in all 5 brain regions are highly correlated with the YBOCS, the most significant contributors to the symptom severity were activations in the cerebellum and insular cortex. The robustness of these results was tested with forward and backward regressions. Forward regression methods confirmed the same results, while backward regression (which can lack power and result in large standard errors if substantial multicollinearity exists), resulted in the inclusion of the cerebellum, dACC, and PCC as independent variables.
The second stepwise regression examined the additional value of the same brain regions in the ability to predict extinction retention. In step 1, the cerebellum was entered into the equation as an independent variable (r2 = 0.72; F1, 15 = 39.69; P < .001) with an intercept of 37.47 and a β of 0.85. In step 2, the dACC was added to the equation as an independent variable, significantly increasing and contributing to the ability to predict ERI (r2 = 0.84; F2, 14 = 38.74; P < .001) with an intercept of 42.23 and β values of 0.69 (cerebellum) and −0.38 (dACC; Figure 5B). Addition of the vmPFC, PCC, and insula cortex did not significantly improve the R2, suggesting again that the most significant contributors to ERI are activations in the dACC and cerebellum. Forward and backward regression methods confirmed the final model obtained using stepwise selection.
We examined the relationship between ERI and OCD symptom severity. This analysis revealed that the higher the ERI, the worse the OCD symptoms (r = 0.56, P < .05, n = 18; Figure 6). These results are consistent with the counterintuitive results previously stated, in which the higher the activations in brain regions involved in fear extinction, the worse the OCD symptom severity.
Quiz Ref IDIn this study, we demonstrated that while the expression of conditioned fear and its subsequent extinction is intact (as measured by SCR), the recall of the extinction memory is impaired in patients with OCD. We observed decreased activation of the vmPFC across all experimental phases in patients with OCD relative to control subjects. In addition, blunted responses within the hippocampus and caudate were observed during the fear conditioning phase, as well as within the cerebellum, PCC, and putamen during the extinction recall phase in the patients with OCD. Stepwise regression analysis showed that the activations of the cerebellum and insular cortex during extinction recall were the most significant predictors of the variance observed in symptom severity in patients with OCD. Lastly, our data showed a paradoxical relationship between ERI, vmPFC, and dACC activations during extinction recall and OCD symptom severity. That is, the higher extinction retention values, and hence increased vmPFC and decreased dACC activations during extinction recall, the more severe the OCD symptoms. Quiz Ref IDA number of studies have highlighted the role of the amygdala in fear acquisition and extinction and as a brain region that contributes to the psychopathology of anxiety disorders. However, we did not observe abnormal amygdala responses at any phase of the experiment in patients with OCD, further suggesting that this brain region may not be a key contributor to OCD pathophysiology within the context of fear conditioning and extinction.
The hippocampus and caudate have been previously implicated in the acquisition of conditioned fear in rodents and in humans.35 Striatal functioning has been shown to track fear conditioning and reversal of conditioned fear responses in healthy humans.36 Lesions of the dorsal striatum in rodents have been shown to impair auditory fear conditioning,37 and hippocampal function is critical for contextual fear conditioning and for the expression of context-specific fear extinction memories.38,39 Aberrant functional activation of the caudate is one of the most consistent findings in the neuroimaging literature of OCD (reviewed in the article by Milad and Rauch1). Structural and functional abnormalities in the hippocampus have also been previously reported in OCD.40,41 Therefore, the blunted responses of these brain regions during fear conditioning (in the absence of psychophysiological differences) in the OCD group may represent abnormal encoding of the associative learning needed to form fear memories in OCD, which may be related to the inflexibility to switch between fear and safety learning. Our data suggest that there may be differences in the neural networks expressing the peripheral measures of the conditioned fear and those involving the encoding of the fear memory per se. For example, it has been shown that the dACC, insular cortex, and other brainstem regions are key areas involved in the expression of conditioned responses in humans.6,42,43 In the present study, we observed comparable activations in these brain regions in the 2 groups studied, supporting the lack of between-group differences at the psychophysiological level. Thus, the abnormal function within the caudate and hippocampus in OCD during the fear conditioning phase may be related to abnormal consolidation of the associative fear memory and not so much in its expression. However, an alternative explanation is that our skin conductance measure was not as sensitive as our imaging indices in detecting between-group differences in this task.
During fear extinction, we observed extinction-associated deficits in patients with OCD in a locus within the prefrontal cortex observed in this study that is distinct from the commonly reported hyperactivation of more lateral orbitofrontal cortical regions in OCD. The abnormal function of this vmPFC region in OCD has been previously reported when subjects with OCD undergo a different behavioral paradigm (error detection).44 The impaired fear extinction recall and blunted vmPFC activation during extinction recall in the OCD group examined is comparable to data in patients with PTSD and schizophrenia.13,45,46 Another common element between the 2 disorders is the aberrant putamen activation. The functional abnormality we observed in the putamen during extinction recall in OCD is consistent with the involvement of this brain region in fear conditioning and emotion regulation and has also been previously implicated in the pathophysiology of OCD.1 We have shown that the putamen exhibits increased activation to conditioned and unconditioned cues to fear acquisition and has been shown to exhibit dysfunctional responses in patients with PTSD undergoing fear conditioning.5 The abnormal responses of the putamen, together with that observed in the PCC, also distinguish the functional deficits during extinction recall in OCD from PTSD, the latter exhibiting deficits in the dACC and hippocampus instead. Thus, while there are common dysfunctions between OCD and PTSD, there are many differences in abnormal responsivity within the context of fear learning and extinction that highlight the distinct neural correlates associated with the 2 disorders.
Quiz Ref IDWithin the vmPFC, we observed reduced activation in the patients with OCD during extinction recall. However, others have reported error-related hyperactivation of the vmPFC in patients with OCD.47,48 Previous positron emission tomography studies have shown increased resting metabolic activity within the adjacent OFC (more ventral and lateral regions) that was associated with symptom provocation and severity in patients with OCD.49,50 One factor that may be contributing to differences in vmPFC activation observed in our study and those observed by others is that fMRI is the use of different behavioral tasks. For example, Fitzgerald et al48 used error-related monitoring task, which is arguably a more cognitive task when compared with the experimental task used in our study. Another factor is that in measuring activation (ie, relative activity), fMRI does not account for differences in baseline activity. Thus, the diminished regional activation in OCD observed in this study could be a consequence of higher baseline activity. This is especially germane, as resting state studies of OCD using positron emission tomography with 18fluorodeoxyglucose have typically found elevated activity in the OFC, striatum, and ACC. Although there may be an apparent inconsistency as to whether the vmPFC/OFC is hypoactive or hyperactive in patients with OCD, our results, together with those from positron emission tomography and previous fMRI studies, suggest that lateral and medial portions of the OFC are dysfunctional in OCD.
The cerebellum plays a role in processing fear memories51 and has been implicated in the extinction of eye-blink conditioning.52 We have previously reported significant increase in cerebellum activation during extinction recall in healthy humans.10,28 In OCD, both structural and functional abnormalities in this brain region have been previously reported and have been linked to symptom severity. For example, reduced cerebellar functional responsivity in a Stroop task has been reported in OCD, and that cognitive behavioral therapy resulted in the normalization of this impairment.53 Structural and functional abnormalities within the cerebellum have been reported in OCD and Tourette syndrome and have been associated with increased severity in tic and OCD symptoms as well as motor disinhibition.54,55 In the present study, the blunted response in the cerebellum observed in patients with OCD is consistent with its potential role in the psychopathology of OCD. Additional studies are needed to further explore the role of the cerebellum in this disorder.
While we did not observe any between-group differences in the functional activation of the insular cortex or the dACC, activation of both structures during extinction recall, along with the vmPFC, PCC, and cerebellum, was correlated with both magnitude of extinction recall and symptom severity in patients with OCD. One unanticipated result from our stepwise regression analysis was that functional responses within the vmPFC during recall was not one of the key predictors of OCD symptoms or extinction retention. Instead, our results showed that the insular cortex and cerebellum were key predictors of OCD symptom severity, and the dACC and cerebellum were significant predictors of the extinction memory recall in patients with OCD. As just noted, these analyses further highlight the potential role of the cerebellum in the pathophysiology of OCD. The involvement of the insular cortex and dACC as significant predictors of YBOCS and extinction scores may be related to the expression of fear and arousal associated/indexed by these measures. For example, the role of the insular cortex in interoceptive processing is well documented.56 Thus, the significant contribution of the insular cortex to variance in YBOCS and extinction retention scores may be related to differences in interoceptive processing.57
We predicted that deficient extinction in patients with OCD would be inversely correlated with the YBOCS scores. We also predicted that vmPFC dysfunction would be inversely correlated with symptom severity. Our data showed that the better the extinction retention, the worse the OCD symptom severity. Moreover, more activation of the vmPFC (and less dACC) correlated with worse OCD symptoms. We conducted the same correlations with the subscales of OCD (obsessions alone and compulsions alone) and again the same finding was observed (data not shown). One possible explanation for these unexpected, and perhaps paradoxical data, is that patients with worse, or more elevated OCD symptoms, could have developed coping/avoidance mechanisms when facing aversive or unwanted stimuli. If the patients are able to avoid, fear toward the aversive stimuli is reduced.
Quiz Ref IDStudies have now shown that OCD treatment with D-cycloserine enhances the efficacy of cognitive behavioral therapy in patients with OCD,58,59 although some investigators did not observe this effect.60 D-cycloserine has been shown to facilitate fear extinction in rodents via its effects on N -methyl-D-aspartate receptors.61 It has been suggested that the clinical improvement observed with D-cycloserine use in OCD may be owing to enhancing extinction mechanisms,59 but deficits in extinction in this clinical population have not been previously noted. Our data showed that extinction retention is deficient in patients with OCD, yet the correlation between OCD symptom severity and the magnitude of fear extinction was not in the expected direction. This raises an important point, which is that there may be additional factors or variables in patients with OCD that may contribute to or correlate with deficient fear extinction. Additional studies investigating different subtypes of OCD with larger sample sizes may help elucidate some of these factors and begin to examine how D-cycloserine may modulate de novo extinction capacity in patients with OCD.
Correspondence: Mohammed R. Milad, PhD, Department of Psychiatry, Harvard Medical School and Massachusetts General Hospital, 149 13th St, CNY 2518, Charlestown, MA 02129 (firstname.lastname@example.com).
Submitted for Publication: June 15, 2012; final revision received September 19, 2012; accepted September 28, 2012.
Published Online: April 17, 2013. doi:10.1001/jamapsychiatry.2013.914
Conflict of Interest Disclosures: Dr Rauch participates in research funded by Cyberonics and Medtronic. Dr Wilhelm receives research funding from the National Institutes of Health. She also receives royalties from Oxford University Press, New Harbinger Publications, and Guilford Publications. Dr Wilhelm receives support in the form of free medication and matching placebo from Forest Laboratories for a clinical trial funded by the National Institutes of Health. She has also received speaking honoraria from various academic institutions.
Funding/Support: This work was supported by funding from the Judah Foundation to Dr Milad. The project described was also supported by Conte Center (principal investigator: Suzanne Haber) grant MH086400 to Dr Milad.
Previous Presentations: This study was presented in part as posters at the Gordon Research Conference: Amygdala in Health and Disease; August 2, 2011; Waterville, Maine; and at the Society for Neuroscience Annual Conference; November 13, 2011; Washington, DC.
Additional Contributions: We thank Daria Boratyn, BA, for technical assistance during the revision process of the article.


text: Customer Commitment The biggest hurdle some retailers face when implementing a loyalty program is getting customers to notice the many benefits. When Mid-State Petroleum launched its loyalty offering last November company Vice President Tony Perez launched a promotion to give away $10,000 in rewards at each of his locations. New customers received a $5 reward

subset: commoncrawl


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Image: Life cycle sketch of Spilosoma canescens (Butler)
Composite sketch by Alexander Walker Scott of the life cycle of Spilosoma canescens, numbers 10 and 11 in the Scott family's first notebook (page 4), dated January and February 1839. AMS563/317.
This sketch would have been a reference for the finished painting of this species made much later by Harriet Scott for possible inclusion in her father's Lepidoptera publication (one of 4 species in plate number AMS193/69).
The annotations on this sketch are AW Scott's references to his notebook, where he would record more observations. Some excerpts follow:
"No.10. Chrysalis of a very hairy brown caterpillar with an orange stripe down the back - caterpillar eat of the Dock, Cabbage and Canterbury Bell leaves - Chrysalis black brown and small - turned to the above state 24 Janry 1839, and was placed in bran.
No.11 Moth of the above on the 5th February 1839 - Drawing exact size. Body, Saturnine red with black spots at the joints - white at the end..."
- Creator:
- Alexander Walker Scott
- Rights:
- © Australian Museum Archives
An example from the collection of butterfly and moth sketches made by AW Scott and his daughters over a period of nearly 30 years, beginning in the late 1830's, when AW Scott and his stepdaughters Frances and Mary began recording their observations of moths and butterflies.
With the family's move to Ash Island, the project continued and eventually Scott's younger daughters Helena and Harriet joined in. Many of the sketches were used as a starting point for the beautiful plates created by Helena and Harriet for their father's published work on Lepidoptera.
Last Updated:


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PEMBROKE PINES, Fla. - Pembroke Pines Police are looking for a man who was last seen at his home early Tuesday. Family members believe he is depressed.
Marc Tecosky, 57, was last seen in the 12000 block of NW 15th Street in Pembroke Pines about 8 a.m. Tuesday.
Tecosky is described as 5 feet 10 inches tall and 150 pounds. He has brown hair, blue eyes, and a mustache.
He was last seen driving a blue 2000 four-door Honda Accord with Florida tag ASNF54.
Anyone with information is asked to call police at 954-431-2200.
Copyright 2013 by Local10.com. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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StartUpHire is the place to find Marketing jobs in and near Redwood Shores. Review the list of Marketing Redwood Shores career opportunities to the left. These Marketing jobs represent some of the most rewarding careers available.
You can refine your job search for Marketing career opportunities in Redwood Shores by adding a job title, company name, or keyword to the search box above … or click the "Advanced Search" link for more options.
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Don't miss out on a lower price on this hotel
Get an overview of this hotel3-star hotel with free airport shuttle and restaurant
Popular property highlights
Situated in a state park, this hotel is within a 15-minute walk of Utah Valley Convention Center and Reed Smoot House. Lavell Edwards Stadium and Peaks Ice Arena are also within 1 mi (2 km).
Hotel Features
Along with a restaurant, this smoke-free hotel has an indoor pool and an outdoor pool. Free WiFi in public areas, free self parking, and a free airport shuttle are also provided. Additionally, a fitness center, a bar/lounge, and a coffee shop/café are onsite.
Room Amenities
All 330 rooms offer WiFi, room service, and flat-screen TVs with cable channels. Guests will also find wired Internet, premium bedding, and coffee makers.
Guest Highlights
- Good location
- Breakfast
- Helpful staff
- Clean guestrooms
Provo Marriott Hotel & Conference Center
Hotel Amenities
Hotel Amenities
In addition to an indoor pool and an outdoor pool, Provo Marriott Hotel & Conference Center provides a spa tub and a sauna. The hotel offers a restaurant, a coffee shop/café, and a snack bar/deli. A bar/lounge is on site where guests can unwind with a drink. Public areas are equipped with complimentary wireless Internet access.
Business-related amenities at this 3-star property consist of a business center and meeting rooms. Event facilities measuring 27987 square feet (2600 square meters) include a conference center. This business-friendly hotel also offers a fitness center, gift shops/newsstands, and concierge services. A roundtrip airport shuttle is complimentary to guests (available 24 hours). Onsite self parking is complimentary.
Provo Marriott Hotel & Conference Center is a smoke-free property.
- Conference center
- Year Built 1983
- Conference space size (feet) - 27987
- Conference space size (meters) - 2600
- Number of meeting rooms - 21
- Conference space
- Sauna
- Number of floors - 9
- Number of buildings/towers - 2
- Free airport transportation
- Concierge services
- Fitness facilities
- Bar/lounge
- Coffee shop or café
- Business center
- Express check-out
- Express check-in
- Dry cleaning/laundry service
- Elevator/lift
- Gift shops or newsstand
- Free WiFi
- Laundry facilities
- Meeting rooms 19
- Total number of rooms - 330
- Restaurant
- Safe-deposit box at front desk
- Snack bar/deli
- Free self parking
- Smoke-free property
- Spa tub
- Indoor pool
- Outdoor pool
- Breakfast available (surcharge)
Family Friendly Amenities
- Family Hotel
- Outdoor pool
- Indoor pool
- Free Wi-Fi
- Snack bar/deli
- Laundry facilities
- Microwave (on request)
- Cribs/infant beds (complimentary)
Available in all rooms: ,
Available in some public areas: Free WiFi
Free self parking
Room Amenities
- Connecting/adjoining rooms available
- Premium TV channels
- Flat-panel TV
- Room service (limited hours)
- Pay movies
- Premium bedding
- Air conditioning
- In-room climate control (air conditioning)
- Free weekday newspaper
- Phone
- Coffee/tea maker
- Microwave (on request)
- Daily housekeeping
- Private bathroom
- Hair dryer
- Shower/tub combination
- Iron/ironing board
- In-room safe
- Desk
- Cable TV service
- Free cribs/infant beds
- Rollaway/extra beds (free)
- WiFi (surcharge)
- Wired Internet access (surcharge)
Where to Eat
Buffet breakfasts are available for a surcharge.
Slate - This restaurant specializes in American cuisine and serves breakfast, lunch, and dinner.
Room service (during limited hours) is available.
Nearby Things to Do
An indoor pool, an outdoor pool, and a spa tub are on site. Other recreational amenities include a sauna and a fitness center.
If you have requests for specific accessibility needs, please note them at check-out when you book your room.
- Accessible bathroom
- Roll-in shower
- In-room accessibility
Hotel Policies
Check-in time starts at 3 PM
Special check-in instructions:
Check-out time is noon
Payment types
Children and extra beds
- Children are welcome.
- Free rollaway/extra beds!
- Free cribs (infant beds)!
- Pets not allowed (service animals welcome)
You need to know
Extra-person charges may apply and vary depending on property policy.
Optional extras
- Fee for buffet breakfast: USD 12 per person (approximately)
- Fee for in-room wireless Internet: USD 9.95 per day (rates may vary)
- Fee for in-room wired Internet: USD 6.95 per 24-hour period (rates may vary)
Hotel Name
- Hotel Provo
- Marriott Hotel Provo
- Marriott Provo
- Marriott Provo Hotel
- Provo Hotel
- Provo Marriott
- Provo Marriott Hotel
- Marriott Provo Hotel Conference Center
We should mention
This property offers transfers from the airport. Guests must contact the property with arrival details before travel, using the contact information on the booking confirmation. The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.


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Where: AMC Burbank Town Center 8, 201 E. Magnolia Blvd. #345, Burbank; and AMC Orange 30 (AMC Block 30), 20 City Blvd. W., Orange
When: For showtimes, go to www.amctheatres.com
"Hours," a small movie starring the late Paul Walker who was killed in a car crash in Valencia on Nov. 30, is being released today in a couple theaters around Los Angeles and on Video on Demand.
Set around a New Orleans hospital, where the power goes out during Hurricane Katrina, Walker's character, Nolan, is given his newborn baby after his wife dies in childbirth. The hospital is being abandoned but the infant needs a ventilator to live, and Nolan spends the movie searching for ways to keep the ventilator going amid the chaos.
A car lover, Walker came to fame as part of the "The Fast and the Furious" franchise, but most of his film career was spent in small indie movies like "Hours" (two others were released this year) where he was able to show his acting rather than driving skills.


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NORTHWEST MIAMI-DADE, Fla. - Police are investigating a fatal shooting in northwest Miami-Dade County.
It happened at Northwest 9th Street and 20th Avenue, police said.
According to authorities, one victim died on the scene. Another person was transported to the hospital, police said. The victim's condition is not yet known.
A witness told Local 10's Janine Stanwood someone at a Halloween party started shooting after a confrontation.
The lieutenant on the scene said there are no suspects in custody, but authorities are getting information from witnesses and actively searching for suspects.
Stay tuned to Local 10 for more on this story.
Copyright 2012 by Post Newsweek. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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Dear friends,
The issue of pride/humility came up in several posts recently. It reminds me of a conversation I had recently with my partner. We were watching the US version of Gordon Ramsay's Kitchen NIghtmares. As usual, it featured an arrogant self-appointed 'chef' who refused to see how he was failing in all aspects of restauranteering, even as he insists, 'I know I'm good!' Because of his stubborn, arrogant ways the restaurant was facing collapse. The failing restaurant was affecting not just the chef but his girlfriend and her family who had been doing what they can to support him and the business. In fact, it was his girlfriend's parents who provided the money for the restaurant. Ramsay confronted the chef and told him that he was being selfish, that he was taking his loved ones for granted. The chef obviously failed to see how he was taking them for granted. If anything, he seemed to think that they were being overly critical of him. It then struck me that the chef was not in the least bit grateful for the support he had from his loved ones. Or at least, he was unable to see how there was much to be grateful for. And this lack of gratitude fed his arrogance, his pride, his refusal to listen to advice.
So I remarked to my partner, 'Can one truly be humble if one doesn't know how to be grateful?' In other words, I wonder if gratitude and humility are really co-dependent, one providing the conditions for the other. This then led me to wonder just how often I've overlooked the simplest things that I ought to be grateful for.
What are your thoughts?
Best wishes,


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Electronic reserves, also called E-Reserves, are placed online and made available through the Muskingum Library catalog. Students can retrieve reserves anytime from any place where they have Internet access. E-Reserves are downloadable and printable.
Electronic reserves can be integrated with Blackboard or any web interface.
Who can put items on E-Reserves?
Participation in e-reserves is open to any instructor at Muskingum University.
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There are no limits to the number of materials that may be placed on e-reserves.
What materials can I place on E-Reserves?
Please see our E-Reserves Policy for full information.
The Library follows the Fair Use provisions from Section 107 of the United States Copyright Act of 1976.
Here are a few examples of items that normally qualify under the Fair Use provisions:
The following materials cannot be placed on e-reserves without obtaining copyright permission and / or paying royalties:
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If an item does not qualify as Fair Use, the library must have permission in the form of a signed letter from the copyright holder. Instructors will be responsible for obtaining copyright permission and for any royalty fees that may be assessed. The library is happy to help instructors through this process, but will not be ultimately responsible for securing copyright.
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Students access them through the E-Reserves link found at the top of every page on the Library's web site.
Students must use the barcode number on their student ID and a course password to access readings. The course password will remain constant throughout the semester, but will change each semester. Please advise students of the password.
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The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.
NOTICE: The Library reserves the right to refuse placing items on electronic reserves that it feels violates the Fair Use provisions without obtaining copyright permission. It also reserves the right to remove items for which the publisher or copyright owner has requested removal.


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Natalie Imbruglia
Hailing from down under, Natalie practically rose form obscurity to fame with her hit song, "Torn" and follow up, "Wishing I Was There."
AppealWhether it's the urban look or the timeless beauty of her face, there is something absolutely appealing about her. It certainly helps that she is gorgeous -- and those pouty lips aren't bad either.
SuccessOne successful album is not enough to establish her as a permanent fixture in the music scene, but all she needs is a few more successful hits to join the company as one of the premier artists of the last 10 years.
Natalie Imbruglia BiographyNatalie Imbruglia's meteoric rise to fame has taken the music industry and the world by surprise. However, it is probably not a surprise to those who knew her in her early days. She was born on February 4 1975, in a small town two hours from Sydney, Australia.
She took tap and ballet lessons as a child and demonstrated her strong will and determination at an early age. She believed in herself and felt she could do anything she set her mind to. Imbruglia credits these years as the source of her strength and perseverance as a woman.
"It taught me discipline and steadfastness", she said in an US magazine interview. "I wasn't that good but I was so determined that I used to put planks of wood down in the garage, and practice and practice. I'd lie in bed at night and work my ankle exercises."
Much to her parent's dismay, Imbruglia then turned her focus to acting and ventured to Sydney to find acting work. She landed several television commercials for Coke, Bubblicious gum, and a snack called Twisties. The more jobs she landed, the more her parents supported her dreams of acting. They soon let her quit the school for performing arts to concentrate on her acting pursuits.
She got a temporary role on the popular Australian soap opera Neighbours, and became an instant success. She was so well received by audiences that the producers decided to make her character permanent.
Her joy, however, was short lived, as she grew tired of the show and eventually left to find more satisfying work. "I was like, what have I done? I'm not saying it was a nasty, terrible job; it just wasn't for me".
She moved to London where she lived in relative obscurity for two years. She did little acting work and became enamored with the London club scene. She refused to use her Neighbours fame to get her ahead in London.
She soon encountered financial difficulty and began writing songs to earn some money. She showed her work to Mark Fox, former Haircut 100 percussionist and current creative director for BMG publishing. Fox, in turn, contacted Phil Thornally, the former bassist for Cure.
The trio proceeded to record "Torn" and got in touch with a high-profile manager named Anne Barrett. She instantly came aboard the Imbruglia train and took "Torn" to its next destination; RCA executive Jeremy Marsh's desk. Marsh was so impressed that he signed Imbruglia immediately.
Torn hit radio waves as an import on an L.A. station and went on to receive widespread airplay. Next came the video to the song, as well as a much publicized appearance on Saturday Night Live. When the full album, Left of the Middle, was finally released in spring of 1998, it debuted at No.10.
It earned her a host of awards, including MTV Music Video Awards, the Australian Record Industry Awards, the MTV Europe Video Music Awards, and the Billboard Music Awards, three 1999 Grammy nominations (Best New Artist, Best Pop Album, and Best Female Pop Vocal Performance), and two Brit Awards for Best International Female and Best International Newcomer.
Imbruglia takes her rise to fame with a grain of salt. "I think it's just [a matter of] trying to concentrate on your little goal in life and not focus on the big picture too much. That's what I try and do". It's also rumored that she dated David Schwimmer of Friends and singer Lenny Kravitz. Watch for her new album scheduled to be in stores later this year.
Show comments


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View Poll Results: What one do you like?
- Voters
- 65. You may not vote on this poll
Results 1 to 5 of 12
June 6th, 2013 01:17 PM #1Member
- Join Date
- Feb 2013
- Posts
- 36
Baby Girl due in a couple of weeks, I think we have it narrowed down to 3...
June 6th, 2013 01:23 PM #3Member
- Join Date
- May 2011
- Posts
- 35
June 6th, 2013 01:29 PM #5Member
- Join Date
- Aug 2011
- Posts
- 77
Callie Rose is superior to the other two, though I would prefer a longer name to get Callie as a nickname.
Makenzie is really trendy and there are so many spelling variants that it bothers me. I think the trend is wearing down, but it will inevitably become a name people associate with the 2000s (much like Lisa is associated with the 1960s-1970s). I don't particularly care for Rae either unless you are honoring someone.
Adalyn Reese is okay, but trendy as well. What about Adeline Rose or Ada Rose?
June 6th, 2013 01:31 PM #7
June 6th, 2013 01:35 PM #9Member
- Join Date
- Feb 2013
- Posts
- 36
Thank you ladies. I do like Adalyn Rose too. We only have Makenzie in the running because my hubby wanted Kenzie by itself and I said no, Rae was what he came up with for a middle name, which he stole that from one of his soldiers. Callie is one we both somewhat agree on. I do agree it is somewhat short but I do not like the longer name options for Callie. I would love also to have a "A" middle name for Callie but the only one I come up with is Ann which I'm not 100% sure if it sounds to choppy.
PS my middle name is Ann my mom's is Rosylynn so Rose kinda works in it for her.


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BCG fosters long-term relationships with a number of today's most relevant organizations, serving as a partner of choice when it matters most and ensuring that our "seat at the table" helps transform the world.
Our global partnerships include investments in the areas of public health, development, education, infrastructure, and the environment.
With the majority of our global partners, we undertake a series of projects each year, tackling the highest priority issues for each organization. With others, we explore issues of shared public interest and advance common causes. We bring to all our global partners the same powerful drive to make a difference.
To bring the best of BCG—our people—to these organizations, we also embed a number of our employees to work as full-time staff members at several of our partner organizations.
Working to help all people lead healthy, productive lives
Bringing together business leaders from G20 economies to develop consensuses around critical issues for businesses
Designing technologies to create a better future for people
Applying business principles to social challenges
Giving children around the world a healthy start in life, the opportunity to learn, and protection from harm
Expanding educational opportunity around the world
Spreading ideas that change attitudes, lives, and ultimately, the world
Fighting hunger worldwide
Improving the state of the world by engaging leaders in partnerships to shape global, regional, and industry agendas
Aiming to deliver innovative solutions that meet the needs of both people and nature


text:
The Federal Government will Become America's Model Employer for the 21st Century.
Recruit, Retain and Honor a World-Class Workforce to Serve the American People.
Find out more about Federal compensation throughout your career and around the world.
Staffing to align with your agency's mission
Review the Federal Employees Group Life Insurance (FEGLI) Handbook
Answering your questions about Healthcare and Insurance
Manage your retirement online.
"...The Director of the Office of Personnel Management shall serve as the Suitability and Credentialing Agent..." ~Executive Order 13467, as amended
"...primary executive branch service provider for background investigations..." ~Executive Order 13467, as amended
OPM's Human Resources Solutions organization can help your agency answer this critically important question.
Developing senior leaders in the U.S. Government through Leadership for a Democratic Society, Custom Programs and Interagency Courses.
Visit this federal site to search for our regulatory notices, proposed and final rules.
See the latest tweets on our Twitter feed, like our Facebook pages, watch our YouTube videos, and page through our Flickr photos.
Chapter 43 of title 5, United States Code, provides for performance management for the Senior Executive Service (SES), the establishment of SES performance appraisal systems, and appraisal of senior executive performance. Agencies establish performance management systems that hold senior executives accountable for their individual and organizational performance in order to improve the overall performance of Government by:
Agencies develop performance management systems subject to OPM regulations and approval.
The supervisor establishes performance elements and requirements in consultation with the executive and consistent with the goals and performance expectations in the agency's strategic planning initiatives. The supervisor proposes the initial summary rating, based on both individual and organizational performance, and taking into account customer satisfaction and employee perspective.
The executive's initial summary rating is reviewed by a Performance Review Board (PRB). The agency head (or his/her designee) determines the executive's annual summary rating.
Agencies develop performance management systems subject to OPM regulations and approval. Agency systems must contain 5 summary performance levels as follows:
Career SES appointees and certain limited appointees may be suspended for disciplinary reasons, defined as "misconduct, neglect of duty, malfeasance, or failure to accept a directed reassignment or to accompany a position in a transfer of function." Statute states that suspensions must be for more than 14 days. However, an agency may issue a reprimand or admonishment for offenses that do not warrant a suspension. In most cases, the executive must receive 30 days advance notice of a proposed suspension, has the right to reply, and the right to appeal to the Merit Systems Protection Board (MSPB).
The law does not specify procedural requirements for noncareer, most limited term appointees, limited emergency appointees, and reemployed annuitants. Thus, such appointees may be suspended under established agency procedures. Appointees under these circumstances do not have appeal rights to MSPB.
If a career executive is removed during the probationary period for performance reasons, he/she is entitled to placement in a GS-15 position with saved pay (unless appointed to the SES from outside Government or from a noncareer-type appointment). After the probationary period, the executive must be placed in another position within the SES or removed from the SES for one unsatisfactory rating. An executive must be removed from the SES for two unsatisfactory ratings in 5 years, or for two less than fully successful ratings in 3 years. The executive may request an informal hearing before MSPB and is entitled to placement in a GS-15 position with retained pay. No career executive can be removed for performance reasons during 120 days after appointment of a new agency head or new noncareer supervisor with removal authority, except removals based on a rating(s) prior to appointment.
Reduction-in-force (RIF) retention determinations are based primarily on performance. The agency must place an executive who has completed a probationary period in any SES vacancy for which he/she is qualified. If no vacancy exists, OPM has 45 days to try to place the executive elsewhere in the Government. If the executive cannot be placed in the SES, he/she is entitled to placement in the agency at a GS-15 position with saved pay, and has appeal rights to MSPB on agency compliance with competitive RIF procedures.
In lieu of placement in a GS-15 position, the executive may elect discontinued service retirement with 25 years service or 20 years of service at age 50.
Disciplinary removal procedures and rights are similar to those for competitive service employees, except that the standard for action is "misconduct, neglect of duty, malfeasance, or failure to accept a directed reassignment or to accompany a position in a transfer of function." The executive must receive 30 days notice of a proposed removal, has the right to reply, and may appeal to MSPB, but has no placement right to a GS-15 position.
Removal is at the discretion of the agency head. The law does not specify procedural requirements for noncareer, most limited term appointees, limited emergency appointees, and reemployed annuitants. Thus, such appointees may be removed under established agency procedures. Appointees under these circumstances do not have appeal rights to MSPB. Some executives on limited term appointments have placement rights.
OPM - in coordination with OMB - has issued a Governmentwide SES performance appraisal system, designed through the collaboration of an interagency workgroup. The SES appraisal system meets the SES performance management needs of agencies and their SES members - providing a consistent and uniform framework for agencies to communicate expectations and evaluate the performance of SES members, particularly centering on the role and responsibility of SES members to provide executive leadership. Specifically, the SES appraisal system promotes greater consistency, clarity, transferability, and equity in performance standards, the derivation of ratings, and the link to compensation. The SES appraisal system also provides the necessary flexibility and capability for appropriate agency customization.


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Just Who Is The Villain In The 'Ant-Man' Movie?
Rumors abounded last week about just who is going to be the bad guy in Marvel's upcoming Ant-Man movie, the one that stars Paul Rudd and up until about a month ago, was to be directed by Edgar Wright. (Peyton Reed is the new director.)
We've pulled together the scuttlebutt, which you can read all about after the jump. Be warned: There may be spoilers, if this stuff is true.


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NetWellness is a global, community service providing quality, unbiased health information from our partner university faculty. NetWellness is commercial-free and does not accept advertising.
Monday, September 25, 2017
Infectious Diseases
RE: Mononucleosis
My son was diagnosed with mono in September 2005 and spent 5 weeks of down time, until blood tests indicated he could continue with hockey at a competitive level. Then throughout April, May and June of this year he has experienced periods of fatigue and low grade fevers.
Recently he is feeling unwell with sore throat, bumps on his tongue, occasional night sweats and fatigue and a cough. Is it possible that a person can relapse with mono or once you have it are you immune? Could he be suffering from a chronic illness due to that virus?
Infectious mononucleosis is caused by Epstein-Barr virus (EBV) which is a member of the herpes virus family. Most of the herpes viruses cause latent infections and, as such, have the potential for relapse. For example, you are probably familiar with "cold sores" caused by herpes simplex virus. These will often return repeatedly during a person's life time. It has been suggested that EBV may be responsible for recurrent fatigue in young and middle-aged adults in an illness known as "chronic fatigue syndrome." Rigorous scientific studies, however, have failed to show a real link between EBV and this illness. Most individuals only have acute mononucleosis once.
Rarely, EBV can cause ongoing and persistent infections. This is a condition that can be diagnosed through further laboratory testing. Furthermore, there are may be many other causes of your son's symptoms. If these symptoms persist you should have him reevaluated by your personal physician. If there are concerns about recurrent EBV or other infections, a consultation with an infectious diseases specialist would be advisable.
Kurt B Stevenson, MD, MPH
Professor of Infectious Diseases
College of Medicine
The Ohio State University


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Beauty Beatbox
No longer available
- Overview
Pump up the volume on your beauty routine. This leather-bound box has a spot for all of your makeup and jewelry, plus it comes with speakers and an MP3 plug-in so you can rock out while you get ready to go out.
- 11" wide x 16" deep x 7" high
- Expertly wrapped in bonded leather.
- Features a mirror, speakers and a 6.3mm jack for connecting your audio device.
- Features a convenient handle and lock for easy mobility.
- Dimensions + Care
- 11" wide x 16" deep x 7" high
Interior Compartments
- Small (2): 3" wide x 2.25" deep x 2.5" high
- Medium: 3.75" wide x 5" deep x 2.5" high
- Large: 8.75" wide x 5" deep x 2.5" high
- Extra Large: 15" wide x 4" deep x 2.5" high
- Wipe with a soft, dry cloth.
- Shipping Info
This item will arrive in 3-5 business days. Please proceed to the Payment & Review page of Checkout for a precise delivery estimate.


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Applying online is as easy as 1-2-3. You can apply now in as little as 20 minutes.
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RESIDENTS in southern Winchester are invited to meet police next week.
Police and partners are holding a community meeting for Stanmore, Badger Farm, Oliver's Battery and St Cross on Monday, December 17.
The Partnership and Communities Together (PACT) meeting starts at 7.15pm at The Carroll Centre in Somers Close, Stanmore.
All residents are welcome to attend and meet the local Safer Neighbourhood Team to discuss any issues affecting the area.


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This game was classified by the community with the following category scores - Violence=1/3, Sex=0/3, Mature Content=0/3. Return to Mars in command of the Curiosity Rover II in a mission to save NASA. Raid the ancient Martian pyramids to gain treasure to shore up the space program's budget in this classic arcade style game. Features high score saving.
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text: BYU's basketball team had a hard, intense practice on Wednesday afternoon, and star senior forward Brandon Davies was out there the whole time, running, rebounding and doing all that was asked of him. That's good news for the Cougars, who watched Davies hobble off the court with about 12 minutes remaining in the 97-71 win over Virginia Tech with a high ankle sprain. "It is making progress. It feels 100 times better than it did. We are finally getting the swelling out of it. It is a day-by-day thing, but it is feeling a lot better," Davies told us after practice, his foot in a plastic garbage can filled with ice and water. Davies said Wednesday marked his first full practice, and that he fully intends to play on Thursday night as the Cougars play host to Loyola Marymount at the Marriott Center (7 p.m., BYUtv). "Today I was able to go full time, which is a good sign, without hardly any pain. Just keep progressing and we are going to be good," he said. "If it keeps getting better every day, as it has been, each day there is a lot of progress I have been making. So tomorrow I hope it feels even better and so I will be able to go." Coach Dave Rose said Davies looked OK in practice, but acknowledged there were some worrisome moments immediately after Saturday's game. "He practiced today, and it has progressively felt better each day, and hopefully it feels good tomorrow. He didn't do a lot yesterday, but he made strides. He practiced pretty good today, so hopefully it feels good tomorrow and we can count on him," Rose said. Davies said he just "came down funny" on the ankle against the Hokies. "I think I got bumped a little bit in the air," he said. "It was a basketball play, and it happens all the time. I just kind of rolled it over. Didn't feel a pop or anything, so it was just one of those freaky type situations." Wednesday, Bronson Kaufusi practiced again with the basketball team and is gradually looking more and more like a basketball player and less like a football player, according to a couple of teammates. Kaufusi could be in uniform on Thursday night if the jersey that has been ordered for him arrives in time. It is not clear yet whether he will appear in a game or not. Probably not, unless the Cougars get out to a big lead. His father, defensive line coach Steve Kaufusi, watched the practice from a couple rows up along with Ralph Haws, Tyler Haws' grandfather. I'll have more comments on Thursday's game in this space tomorrow, but Davies said revenge is definitely on the Cougars' minds after LMU beat them at the Marriott Center last year. "This is our biggest game of the year, right here. It is our first conference game; we got to start it off right. I am pushing myself, and the coaches are pushing me to do everything I can to get back out there," Davies said. "Definitely [a revenge game]. We are fired up for it. They came into our place and got us, and that hit us deep. You are going to see some fire in us tomorrow." Rose said the Lions (7-6) are similar to last year's team that won easily in Provo. "They are very athletic. They rebound the ball well, and it is a really good three-point shooting team. They got four guys that shoot over 40 percent from the three-point line. But defensively is where they really impress me. They are a really physical team that gives great help. It is hard to get an easy basket against them. They make you earn your points," Rose said.


text: Greenbrier delegate named to Board of Education By Mackenzie Mays December 10, 2012 Story Share CHARLESTON, W.Va. -- Delegate Tom Campbell, D-Greenbrier, will become the newest member of the state Board of Education, pending confirmation by the state Senate.Gov. Earl Ray Tomblin appointed Campbell, a former Education Committee chairman, on Monday effective immediately.Campbell, 51, is retiring from the Legislature after serving 16 years in the House of Delegates. He most recently served as the vice chairman of the House Finance Committee and also worked on the education subcommittee."I'm excited and grateful for this appointment. Education has become more of a passion of mine the more I've been around our young people. I want to make a difference in young people's lives, and ultimately the state as a whole, economically," Campbell said."We have great educators and great students, but we need to get deeper. We need to get more people educated and more people prepared for life when they leave their public education."I have talked to the board president [Wade Linger] briefly, but it sounds like the board is committed to having a vision to make that happen," he said.Campbell, an accountant and the chief financial officer of Carson Associates Inc., in Lewisburg, is replacing former board member Lowell Johnson, whose term expired Nov. 4. State Board of Education members serve nine-year terms.Campbell also represented West Virginia on the Southern Regional Education Board and has worked with the Read Aloud program for 15 years.Campbell enters the Board of Education at a controversial time. Since the board voted to fire state Superintendent of Schools Jorea Marple last month, its members and their actions have been under fire. A sweeping efficiency audit of the public school system, now underway, has also been at the center of state education talk, with the board pushing for major changes to the system.The scrutiny is not a concern for Campbell though."I'm used to it. Being in the Legislature, you're used to working amid turmoil. These are some interesting times for West Virginia education, and I'm used to dealing with challenges," he said. "The whole board has to work together. There's got to be teamwork."I'm sure there will be disagreements, but having a chance to influence a child's education, well there's nothing more important than that," he said.Campbell, who received a bachelor of science degree in business administration from West Virginia University in 1983, hopes to focus his work on the board on getting more students prepared for college and the work force. "I think West Virginia has made some great strides nationally in a lot of areas. Education is an area we can really help the state shine in," he said. "We don't just have challenges in the West Virginia school system -- it's a national challenge. I'm hoping we can lead the nation in this."It's a new day in education, not just with technology, but in households and in ways of life. I look forward to trying to help prepare students for life and to do not only what's good for them, but good for the state and good for the country," Campbell said. "I'm not saying that it's going to be easy, but I look forward to helping prepare young people for life."Tomblin released a statement Monday afternoon saying he's confident that Campbell's presence on the board will make a difference."The education of our young people is essential to West Virginia's future and remains one of my top priorities," Tomblin said. "I've worked with Tom for many years, and I'm pleased he will be joining the state Board of Education. I am confident, with his vast knowledge and experience, Tom will be a tremendous asset to our state board."Campbell plans to attend the Board of Education meeting in Lincoln County on Wednesday. The meeting is at Lincoln County High School in Hamlin at 10:30 a.m.Reach Mackenzie Mays at firstname.lastname@example.com or 304-348-4814. Story Share Story Share Trending Now 1 City of Milton tries to revive Morris Memorial property 2 Mitch Vingle: WVU's Lyons watching bombshell merger news 3 Former Boone school board members indicted 4 Morgantown coal operator Laurita indicted in alleged campaign finance scheme 5 Consultant says Yeager Airport needs to extend runway For robbery, murder plot, judge adds 6 years to Lester's term Previous Story Higher ed panel pushes schools to boost college prep Next Story


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While it is very sad the Michael Scott will be leaving Scranton, I am extremely excited to see what the do with Will Ferrell on the show.EXCLUSIVE: Will Ferrell has committed to a four-episode arc on NBC's comedy The Office. He will play a branch manager who comes from the home office and is just as inappropriate as Steve Carell's Michael Scott character. NBC is still figuring out exactly when the episodes will air, but Ferrell has committed to one episode beyond Carells finale, to help create a bridge.
Ferrell called the producers, offering his services because he's a fan and wanted to commemorate Carells swan song by taking part in The Office star's seventh and final season on the show. Ferrell and Carell are close friends who co-starred in Anchorman: The Legend of Ron Burgundy. The stint brings Ferrell back to NBC, where he launched his career on Saturday Night Live. Additionally, he has done arcs on such series as NBC's 30 Rock and HBO's Eastbound & Down, which he also produces.
We found Steve Carell when he was nothing but a movie star and we turned him into a television star, said The Office exec producer Paul Lieberstein (who doubles as the annoying Dunder Mifflin HR executive Toby Flenderson, Michael Scotts arch-nemesis. We are proud to continue The Offices tradition of discovering famous talent, and we hope that once America gets a good look at Will, theyll see what we see, tremendous raw sexuality.


text: Things to do Sunday, Oct. 14, 2012 October 13, 2012 Story Share MusicMEMORIAL GOSPEL SING: 3 p.m. Free, with donations accepted for MADD. In memory of Shannon Brown. Emmanuel Baptist Church, 1401 Washington St. W. Call 304-757-0775.MONTCLAIRE STRING QUARTET: 3 p.m. Adults $12, students and children $6. "Miniatures" features pieces by Mendelssohn, Tchaikovsky, Bridge, Shostakovich, Kirchner, Turina, Ives, Ljova and Piazzolla. Erma Byrd Gallery, University of Charleston. Visit www.wvsymphony.org.DAVID HIGGS ORGAN RECITAL: 3 p.m., Sunday at Sacred Heart Co-Cathedral, corner of Leon Sullivan Way and Virginia Street East. Higgs will play the newly installed Schantz organ. Reception follows in Sacred Heart gymnasium. Call 304-342-8175.Stage/theater"PETER PAN": 2 p.m. Adults $12, students 17 and younger $10. Presented by The Children's Theater of Charleston. Directed by Tara Phares-Pauley. Civic Center Little Theater. Call 304-346-0164.WAYNE BRADY: 8 p.m. Tickets $25, $35 and $45. Multi-talented performer entertains with Improv comedy show. Clay Center. Call 304-561-3570 or visit www.theclaycenter.org.Fairs/festivalsBLACK WALNUT FESTIVAL: 10 a.m. Free admission. Live music, exhibits, contests and carnival. Downtown Spencer, Roane County.Call 304-927-1640. WEST VIRGINIA BOOK FESTIVAL: 12:30 p.m. Free admission. Book Sale, Marketplace and panel discussions featuring authors. Charleston Civic Center. Call 304-343-4646 ext. 287.Karaoke/DJsSLIGHTLY STOOPID: 7 p.m. Tickets $33. The Metropolitan Theater, Morgantown. Call 800-745-3000.Etc.CAPITAL CITY PUNISHMENT: 4 p.m. Adults $15, youth 12 and younger $5, younger than 2 free. Chemical Valley Rollergirls vs. Greenbrier Valley Roller Vixens. Charleston Civic Center. Call 800-745-3000. Visit www.chemicalvalleyrollergirls.com.KANAWHA TRAIL CLUB HIKE: Several different hikes offered. Meet at 1:30 p.m. to carpool from Ohio and Randolph streets. Pick-A-Hike/Pick-A-Leader. Film"POLTERGEIST": 4 p.m. Tickets $5. Rated PG. Flashback Film Series at Park Place Stadium Cinemas, 600 Washington St. E. Call 304-345-6541 or visit www.ourshowtimes.com. Story Share Story Share Trending Now 1 Facebook founder visits Cabin Creek Health Systems 2 Teen pleads guilty to voluntary manslaughter in Oakes Field shooting 3 Huggins, WVU tap South Florida hoops talent 4 Safety shutoff disabled prior to June coal-mining death, report says 5 New company planning $73M synthetic fuel plant in Greenbrier County Statehouse beat: Gubernatorial debate quite a debacle Previous Story Skydiver lands smoothly after daring 24-mile leap Next Story


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2011 Hershey Track and Field Games Results
Neighborhood and Community Services is pleased to announce the results of the 2011 Hershey Track and Field Games which were held at Falls Church High School on May 20 and May 21. Please click on the events below to view the results.
Congratulations to everyone who participated this year. We look forward to seeing you again next year!
For more information, please call 703-324-5533, TTY 711.
Fairfax County is committed to nondiscrimination on the basis of disability in all county programs, services and activities. Reasonable accommodations will be provided upon request. For more information, call 703-324-4600, TTY 711.


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Buffett's Sins of Omission
What price can you put on loyalty? How about more than $600 million over a span of not quite eight-and-a-half years? What if you were playing with other people's money? Perhaps our own Doug Kass should have considered asking those questions at Berkshire Hathaway's (BRK.A, BRK.B) annual meeting last week.
The trade in question is the one that was never made, the sale of BRK's 1.728 million shares of Washington Post (WPO). Both major business units, newspapers and for-profit education, are in seriously impaired industries. Washington Post shares hit an all-time peak of $999.50 on Dec. 30, 2004. Berkshire's stake was worth more than $1.72 billion at the time....284 more words left in this article. To read them, just click below and try Real Money FREE for 14 days.
There's no substitute for a trading floor to get great ideas, so Jim Cramer created a better one at Real Money and blogs there exclusively. We then added legendary hedge fund manager, Doug Kass, with his exclusive Daily Diary and best investing ideas. Staffed with more than 4 dozen investing pros, money managers, journalists and analysts, Real Money Pro gives you a flood of opinions, analysis and actionable trading advice found nowhere else, and allows you to interact directly with each expert.
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SANTA CLARA -- Coach Jim Harbaugh made it abundantly clear Monday that there won't be another kicking controversy between now and the Super Bowl.
"The decision has been made: David Akers is our kicker," Harbaugh said at his weekly news conference.
Harbaugh said the same thing Jan. 10, two days before the 49ers played the Green Bay Packers in an NFC Divisional Playoff game at Candlestick Park.
Akers validated that decision by converting a 36-yard field goal against the Packers in his lone attempt. However, Akers missed from 38 yards against the Atlanta Falcons on Sunday in the NFC Championship game on his only attempt. Akers' kick veered left and hit the top of the upright.
There's no telling if Harbaugh's decision was influenced by the 49ers not being able to re-sign Billy Cundiff, who competed with Akers to kick in the postseason during the two-week break between the end of the regular season and the Packers game.
League rules stipulate that players cut during the postseason can't sign with another team until after the Super Bowl. The 49ers waived Cundiff on Friday, the day they departed for Atlanta. He had signed with the 49ers on Jan. 1 and spent a week or so competing with Akers for the kicking job.
Akers is 30 for 44 on field-goal attempts in 18 games this season. Harbaugh watched Akers kick before the Falcons game and liked what he saw.
"He had an outstanding pregame," Harbaugh said. "He was hitting the ball really well."
Akers struck the ball well on the kick he missed against the Falcons, but it hooked left and struck the upright.
"It's a game of inches, one way or the other," Akers said after the Falcons game. "I struck the ball well, and it clangs on top of the goal post. If you figure that one out, let me know."
When asked if he expects to kick in the Super Bowl, Akers said: "I'm here until they tell me otherwise."