g. a child, someone related to the ambulance crew, someone who sustained gruesome injuries or died), the situation (e.g. danger to ambulance personnel, problems with how the call was relayed), and the EMT/paramedic’s personal response (e.g. feeling helpless) [2-5]. These lists suggest that EMT/paramedics may be able to identify the types of situations that cause acute distress. However, the tantalizing question remains: which acutely stressful CAL-101 cost incidents result in ongoing symptoms and impaired functioning? Inhibitors,research,lifescience,medical Work stress, including the effects

of critical incidents, burdens EMT/paramedics and their organizations, and may interfere with patient care. Posttraumatic Stress Disorder (PTSD) Inhibitors,research,lifescience,medical is often associated

with EMT/paramedics’ critical incidents and is found in 12% to 20% of EMT/paramedics compared to a community prevalence of 1-3% [6]. Burnout, depression and anxiety have also been attributed to critical incidents [5]. These syndromes likely contribute to EMT/paramedics’ high sickness-absence rates compared to other health professions [7]. There is also evidence that acute stress in EMT/paramedics increases medical errors [8]. It would be useful to quickly Inhibitors,research,lifescience,medical and easily identify events that are likely to have these serious sequelae in order to take measures to reduce their impact. Objective tools to identify critical incidents which are likely to result in emotional difficulties might also reduce the stigma that EMT/paramedics experience when reporting such incidents, thus facilitating timely support. The first goal of this investigation was to develop an inventory of Inhibitors,research,lifescience,medical critical incident characteristics which are significantly associated with emotional distress at the time of an index critical incident and test the relationship of these characteristics with potential later sequelae, including slower recovery from symptoms of acute stress, and emotional symptoms occurring long after Inhibitors,research,lifescience,medical the incident. The second goal

was to make this inventory as brief and useful as possible by eliminating items which did not add substantially to the strength of the associations which were found. We chose to study both recovery from acute stress symptoms soon after a critical incident CYTH4 as well as occurrence of later emotional symptoms, because a chain of events may follow a critical incident. First, events which are appraised to be a greater threat than one has the resources to handle effectively elicit distress through an iterative process of appraisal, response and reappraisal [9]. Immediate (peritraumatic) distress may lead to the Acute Stress Reaction [10], which commonly includes physical arousal, distressing emotions, irritability, impaired sleep and social withdrawal, and usually returns to normal within hours or at most a few days.

In clinical practice it is still useful to follow a categorical approach at the first stage (diagnostic utility), but bearing in mind that bipolar depressions and nonbipolar depressions have a fluctuating course and also have mixed episodes of selleckchem depression and superimposed manic/hypomanic symptoms. The impact on treatment of these findings may be important for bipolar disorders and depressive disorders. If, when, and how long to use antidepressants and moodstabilizing agents in Inhibitors,research,lifescience,medical the light of the spectrum concept of mood disorders have to be defined, setting the stage for a new series of studies. Notes I wish

to thank Professor Jules Angst for his support and for his suggestions.
Decades of basic and clinical neuroscience research have greatly improved our understanding of the neurobiology of depression. Clinical studies have helped establish which treatments Inhibitors,research,lifescience,medical are effective, and have led to evidence-based treatment algorithms that can be readily applied to the “real-world” situation.1 Basic research has yielded insights into the genetic, molecular, cellular, and neuroanatomical bases of depression. Based on these findings, there is a growing acceptance of depression, Inhibitors,research,lifescience,medical and other mood disorders, as diseases of the brain rather

than purely aberrations of “mind.” Despite these advances, depression remains a common and inadequately treated illness, with few strategies for prevention or cure. The lifetime prevalence of depression approaches 17% in the United States,2 and depression is recognized Inhibitors,research,lifescience,medical to be one of the leading causes of disability worldwide.3,4 Available treatments for depression – including pharmacotherapy, evidence-based psychotherapy, and electroconvulsive therapy (ECT) – are Inhibitors,research,lifescience,medical effective in reducing symptoms in the majority of patients with an acute depressive episode, and the combination of these treatments may be more efficacious than individual treatments alone.5 However,

up to 40% of patients continue to have clinically significant symptoms despite optimized treatment,6 and up to 20% of patients may show little to no response to the most aggressive management (including the use of ECT).7-9 Even for patients ALOX15 who do respond to treatment, the illness tends to be highly recurrent, with up to 80% of patients experiencing at least one subsequent episode.10 Psychotherapy and/or maintenance antidepressant medications may substantially decrease the risk of relapse but do not eliminate it.11 In the face of these clear challenges, the continued neurobiological investigation of depression offers reason for optimism. Based on a solid foundation, basic and clinical neuroscience research is progressing rapidly, with many exciting developments on the horizon. Importantly, as the pathophysiology of depression becomes better understood, a number of novel treatment targets are being identified.

A free-breathing CT scan with 4-D respiratory correlation was also obtained to characterize target motion during quiet respiration. If target motion was >5 mm, respiratory gating using the Varian Respiratory Management System™ (Stanford), Cyberknife™ respiratory tracking (Stanford), or the Elekta Active Breathing Coordinator System™ (Hopkins) was utilized during treatment delivery. When available (12 of 18 patients), FDG-PET/CT

scans were fused with simulation scans. SBRT treatment plans were developed using Eclipse™ (Varian, Palo Alto, CA), Multi-Plan™ (Accuray, Sunnyvale, CA), or Pinnacle™ (Philips, Amsterdam, Netherlands). The gross tumor volume (GTV) was contoured Inhibitors,research,lifescience,medical by a radiation oncologist using the simulation scan. An internal target Inhibitors,research,lifescience,medical volume (ITV) was then defined after review of diagnostic imaging, respiratory-correlated

4D-CT, pancreas-protocol CT, and FDG-PET/CT scans. Final planning target volume (PTV) was obtained by an additional 1-3 mm uniform margin expansion of the ITV. The dose was prescribed to the isodose line that completely surrounded the PTV and 6-12 co-planar fields were used to generate the plan Inhibitors,research,lifescience,medical for non-Cyberknife™ treatments. Dose constraints for organs at risk were employed as follows: duodenum—V15Gy<9 cc, V20Gy<3 cc, V33Gy<1 cc; liver—D50%<12 Gy; stomach—D50%<12 Gy, V33Gy<1 cc; spinal cord—V8Gy<1 cc. Institutional standards for patient-specific dosimetric quality assurance were applied. SBRT delivery For non-Cyberknife™-based treatment (N=11), initial patient position was based on cone-beam CT with alignment to spine. Volumetric kV-imaging was then used to align biliary Inhibitors,research,lifescience,medical stent

and/or fiducials to the digitally-reconstructed radiograph. All fiducials were placed specifically for SBRT image guidance using an endoscopic approach (N=11 patients); complications of ERK inhibitor fiducial placement were observed in only one patient who experienced Inhibitors,research,lifescience,medical laryngospasm and had to return for repeat endoscopy the following day. Common bile duct stents Casein kinase 1 were placed endoscopically for relief of symptomatic biliary obstruction and not for purposes of SBRT image guidance, but if a stent was present, then fiducial placement was deemed unnecessary (N=4 patients). If a stent or fiducials were not present, patients were aligned to spine only (N=3). In patients who had previously undergone intra-tumoral fiducial placement, orthogonal kV/MV or kV/kV projection imaging was used to verify fiducial location before first treatment beam delivery and, if indicated, a secondary shift was performed. Active monitoring of treatment delivery accuracy was accomplished using kV and MV projection imaging. For CyberKnife™-based treatment (N=7; fiducials required), initial orthogonal kV/MV or kV/kV projection images were obtained to confirm fiducial location.

Among his seminal contributions to setting research paradigms in memory, he introduced

what would later be called “nonsense syllables”; today they are often termed consonant-vowelconsonant (CVC) trigrams. This methodology helped identify language-free learning characteristics (although it was later found that people do assign meaning to nonsense syllables). The work carried out in the tradition of Ebbinghaus (see 7) has helped shape our understanding of memory, especially more complex verbal and associative memory. For example, it has established the distinction between recognition and recall8 indices of memory, the former relating to the ability to judge whether Inhibitors,research,lifescience,medical the present Inhibitors,research,lifescience,medical stimulus (or experience) is “old” or “new” and the latter to the ability to recount the details of the stimulus. They investigated the veracity and distortions of memory traces and uncovered interference effects such as retroactive and proactive inhibition of memory associated with interfering events. Dimensions of memory The study of

memory has been characterized by evolving conceptions and methodologies in which competing distinctions have been Inhibitors,research,lifescience,medical emphasized over the years. The initial emphasis has been on associative learning and memory and the competing and, eventually, complementary paradigms of classical and operant conditioning have yielded information on the conditions and time course of the ability of organisms to learn new associations and retrieve acquired information. These initial efforts were developed without much attention to the neurological

or neuropsychological literature Inhibitors,research,lifescience,medical on memory. The young and ambitious science of behavior was firmly convinced that behavioral science could be erected without reference to its physical organ, the brain. Physiological measures were obtained as proxies for arousal, but theories did not consider ABT-888 mouse neuroscience evidence as being of much relevance Inhibitors,research,lifescience,medical to the theoretical articulation of memory. This situation has changed with advances in clinical and basic neuroscience. Clinical neuroscience has presented a series of highly informative cases and increased sophistication in documenting clinical-pathological correlations in routine cases. For example, the case of HM, who underwent bi-hippocampal Adenosine dissection and lost the ability to learn new information while retaining memories acquired prior to surgery, brought into sharp focus the role of the hippocampus in new learning.9, 10 Studies of patient populations with memory deficits related to seizure disorders, dementing disorders, and substance-use disorders have further identified distinct networks related to aspects of memory. At the same time, the advent of neuroimaging has opened up new avenues for probing memory processes in healthy and clinical populations.

The same is true for multifocal bilobar disease in which resection would leave a diminutive liver remnant insufficient for regeneration and normal hepatic function. Optimal preoperative imaging should readily identify small lesions and provide clear views of the hepatic artery, portal vein and hepatic veins avoiding an unnecessary laparotomy and aborted resection. While high quality preoperative imaging can help determine resectability, it is equally important in resection planning. Inhibitors,research,lifescience,medical With the exception of planned two-stage hepatic resections, the goal of metastasectomy is usually removal of all

metastatic lesions while preserving as much unaffected tissue as possible; maintaining segmental arterial blood supply as well as venous and biliary drainage is necessary to achieve this goal. This is rarely an issue for peripherally located lesions, which can typically be removed by wedge resection with little Inhibitors,research,lifescience,medical risk to major vessels or bile ducts. However, lesions located deep in the

liver parenchyma close to the hilum or hepatic veins require careful attention and planning. For example, a small lesion Inhibitors,research,lifescience,medical located close to the origin of the middle hepatic vein may require sacrificing that vessel. Failure to subsequently remove the segments of liver that drain through this vessel may result in significant Inhibitors,research,lifescience,medical hepatic congestion and necrosis. This often means performing an extended hepatectomy removing up to 80% of the hepatic parenchyma. If this lesion is not identified preoperatively on appropriate contrast-enhanced imaging and a larger resection is not anticipated, the patient may be left with inadequate liver

reserve. When recognized preoperatively, the portal vein supplying the planned resected lobe can be embolized prior to operation, allowing hypertrophy of the contralateral liver, thereby increasing remnant liver volume and reducing the risk of postoperative liver failure. Identifying lesions within the liver parenchyma can be Inhibitors,research,lifescience,medical difficult when extensive hepatic fibrosis or steatosis is present. This is often Dichloromethane dehalogenase the case is patients who have received preoperative chemotherapy, particularly oxaliplatin- and irinotecan-based regimens (6). Sinusoidal congestion and fatty replacement can lead to unpredictable alterations in the appearance of the liver resulting in false positive and negative studies. Radiologists reviewing images should be familiar with the extent of pre-imaging chemotherapy to better guide their study evaluation. Often more than one modality is required to garner the necessary preoperative information. For example, while CT is most commonly used for routine Cytoskeletal Signaling inhibitor cross-sectional imaging, MRI may be better for identifying occult liver lesions and their proximity to major vessels, and a PET scan better for ruling out extra-hepatic disease.

When PEG was conjugated to G5 and G6

PAMAM dendrimers (PEG-PAMAM) at three different molar ratios of 4%, 8%, and 15% (PEG to surface amine per PAMAM dendrimer molecule) [54], in vitro and in vivo cytotoxicities were reduced significantly. Also, hemolysis was reduced, especially at higher PEG molar ratios. Among all of the PEG-PAMAM dendrimers, 8% PEG-conjugated G5 and G6 dendrimers (G5-8% PEG, G6-8% PEG) were the most efficient in delivering genes to muscle Selleck AUY-922 following direct administration to neonatal mouse quadriceps (Figure5(c)). Consistent with the in vivo results, these two 8% PEG-conjugated PAMAM dendrimers could also mediate the highest in vitro transfection in 293A cells. Therefore, G5-8% PEG and G6-8% PEG possess a great Inhibitors,research,lifescience,medical potential for gene delivery and could conceivably be adapted to condense nucleic acids and be loaded atop

echogenic PLGA NP for US-mediated enhancements in intramuscular gene delivery. Other preparations successful in intramuscular gene delivery have been described, of interest since they enhance US-mediated gene delivery. Inhibitors,research,lifescience,medical These include efficient gene transfer in muscle to deliver basic fibroblast growth factor (bFGF) angiogenic gene therapy in limb Inhibitors,research,lifescience,medical ischemia. Bubble liposomes (DSPE-PEG2000-OMe with perfluoropropane) were used to transfect muscle in the presence of US [55]. In this example, bFGF was delivered and capillary vessels were enhanced and blood flow improved in the bFGF + MB + US-treated groups compared to other treatment groups (non-treated, bFGF alone, or bFGF + US). Skeletal muscle is a target of interest for gene delivery since it can mediate gene therapy of both muscle (e.g., Duchenne Muscular dystrophy) and nonmuscle disorders (e.g., cancer, ischemia, or arthritis). Its usefulness is due Inhibitors,research,lifescience,medical mainly Inhibitors,research,lifescience,medical to the long-term gene expression profile following gene transfer, which makes it an excellent target tissue for the high-level production of therapeutic proteins such as cytoskeletal proteins, trophic factors, hormones, or antitumor cytokines. Refining the conditions for sonoporation as well as the optimal formulation for achieving high-level

transgene expression in skeletal muscle will continue to be an important focus of gene therapy why delivery efforts for treating tumors, and in particular the delivery of antitumor cytokines. 3.1.4. MB Can Enhance NP Gene Delivery by Sonoporation in Muscle Tissue An interesting concept to aid NP gene delivery by sonoporation has employed combination with microbubbles in vivo. In one example, the hypothesis was tested that combination of a low concentration of MB could help reduce any US bioeffects and allow similar levels of transfection to occur when using PLGA NP at a lower US intensity and with a shorter duration in time. One interesting study examined the potential of improving siRNA delivery of retinal cells (RPE-J) in the presence of PLGA NP and a small amount of SonoVue MB [56].

The total amount of SWS is often decreased in depression, compared with normal controls.11 This reduction may be related to decreased regional cerebral blood flow seen in the orbitofrontal and anterior cingulate cortex during slow-wave sleep (SWS) in imaging studies,12 and it may be a consequence of the abnormalities in this area described in depression.13 In addition, reduction in SWS can reflect fragmented sleep in general, such as is seen in depression. Another anomaly seen in depressed patients is that the normal pattern of SWA decreasing from the first to the last NREM episode is disrupted, with less of a decrease in SWA occurring

from the first to the Sirolimus second episode in depressed patients14,15 Inhibitors,research,lifescience,medical (Figure 2). This is sometimes expressed as a lower delta sleep ratio (DSR) that is the quotient of SWA in the first to the second non-RRM period of sleep. Figure 2. Evolution of slow-wave activity over the night in a normal subject (upper) and a depressed patient (lower). In the normal subject the amount of slow-wave Inhibitors,research,lifescience,medical activity is high in the first nonREM period, then diminishes over the night. In the depressed patient, … Some of these sleep

Inhibitors,research,lifescience,medical architecture abnormalities are present during full clinical remission, and also appear to be associated with an increased risk for relapse.16-18 High REM density and reduced SWS in the first cycle were also present in first-degree relatives of depressed patients in the Munich Vulnerability Study on Affective Disorders, measured on two occasions 4 years apart,19 and in a more recent study, REM density predicted those who had subsequently developed

Inhibitors,research,lifescience,medical a major depressive episode.20 Mechanisms of sleep regulation and disturbances in depression Research over the past 25 years has revealed that the sleep-wake cycle is regulated Inhibitors,research,lifescience,medical by two separate but interacting processes,21 the circadian (C) process and the homeostatic (S), or recovery process. The C process is that which regulates the daily rhythms of the body and brain. Circadian (24-h) patterns of activity arc found in many organs and cells, and the main circadian pacemaker is found in a group of cells in the suprachiasmatic nucleus (SCN) of the hypothalamus. These cells provide an oscillatory pattern of activity which drives rhythms such as sleep-wake activity, hormone release, liver function, etc. This drive from the SCN is innate, self-sustaining, and independent of tiredness or amount of sleep. It is affected markedly by light next and to some extent by temperature. Bright light in the evening will delay the clock, and bright light in the morning is necessary to synchronize the clock to a 24-hour rhythm; in constant light or darkness the cycle length is about 24.3 h. All animals have such a clock, and the period and timing appear to be dependent on particular genes, which are similar in fruit flies and mammals. The drive to sleep from the circadian clock in normal sleepers starts to increase slowly at about 11 pm and gradually reaches a peak at about 4 am.

Interestingly, this

age-related difference in connectivity was not noted in the left hemisphere. This may suggest that the disruption in the default network by age might be more of a unilateral process than a bilateral one. Some task-based fMRI studies have already reported hemispheric asymmetry alteration of brain activity by age during the task performance (Cabeza 2002), and resting-state cerebral blood flow (Lu et al. 2011). However, to the best of our knowledge it has not been reported for DMN using resting-state BOLD fMRI data. We also compared our results with those obtained using the prevailing method in Inhibitors,research,lifescience,medical SMP8, which involves the typical spatial normalization by coregistering to MNI152 template and utilizing a set of predefined Inhibitors,research,lifescience,medical regional mask as the ROI across all the subjects in the study. However, utilization of data-driven atlases has gained popularity in recent years. They generate group-specific templates, and then a single standard space is derived from

those templates. Spatial normalization in this case is done in two steps, first Inhibitors,research,lifescience,medical nonlinear registration to group-specific template and then to the standard space template. This can certainly improve the accuracy of the nonlinear registration. However, utilization of highly accurate nonlinear registration for spatial normalization is hampered by overfitting problem. That is why most of the existing software packages (SPM, analysis of functional neuroimages, FSL, etc.) use a mild or moderate level of nonlinear registration in their spatial normalization. In either case, comparing the effectiveness of our approach to normalization with different atlas (data-driven or standard) is beyond the scope of this study, as our native space method totally eliminates the need for spatial Inhibitors,research,lifescience,medical normalization. The standard method produced three significant findings that did not survive Bonferroni correction and did not agree with any of the findings obtained with the new native space method. Only the change Inhibitors,research,lifescience,medical click here between one region pair (Hi, MOF) was found to be marginally

significant in the same hemisphere (left) in the native space analysis. Figure 6 also shows that spatial smoothing reduces the overall CYTH4 mean of the pair-wise correlations between the DMN nodes. The fact that we did not detect any significant changes after Bonferroni correction in elders’ DMN functional connectivity using SPM8 should not be surprising as many existing studies of age-related change in DMN have also failed to detect this difference (Bluhm et al. 2008; Beason-Held et al. 2009; Koch et al. 2010). Erroneous spatial normalization accompanied by strong spatial smoothing can simply cause a blending effect across regions which can deteriorate the contrast of the interregional functional connectivity between two groups. There are growing numbers of studies that consider the decline in functional connectivity in DMN as biomarker/hallmark of age-related cognitive decline.

Recent work has also implicated a similar range of cognitive deficits in other disorders that include psychosis. Even when euthymic, patients with bipolar disorder show cognitive impairments relative to healthy controls with medium to large effect sizes, especially within EF.29 As in schizophrenia, their first-degree relatives also have impairments in EF, albeit with small to medium effect sizes.29 Similarly, cognitive impairments in bipolar disorder correlate with poor functional capacity.30 More

Inhibitors,research,lifescience,medical broadly within the category of affective disorders, patients with Major Depressive Disorder (MDD) who have psychotic symptoms are also cognitively impaired to a similar degree to bipolar patients.31 Neuroimaging findings Consistent

with the neuropsychological literature, Inhibitors,research,lifescience,medical imaging studies of schizophrenia have used a variety of tasks that probe elements of EF with fMRI or positron emission tomography (PET) imaging. A meta-analysis that included all of these studies found that across all of the EF domains Inhibitors,research,lifescience,medical tested, patients consistently hypoactivated a set of largely lateral and medial see more prefrontal regions.32 Specifically, patients hypoactivated the DLPFC, ventrolateral PFC (VLPFC), dACC, and thalamus (in the region of the mediodorsal nucleus). This is consistent with the failure to engage normal cognitive control circuitry in the prefrontal cortex. Interestingly, greater activation was found in patients in a more posterior region of the dACC, along with a portion of the VLPFC, which may reflect network inefficiency or efforts to compensate Inhibitors,research,lifescience,medical for impaired activation of prefrontal cognitive control regions. In part, however, whether hypoactivation or hyperactivation is observed reflects the difficulty Inhibitors,research,lifescience,medical of the task. DLPFC activity in healthy subjects, for example, decreases from its peak as working memory is stressed beyond its maximal capacity.33 In line with the interpretation that the DLPFC of schizophrenic patients operates less efficiently than that of controls, patients hyperactivate

this region as they strain to keep up at low working memory loads that control subjects can easily handle, and almost hypoactivate this region at higher working memory loads that exceed patients’ working memorycapacity, but not that of controls.34 The network formulation of EF circuitry outlined above argues that cognitive impairments may arise because of failure to activate prefrontal cognitive control networks, failure to deactivate the default mode network, or abnormalities in the interaction between prefrontal cognitive control networks and the default mode network. In line with this prediction, patients with schizophrenia also display a failure to suppress activity in the default mode network with cognitively engaging tasks.

However, in a short period of time, an extensive body of research has accumulated. Here we will review the evidence for abnormalities of the hippocampal formation in schizophrenia. Hippocampal structure Many studies have found a subtle (about 5%) hippocampal and parahippocampal volume reduction in schizophrenia.51,165-168 Hippocampal volume reduction does not correlate with the duration of illness or correspond to schizophrenia subtypes such as deficit and nondeficit syndrome.37,169-171 In addition to changes in volume, changes in hippocampal Inhibitors,research,lifescience,medical shape have recently been reported.172 Furthermore, deficits of hippocampal structure (volume, N-acetylaspartate

levels) are also found in healthy-, firstdegree relatives of schizophrenic patients.173-175 Most studies have found no change in the number of hippocampal pyramidal neurons176-179

but nonpyramidal cells in the hippocampus (especially in CA2 subregion) seem to be reduced by 40 %.180 Studies of the orientation and position of pyramidal cells within the cornu Inhibitors,research,lifescience,medical ammonis subfields and of entorhinal cortex layer 2 cells are inconclusive.181-185 There is Inhibitors,research,lifescience,medical evidence that the intrinsic hippocampal fiber systems and the reciprocal connections of the hippocampal formation are perturbed, leading to a loss of neuropil and an overall loss of white matter.177,186-190 Synaptic Inhibitors,research,lifescience,medical organization is changed, possibly indicating altered plasticity of the hippocampus in schizophrenia.191-195 In addition to these postmortem studies, magnetic resonance spectroscopy studies

have provided evidence for abnormalities of membrane phospholipids and high-energy phosphate metabolism in the temporal lobe.76,196-200 Neurotransmitter systems Glutamate receptors of the kainic acid/amino-3-hydroxy5-methyl-4-isoxazole propionic acid (KA/AMPA) subtype, primarily the GluRl and GluR2 subunits, are decreased in the hippocampus in schizophrenia.201-205 GABA-uptake sites are reduced and GABAA receptors are upregulated, possibly due to the loss of GABAergic hippocampal Inhibitors,research,lifescience,medical interneurons.58,206-208 In addition, serotonergic 5-HT1A and 5-HT2 receptors are increased to and 5-HT-uptake sites are unchanged in the hippocampus in schizophrenia.209,210 Hippocampal function The metabolism and blood flow of the hippocampus are increased at baseline in schizophrenia.115,211,212 Furthermore, hippocampal and parahippocampal rCBF is increased during the experience of psychotic symptoms and correlates with positive symptoms (delusions, hallucinations).131,213 Recently, we have shown that hippocampal recruitment during the conscious recollection of semantically Dorsomorphin encoded words is impaired in schizophrenia.214 Schizophrenic patients displayed increased levels of hippocampal blood flow at rest and lacked the normal modulation that predicts recall accuracy in control subjects.