Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions.

Background: Delirium following cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. Preoperative protein signatures may identify patients at increased risk for worse postoperative outcomes, including delirium. In this study, we aimed to identify plasma protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery, while also uncovering possible pathophysiological mechanisms. Methods: SOMAscan analysis of 1,305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (PREOP) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the ELLA multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology. Results: A total of 115 and 85 proteins from SOMAscan analyses were found altered in delirious patients at PREOP and POD2, respectively (p<0.05). Using four criteria including associations with surgery, delirium, and biological plausibility, 12 biomarker candidates (Tukey's fold change (|tFC|)>1.4, Benjamini-Hochberg (BH)-p<0.01) were selected for ELLA multiplex validation. Eight proteins were significantly altered at PREOP, and seven proteins at POD2 (p<0.05), in patients who developed postoperative delirium compared to non-delirious patients. Statistical analyses of model fit resulted in the selection of a combination of age, sex, and three proteins (angiopoietin-2 (ANGPT2); C-C motif chemokine 5 (CCL5); and metalloproteinase inhibitor 1 (TIMP1); AUC=0.829) as the best performing predictive model for delirium at PREOP. The delirium-associated proteins identified as biomarker candidates are involved with inflammation, glial dysfunction, vascularization, and hemostasis, highlighting the multifactorial pathophysiology of delirium. Conclusion: Our study proposes a model of postoperative delirium that includes a combination of older age, female sex, and altered levels of three proteins. Our results support the identification of patients at higher risk of developing postoperative delirium after cardiac surgery and provide insights on the underlying pathophysiology. ClinicalTrials.gov ( NCT02546765 ).

The Effect of Inner Engineering Online (IEO) Program on Reducing Stress for Information Technology Professionals: A Randomized Control Study.

In recent years, mindfulness-based interventions (MBIs) are rapidly growing in the workplace. Several meta-analyses conclude that overall MBIs have a moderate effect of alleviating deficit-based experiences, such as burnout and stress, but a small to no effect of promoting asset-based experiences, such as positive affect and well-being. While workplace MBIs vary greatly in their content, format, and duration, the dominant format is still face to face in a group setting, which limits scalability. Our study introduces an emerging workplace intervention called Inner Engineering Online (IEO) and evaluates its effect on reducing stress, burnout, depression, and anxiety and increasing mindfulness and joy. Drawing on the classical yogic science, IEO is a comprehensive web-based multicomponent intervention that utilizes dialectic discourse, meditation, and yogic practices designed to improve physical, mental, and emotional health. Utilizing a randomized active control cross-over experimental design with a sample of 71 employees of an Information Technology company, we tested our hypothesis that IEO training and regular daily yogic practice are likely to lower the stress levels, prevent burnout, and alleviate anxiety and depression, while at the same time promotes positive affect for employees. The results show that IEO program significantly reduces stress only among those who adhere to recommended daily yogic practices. The study is limited by its small sample size. Future research using a large sample is recommended to reexamine the effect of IEO training on occupational health. This trial is registered with NCT04126564.

Perceived stress, resilience, well-being, and COVID 19 response in Isha yoga practitioners compared to matched controls: A research protocol.

OBJECTIVES: The COVID-19 pandemic has been a significant stressor worldwide and reports of psychological distress, depression, sedentary lifestyles, and overall decreased wellbeing are increasing. Yoga practices have been found to improve mental and physical health. The purpose of this randomized controlled trial is to compare Isha yoga practitioners to controls on perceived stress, resilience, wellbeing, and protection and recovery from COVID-19. Trial Design. In this prospective randomized control trial, the effects of yoga practices are being compared between seasoned yoga practitioners with two controls who are age (±3 years), gender matched, and living in the same neighborhood. METHODS: Participants will be asked to complete a series of web-based surveys at baseline, six weeks, and 12 weeks. These surveys include validated scales and objective questions on COVID-19 infection and medical history. The validated questionnaires assess stress, mood states, resilience, and overall wellbeing. Questionnaires, weekly activity diaries, and medical history, will be collected using REDCap. RESULTS: We hypothesize that routine yoga practice during the COVID-19 pandemic will reduce stress, enhance well-being, and provide protective effects against COVID-19. CONCLUSION: With the growing concern about the physical and mental impacts of COVID-19 and increased interest in alternative practices such as yogic practices, this study will contribute to the growing body of evidence about the safety and efficacy of yoga for emotional, mental, and physical health conditions.

Obliquity of the Stapes in Otosclerosis: A New Radiological Sign

Abstract Introduction Observing the obliquity of stapes by closely scrutinizing the HRCT temporal bone in otosclerosis revealed a reliable and consistent finding. This finding can add to the existing radiological criteria in diagnosis of otosclerosis. Objective The objective of this study is to establish the obliquity of stapes in otosclerosis by radiological measurements using HRCT temporal bone by comparing: (a) the distance between the horizontal (tympanic) segment of facial nerve and stapes head in otosclerotic ears (study group) with non-otosclerotic ears (control group); and (b) the angle subtended by stapes with promontory in the study and control groups. Methods This is a prospective study performed after the institutional Ethics Committee clearance (IEC 3/2013). Results An increased mean distance between the horizontal segment of facial nerve and stapes head in otosclerotic patients (i.e., 2.49mm +/ 0.24mm SD), when compared with the non-otosclerotic patients (i.e., 1.46mm +/ 0.16mm SD) is noted. There is a change in angle (i.e., 64.550 +/ 7.190 SD) subtended by the stapes toward the promontory in otosclerotic ears when compared with that of controls (i.e., 99.700 +/ 40 SD). We applied the Mann-Whitney U non-parametric test and considered p value of < 0.0001 highly significant. Conclusions Obliquity of stapes in otosclerosis referred to as a "Pisa" sign by the senior author has diagnostic value as a new radiological sign in imaging of otosclerosis. This obliquity explains the torsional effect of otosclerosis on the ossicular chain. The findings correlate with late complications and failures in stapes surgery.

Obliquity of the Stapes in Otosclerosis: A New Radiological Sign.

Introduction Observing the obliquity of stapes by closely scrutinizing the HRCT temporal bone in otosclerosis revealed a reliable and consistent finding. This finding can add to the existing radiological criteria in diagnosis of otosclerosis. Objective The objective of this study is to establish the obliquity of stapes in otosclerosis by radiological measurements using HRCT temporal bone by comparing: (a) the distance between the horizontal (tympanic) segment of facial nerve and stapes head in otosclerotic ears (study group) with non-otosclerotic ears (control group); and (b) the angle subtended by stapes with promontory in the study and control groups. Methods This is a prospective study performed after the institutional Ethics Committee clearance (IEC 3/2013). Results An increased mean distance between the horizontal segment of facial nerve and stapes head in otosclerotic patients (i.e., 2.49mm +/- 0.24mm SD), when compared with the non-otosclerotic patients (i.e., 1.46mm +/- 0.16mm SD) is noted. There is a change in angle (i.e., 64.550 +/- 7.190 SD) subtended by the stapes toward the promontory in otosclerotic ears when compared with that of controls (i.e., 99.700 +/- 40 SD). We applied the Mann-Whitney U non-parametric test and considered p value of < 0.0001 highly significant. Conclusions Obliquity of stapes in otosclerosis referred to as a "Pisa" sign by the senior author has diagnostic value as a new radiological sign in imaging of otosclerosis. This obliquity explains the torsional effect of otosclerosis on the ossicular chain. The findings correlate with late complications and failures in stapes surgery.

Scheduled prophylactic ondansetron administration did not improve its antiemetic efficacy after intracranial tumour resection surgery in children.

BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting after craniotomy may increase intracranial pressure and morbidity in children. This prospective, randomized, placebo-controlled and double-blinded study was designed to evaluate the antiemetic efficacy of prophylactic ondansetron after intracranial tumour resections in children. METHODS: Ninety children were divided into three groups and received saline (Group 1), ondansetron 150 microg kg-1 intravenously at dural closure (Group 2) or two doses of ondansetron 150 microg kg-1 intravenously, the second dose repeated after 6 h (Group 3). Episodes of nausea, emesis and side-effects were noted for 24 h postoperatively. RESULTS: Overall 24 h incidence of postoperative nausea and vomiting was not significantly different among the three groups (9 (37.5%) in Group 1 vs. 7 (27%) in Group 2 and 8 (32%) in Group 3, P = 0.73). No difference in rescue antiemetic treatment or postoperative nausea and vomiting at specific time intervals (0-6 and 6-24 h postoperative period) was seen among the three groups. No significant side-effects were noted in any of the three groups. CONCLUSIONS: Ondansetron, in this study of 90 children, was not very effective in preventing nausea and vomiting after neurosurgical operations.

Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect.

UNLABELLED: In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures. IMPLICATIONS: Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.

Dexamethasone is a cost-effective alternative to ondansetron in preventing PONV after paediatric strabismus repair.

This study evaluated the antiemetic efficacy, cost-effectiveness and clinical utility of prophylactic ondansetron and dexamethasone compared with placebo in the prevention of postoperative nausea and vomiting (PONV) in 135 children (2-15 yr, ASA I-II) undergoing strabismus repair. After induction with halothane and nitrous oxide in oxygen or i.v. thiopental, the children received i.v. dexamethasone 1 mg kg(-1) to a maximum of 25 mg, ondansetron 100 microg kg(-1) to a maximum of 4 mg or placebo (n=45). Episodes of PONV were recorded for the first 24 h after the operation. True outcome measures (parental satisfaction score, duration of stay in the postanaesthesia care unit and fast tracking time), therapeutic outcome measures (number needed to prevent (NNTP) PONV) and the cost to benefit a child with each drug were analysed. The incidence and severity of PONV in the first 24 h were significantly less in the dexamethasone and ondansetron groups than in the placebo group (P<0.05). The incidence (P=0.04) and severity (P=0.03) of PONV at the 6-24 h epoch were significantly less in the dexamethasone group than in the ondansetron group. Recovery time (P=0.07), fast tracking time (P=0.6), parental satisfaction scores (P=0.08) and NNTP PONV were comparable (NNTP=2) in both the ondansetron and the dexamethasone group. The cost to benefit a child with dexamethasone was approximately 22 times less than that of ondansetron.

Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery.

STUDY OBJECTIVE: To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary care referral and teaching hospital. PATIENTS: 46 ASA physical status I and II patients who underwent major upper abdominal procedures. INTERVENTIONS: Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively. MEASUREMENTS: A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups. RESULTS: Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups. CONCLUSIONS: The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.

Autoxidation of substituted phenols catalyzed by cobalt Schiff base complexes in supercritical carbon dioxide.

This first study of O(2) oxidation (autoxidation) of substituted phenols catalyzed by a dioxygen carrier in supercritical carbon dioxide (scCO(2)) provides additional insights into the established mechanism of reactions that have been much studied in conventional solvents. As has been long believed, the cobalt(II) dioxygen carriers of the class represented by [[N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II)], Co(salen), show both oxidase and oxygenase activities during oxygenation of substituted phenols in scCO(2). The catalytic autoxidation of 2,6-di-tert-butylphenol (DTBP) and 3,5-di-tert-butylphenol (35-DTBP) in scCO(2) was studied by analysis of products in batch reactions with carefully controlled variables, in the presence of a large excess of O(2), at 207 bar of total pressure and a reaction temperature of 70 degrees C. The oxidation of 35-DTBP yielded only traces of products under the same experimental conditions that converted DTBP totally to a mixture of the oxygenation product 2,6-di-tert-butyl-1,4-benzoquinone (DTBQ) and the related product of radical coupling 3,5,3',5'-tetra-tert-butyl-4,4'-diphenoquinone (TTDBQ). The effects on conversion of DTBP to products and on selectivity between the two products were studied for variations in temperature and the concentrations of catalyst, oxygen, and methylimidazole. Selectivity in favor of the O-transfer product DTBQ over the self-coupling of the phenoxy radical was observed upon changing the oxygen concentration. In contrast, selectivity remained unaffected over a wide range of temperatures and catalyst concentrations. The oxygen dependence of both the conversion and selectivity showed saturation effects identifying the dioxygen complex as the effective oxidant in both the initial radical formation step and the oxygenation of that radical. No direct reaction is observed between the electrophilic phenoxy radical and O(2).

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Pre-emptive analgesia with epidural morphine or morphine and bupivacaine.

Studies of preemptive analgesia in humans have shown conflicting results. The study design, patient population and the duration of assessment of postoperative pain are important in the evaluation of preemptive analgesia. We carried out a prospective, randomized, double-blind controlled study in 80 patients of physical status ASA 1-3 undergoing upper abdominal and thoracic surgery. Patients received two epidural injections, one 20 minutes before induction and the other at the end of surgery. Study solution was either morphine (50 micrograms/kg), with or without 0.1% bupivacaine in 10 ml of normal saline, or normal saline alone. The study groups (Pre M, Pre MB) were given either morphine or morphine-bupivacaine before induction and saline at the end of surgery. The control groups (Post M, Post MB) were given saline before induction and morphine or morphine-bupivacaine at the end of surgery. Postoperative pain was assessed with a Visual Analogue Scale (VAS) during coughing and deep breathing at six-hourly intervals for five days. Epidural morphine was given if the VAS exceeded 4. Pre MB compared to Post MB had a significantly increased interval between the analgesic top-ups (P < 0.01) and decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.001). Pre M and Post M were comparable. Pre MB compared to Pre M had significantly decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.0001). Epidural morphine plus bupivacaine is effective as a preemptive analgesic. Morphine plus bupivacaine has better efficacy than morphine given alone before the induction of anaesthesia.

Balancing selection on a floral polymorphism.

The common morning glory, Ipomoea purpurea, exhibits a flower color polymorphism at the W locus throughout the southeastern North America. The W locus controls whether flowers will be darkly pigmented (WW), lightly pigmented (Ww), or white with pigmented rays (ww). In this report, we describe results of a perturbation, or convergence, experiment using five plots designed to determine whether balancing selection operates on the W locus. The pattern of gene frequency changes obtained are indicative of balancing selection operating at the W locus, providing direct evidence that both the alleles are actively maintained by selection.

Tethered cord syndrome in children with anorectal malformations.

OBJECT: Anorectal malformations are known to be associated with neurological deficits, which may contribute to the disability suffered by patients with these malformations. This study was undertaken to determine the incidence and pattern of sacral abnormalities in children with anorectal malformations, the incidence and nature of the neurological deficits, and the incidence and nature of operable intraspinal abnormalities in patients with this condition. METHODS: Neurological evaluation was performed in 81 children with anorectal malformations. Plain x-ray films were obtained to identify the presence of sacral abnormalities. The patients with neurological deficits were evaluated for the presence of operable intraspinal anomalies, and when such anomalies were identified, correction of the same was undertaken. In 21% of these children radiographic evidence of sacral abnormalities was shown. Fifteen percent of patients harbored neurological deficits, and 10% harbored operable intraspinal anomalies. In addition, one patient had split notochord syndrome. Patients with operable intraspinal anomalies underwent surgical correction, with resultant neurological improvement. CONCLUSIONS: Bone abnormalities of the sacrum, neurological deficits, and operable intraspinal lesions are not uncommon in children with anorectal malformations. Because the neurological deficits can contribute to the disability suffered by these individuals, we recommend routine screening of patients with anorectal malformations and neurological deficits and/or sacral abnormalities for the early identification and treatment of potentially correctable intraspinal lesions.

Balanced interactions in ganglion-cell receptive fields.

Receptive fields of retinal ganglion cells in turtle have excitatory and inhibitory components that are balanced along the dimensions of wavelength, functional ON and OFF responses, and spatial assignments of center and surround. These components were analyzed by spectral light adaptations and by the glutamate agonist, 2-amino-4-phosphonobutyric acid (APB). Extracellular recordings to stationary and moving spots of light were used to map changes in receptive fields. ON spike counts minus OFF spike counts, derived from flashed stationary light spots, quantified functional shifts by calculating normalized mean response modulations. The data show that receptive fields are not static, but rather are dynamic arrangements which depend on linked, antagonistic balances among the three dimensions of wavelength, ON and OFF response functions, and center/surround areas.

Three-dimensional quantitative structure-activity relationship study of the cannabimimetic (aminoalkyl)indoles using comparative molecular field analysis.

The present study describes the implementation of comparative molecular field analysis (CoMFA) to develop two 3D-QSAR (quantitative structure-activity relationship) models (CoMFA models 1 and 2) of the cannabimimetic (aminoalkyl)indoles (AAIs) for CB1 cannabinoid receptor binding affinity, based on pKi values measured using radioligand binding assays that displace two different agonist ligands, [3H]CP-55940 and [3H]WIN-55212-2. Both models exhibited a strong correlation between the calculated steric-electrostatic fields and the observed biological activity for the respective training set compounds. In light of the basicity of the morpholine nitrogen in the AAIs, separate CoMFA models were built for the AAIs as unprotonated and protonated species. Comparison of the statistical parameters resulting from these CoMFA models failed to provide unequivocal evidence as to whether the AAIs are protonated or neutral as receptor-bound species. Although the training sets of CoMFA model 1 and CoMFA model 2 differed with respect to composition and to the choice of displacement radioligand in each biological assay, their CoMFA StDevCoeff contour plots reveal similarities in terms of identifying those regions around the AAIs that are important for CB1 cannabinoid receptor binding such as the sterically favored region around the C3 aroyl group and the sterically forbidden region around the indole ring. When the experimental pKi values for the training set compounds to displace the AAI radioligand [3H]WIN-55212-2 were plotted against the pKi values as predicted for the same compounds to displace the cannabinoid radioligand [3H]CP-55940, the correlation was moderately strong (r = 0.73). However, the degree of correlation may have been lowered by the structural differences in the compounds comprising the training sets for CoMFA model 1 and CoMFA model 2. Taken together, the results of this study suggest that the binding site region within the CB1 cannabinoid receptor can accommodate a wide range of structurally diverse cannabimimetic analogues including the AAIs.

Edge complexity and partial volume effects.

PURPOSE: The accuracy of MR brain image segmentation is limited by so-called partial volume effects. We hypothesized that "edge complexity" (i.e., tissue class interface border complexity) significantly influences the magnitude of such effects. METHOD: To investigate partial volume effects and provide a vehicle for validation of segmentation algorithm accuracy in brain MRI. We developed a computer simulation, the "gigabrain." The simulation is based on interpolated (supersampled) data from actual MR studies. The voxels are assigned to one of five compartments (gray matter, white matter, CSF, fat, or "background"), the compartment interfaces are "jittered" to add high frequency "signal" or "edge complexity," and the voxels are populated with appropriate values determined from human data, low pass filtered (based on the MR scanner's point spread function), and subsampled back to the sampling and voxel size of the original MR data set. RESULTS: In comparison studies with actual phantoms and human MR data, our simulation approach was able to produce images whose appearance and quantitative values were comparable with the actual data, but only when edge complexity was added to the original MR data. CONCLUSION: Edge complexity is a significant source of partial volume effects. MR simulations must include edge complexity to adequately test segmentation algorithms.

Pharmaceutical processing with supercritical carbon dioxide.

Replacement of traditional solvents with "environmentally benign" carbon dioxide is receiving increased attention in pharmaceutical processing. Among the reported applications, particle formation with dense carbon dioxide and the "clean" synthesis of drug compounds using carbon dioxide as a reaction medium hold immense potential for large-scale application in the pharmaceutical industry. This paper provides an overview of these rapidly emerging technologies along with examples of the wide variety of relatively contaminant-free pharmaceutical compounds that have been processed via these technologies on a laboratory scale. Challenges facing successful implementation in practice include demonstration of continuous production and harvesting of particles with desired and reproducible product characteristics. Mathematical models aimed at a better fundamental understanding of the underlying thermophysical phenomena are essential for rational design and scale-up of these technologies.

Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa.

Rett syndrome (RS), a neurodevelopmental disorder of unknown etiology occurring almost exclusively in females, is characterized by autistic-like behavior, motor dysfunction, loss of language skills, dementia, and microcephaly. This study is a follow-up and extension of a previously reported neuroimaging study of patients with RS. We replicated previously reported findings with a larger patient population, and the volumetric MRI analysis was extended to include an analysis of neuroanatomy of the posterior fossa. Twenty girls with RS were compared with individually age- and gender-matched normal controls. Patients with RS showed global reduction in gray- and white-matter volumes. The prefrontal, posterior-frontal, and anterior-temporal regions showed the largest bilateral decrease in gray-matter volume, whereas white-matter volume was uniformly reduced throughout the brain. We found confirmation for the preferential reduction in caudate nucleus volume. However, we observed no preferential reduction in midbrain volume despite a preferential reduction in the midsagittal area of this region. We also present an individual case comparison between monozygotic twins discordant for RS.

The role of visual attention in saccadic eye movements.

The relationship between saccadic eye movements and covert orienting or visual spatial attention was investigated in two experiments. In the first experiment, subjects were required to make a saccade to a specified location while also detecting a visual target presented just prior to the eye movement. Detection accuracy was highest when the location of the target coincided with the location of the saccade, suggesting that subjects use spatial attention in the programming and/or execution of saccadic eye movements. In the second experiment, subjects were explicitly directed to attend to a particular location and to make a saccade to the same location or to a different one. Superior target detection occurred at the saccade location regardless of attention instructions. This finding shows that subjects cannot move their eyes to one location and attend to a different one. The result of these experiments suggest that visuospatial attention is an important mechanism in generating voluntary saccadic eye movements.