Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

International practice variation in perioperative laboratory testing in glioblastoma patients-a retrospective cohort study.

PURPOSE: Although standard-of-care has been defined for the treatment of glioblastoma patients, substantial practice variation exists in the day-to-day clinical management. This study aims to compare the use of laboratory tests in the perioperative care of glioblastoma patients between two tertiary academic centers-Brigham and Women's Hospital (BWH), Boston, USA, and University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. METHODS: All glioblastoma patients treated according to standard-of-care between 2005 and 2013 were included. We compared the number of blood drawings and laboratory tests performed during the 70-day perioperative period using a Poisson regression model, as well as the estimated laboratory costs per patient. Additionally, we compared the likelihood of an abnormal test result using a generalized linear mixed effects model. RESULTS: After correction for age, sex, IDH1 status, postoperative KPS score, length of stay, and survival status, the number of blood drawings and laboratory tests during the perioperative period were 3.7-fold (p < 0.001) and 4.7-fold (p < 0.001) higher, respectively, in BWH compared to UMCU patients. The estimated median laboratory costs per patient were 82 euros in UMCU and 256 euros in BWH. Furthermore, the likelihood of an abnormal test result was lower in BWH (odds ratio [OR] 0.75, p < 0.001), except when the prior test result was abnormal as well (OR 2.09, p < 0.001). CONCLUSIONS: Our results suggest a substantially lower clinical threshold for ordering laboratory tests in BWH compared to UMCU. Further investigating the clinical consequences of laboratory testing could identify over and underuse, decrease healthcare costs, and reduce unnecessary discomfort that patients are exposed to.

Which Domain of the PSY-5 Is Most Relevant to Substance Use?

Substance use has generally been related to lower levels of agreeableness and conscientiousness, but has evidenced relationships with other personality trait domains as well, including impulsivity. This study was conducted to determine which trait domain of personality is most related to substance use from the perspective of the Personality Psychopathology Five model (Harkness & McNulty, 1994 ). Archival data were used from 2 clinical settings: 1 outpatient community mental health center and 1 inpatient Veteran's Affairs hospital. The outpatient sample was mostly female (58.9%), White (78.7%), and had a mean age of 33.01 (SD = 10.26). The inpatient sample was entirely male, predominantly White (91.5%), and had a mean age of 48.03 (SD = 13.88). Correlations were conducted to identify the Minnesota Multiphasic Personality Inventory-2-Restructured Form Personality Psychopathology Five scales (Ben-Porath & Tellegen, 2008 ; Harkness et al., 2013 ) that were significantly related to variables measuring substance use. Subsequent regression analyses revealed that Disconstraint was the only significant predictor in the majority (89%) of analyses. In the event Disconstraint was not the only significant predictor, it continued to exhibit the largest unique predictive impact in the regression models. These results suggest that Disconstraint is the Personality Psychopathology-Five dimension most relevant to substance use.

Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa.

Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.

Viewing the MMPI-2-RF structure through the Personality Psychopathology Five (PSY-5) lens.

Ben-Porath and Tellegen (2008) recommend organizing MMPI-2-RF scale interpretive information around 3 broad topics, emotional/internalizing dysfunction, thought dysfunction, and externalizing/behavioral dysfunction, and 3 additional topics labeled somatic complaints, interpersonal functioning, and interests. That organization is based primarily on structural analyses of the Restructured Clinical (RC) scales. This study reviewed the MMPI-2-RF's scale structure when the Personality Psychopathology Five (PSY-5) scales are included. Principal axis factor analyses with oblique rotation were conducted on the Restructured Clinical, PSY-5, and Special Problem (SP) scales in 2 samples, by gender. One sample was an outpatient community health center, the other a large, metropolitan inpatient psychiatric facility. The 6-factor solution evidenced each of the PSY-5 constructs plus a general somatic concerns factor. Implications of this solution in comparison to the 3-factor organizing structure recommended by Ben-Porath and Tellegen are discussed.

The MMPI-2-RF Personality Psychopathology Five (PSY-5-RF) scales: development and validity research.

This article describes the development, internal psychometric, and external validation studies on scales designed to measure the Personality Psychopathology Five (PSY-5) from MMPI-2 Restructured Form (MMPI-2-RF) items. Diverse and comprehensive data sets, representing various clinical and nonclinical populations, were classified into development and validation research samples. Item selection, retention, and exclusion procedures are detailed. The final set of PSY-5-RF scales contain 104 items, with no item overlap between scales (same as the original MMPI-2 PSY-5 scales), and no item overlap with the Demoralization scale. Internal consistency estimates are comparable to the longer MMPI-2 PSY-5 scales. Appropriate convergent and discriminant validity findings utilizing various self-report, collateral rating, and record review data are reported and discussed. A particular emphasis is offered for the unique aspects of the PSY-5 model: psychoticism and disconstraint. The findings are connected to the broader PSY-5 literature and the recommended review of systems (Harkness, Reynolds, & Lilienfeld, this issue) presented in this series of articles.

Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictors of thoracic and lumbar spine injuries in patients with TBI: A nationwide analysis.

OBJECTIVE: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI. METHODS: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression. RESULTS: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures. CONCLUSIONS: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI.

Effect of a Mobile Health App on Adherence to Physical Health Treatment: Retrospective Analysis.

BACKGROUND: Adherence to prescribed medical interventions can predict the efficacy of the treatment. In physical health clinics, not adhering to prescribed therapy can take the form of not attending a scheduled clinic visit (no-show appointment) or prematurely terminating treatment against the advice of the provider (self-discharge). A variety of interventions, including mobile phone apps, have been introduced for patients to increase their adherence to attending scheduled clinic visits. Limited research has examined the impact of a mobile phone app among patients attending chiropractic and rehabilitation clinic visits. OBJECTIVE: This study aims to compare adherence to prescribed physical health treatment among patients attending a chiropractic and rehabilitation clinic who did and did not choose to adopt a phone-based app to complement their treatment. METHODS: The medical records of new patients who presented for care during 2019 and 2020 at 5 community-based chiropractic and rehabilitation clinics were reviewed for the number of kept and no-show appointments and to determine whether the patient was provider-discharged or self-discharged. During this 24-month study, 36.28% (1497/4126) of patients seen in the targeted clinics had downloaded the Kanvas app on their mobile phone, whereas the remaining patients chose not to download the app (usual care group). The gamification component of the Kanvas app provided the patient with a point every time they attended their visits, which could be redeemed as an incentive. RESULTS: During both 2019 and 2020, the Kanvas app group was provider-discharged at a greater rate than the usual care group. The Kanvas app group kept a similar number of appointments compared with the usual care group in 2019 but kept significantly more appointments than the usual care group in 2020. During 2019, both groups exhibited a similar number of no-show appointments; however, in 2020, the Kanvas app group demonstrated more no-show appointments than the usual care group. When collapsed across years and self-discharged, the Kanvas app group had a greater number of kept appointments compared with the usual care group. When provider-discharged, both groups exhibited a similar number of kept appointments. The Kanvas app group and the usual care group were similar in the number of no-show appointments when provider-discharged, and when self-discharged, the Kanvas app group had more no-show appointments compared with the usual care group. CONCLUSIONS: Patients who did or did not have access to the Kanvas app and were provider-discharged exhibited a similar number of kept appointments and no-show appointments. When patients were self-discharged and received the Kanvas app, they exhibited 3.2 more kept appointments and 0.94 more no-show appointments than the self-discharged usual care group.

Examining Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scale scores in a transgender and gender diverse sample.

Transgender and gender diverse (TGD) individuals are at increased risk of various forms of psychopathology. Little research has been conducted with broadband measures of psychopathology and TGD individuals. The present study sought to examine how TGD individuals scored on Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scales. This included MMPI-2-RF profiles from 85 TGD individuals; 37 were in mental health treatment and 48 of which were not. This study involved three sets of pairwise comparisons on MMPI-2-RF substantive scales via t-tests: (a) TGD individuals not in treatment versus the MMPI-2-RF normative sample, (v) TGD individuals not in treatment versus TGD individuals in treatment, and (c) TGD individuals in treatment versus a large outpatient clinical sample. Compared to the MMPI-2-RF normative sample, TGD individuals not in treatment scored significantly higher on 31 of the MMPI-2-RF substantive scales. Compared to those TGD individuals not in treatment, those in treatment had significantly higher scores on several MMPI-2-RF scales, primarily those of internalizing psychopathology. In the final comparison between TGD individuals in treatment and an outpatient clinical sample, the TGD individuals had some significantly higher and significantly lower scores on MMPI-2-RF substantive scales. Implications regarding minority stress and the current findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Are online student evaluations of faculty influenced by the timing of evaluations?

Student evaluations of faculty are important components of the medical curriculum and faculty development. To improve the effectiveness and timeliness of student evaluations of faculty in the physiology course, we investigated whether evaluations submitted during the course differed from those submitted after completion of the course. A secure web-based system was developed to collect student evaluations that included numerical rankings (1-5) of faculty performance and a section for comments. The grades that students received in the course were added to the data, which were sorted according to the time of submission of the evaluations and analyzed by Pearson's correlation and Student's t-test. Only 26% of students elected to submit evaluations before completion of the course, and the average faculty ratings of these evaluations were highly correlated [r(14) = 0.91] with the evaluations submitted after completion of the course. Faculty evaluations were also significantly correlated with the previous year [r(14) = 0.88]. Concurrent evaluators provided more comments that were statistically longer and subjectively scored as more "substantive." Students who submitted their evaluations during the course and who included comments had significantly higher final grades in the course. In conclusion, the numeric ratings that faculty received were not influenced by the timing of student evaluations. However, students who submitted early evaluations tended to be more engaged as evidenced by their more substantive comments and their better performance on exams. The consistency of faculty evaluations from year to year and concurrent versus at the end of the course suggest that faculty tend not to make significant adjustments to student evaluations.

Automating Clinical Chart Review: An Open-Source Natural Language Processing Pipeline Developed on Free-Text Radiology Reports From Patients With Glioblastoma.

PURPOSE: The aim of this study was to develop an open-source natural language processing (NLP) pipeline for text mining of medical information from clinical reports. We also aimed to provide insight into why certain variables or reports are more suitable for clinical text mining than others. MATERIALS AND METHODS: Various NLP models were developed to extract 15 radiologic characteristics from free-text radiology reports for patients with glioblastoma. Ten-fold cross-validation was used to optimize the hyperparameter settings and estimate model performance. We examined how model performance was associated with quantitative attributes of the radiologic characteristics and reports. RESULTS: In total, 562 unique brain magnetic resonance imaging reports were retrieved. NLP extracted 15 radiologic characteristics with high to excellent discrimination (area under the curve, 0.82 to 0.98) and accuracy (78.6% to 96.6%). Model performance was correlated with the inter-rater agreement of the manually provided labels (ρ = 0.904; P < .001) but not with the frequency distribution of the variables of interest (ρ = 0.179; P = .52). All variables labeled with a near perfect inter-rater agreement were classified with excellent performance (area under the curve > 0.95). Excellent performance could be achieved for variables with only 50 to 100 observations in the minority group and class imbalances up to a 9:1 ratio. Report-level classification accuracy was not associated with the number of words or the vocabulary size in the distinct text documents. CONCLUSION: This study provides an open-source NLP pipeline that allows for text mining of narratively written clinical reports. Small sample sizes and class imbalance should not be considered as absolute contraindications for text mining in clinical research. However, future studies should report measures of inter-rater agreement whenever ground truth is based on a consensus label and use this measure to identify clinical variables eligible for text mining.

An analysis of lecture video utilization in undergraduate medical education: associations with performance in the courses.

BACKGROUND: Increasing numbers of medical schools are providing videos of lectures to their students. This study sought to analyze utilization of lecture videos by medical students in their basic science courses and to determine if student utilization was associated with performance on exams. METHODS: Streaming videos of lectures (n = 149) to first year and second year medical students (n = 284) were made available through a password-protected server. Server logs were analyzed over a 10-week period for both classes. For each lecture, the logs recorded time and location from which students accessed the file. A survey was administered at the end of the courses to obtain additional information about student use of the videos. RESULTS: There was a wide disparity in the level of use of lecture videos by medical students with the majority of students accessing the lecture videos sparingly (60% of the students viewed less than 10% of the available videos. The anonymous student survey revealed that students tended to view the videos by themselves from home during weekends and prior to exams. Students who accessed lecture videos more frequently had significantly (p < 0.002) lower exam scores. CONCLUSION: We conclude that videos of lectures are used by relatively few medical students and that individual use of videos is associated with the degree to which students are having difficulty with the subject matter.

Apical sodium-dependent bile acid transporter inhibition with volixibat improves metabolic aspects and components of non-alcoholic steatohepatitis in Ldlr-/-.Leiden mice.

Interruption of bile acid recirculation through inhibition of the apical sodium-dependent bile acid transporter (ASBT) is a promising strategy to alleviate hepatic cholesterol accumulation in non-alcoholic steatohepatitis (NASH), and improve the metabolic aspects of the disease. Potential disease-attenuating effects of the ASBT inhibitor volixibat (5, 15, and 30 mg/kg) were investigated in high-fat diet (HFD)-fed Ldlr-/-.Leiden mice over 24 weeks. Plasma and fecal bile acid levels, plasma insulin, lipids, and liver enzymes were monitored. Final analyses included liver histology, intrahepatic lipids, mesenteric white adipose tissue mass, and liver gene profiling. Consistent with its mechanism of action, volixibat significantly increased the total amount of bile acid in feces. At the highest dose, volixibat significantly attenuated the HFD-induced increase in hepatocyte hypertrophy, hepatic triglyceride and cholesteryl ester levels, and mesenteric white adipose tissue deposition. Non-alcoholic fatty liver disease activity score (NAS) was significantly lower in volixibat-treated mice than in the HFD controls. Gene profiling showed that volixibat reversed the inhibitory effect of the HFD on metabolic master regulators, including peroxisome proliferator-activated receptor-γ coactivator-1ß, insulin receptor, and sterol regulatory element-binding transcription factor 2. Volixibat may have beneficial effects on physiological and metabolic aspects of NASH pathophysiology.

Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.

PURPOSE: Glioblastoma (GBM) is resistant to standard of care. Immune checkpoints inhibitors (such as anti-PD-1 mAbs) efficiently restore antitumor T-cell activity. We engineered a new oncolytic herpes simplex virus (oHSV) expressing a single-chain antibody against PD-1 (scFvPD-1) to evaluate its efficacy in mouse models of GBM. EXPERIMENTAL DESIGN: NG34scFvPD-1 expresses the human GADD34 gene transcriptionally controlled by the Nestin promoter to allow replication in GBM cells and a scFvPD-1 cDNA transcriptionally controlled by the CMV promoter. ELISA assays were performed to detect binding of scFvPD-1 to mouse and human PD-1. In vitro cytotoxicity and replication assays were performed to measure NG34scFvPD-1 oncolysis, and scFvPD-1 expression and secretion were determined. In vivo survival studies using orthotopic mouse GBM models were performed to evaluate the therapeutic potency of NG34scFvPD-1. RESULTS: NG34scFvPD-1-infected GBM cells express and secrete scFvPD-1 that binds mouse PD-1. The introduction of the scFvPD-1 sequence in the viral backbone does not alter the oncolytic properties of NG34scFvPD-1. In situ NG34scFvPD-1 treatment improved the survival with a tail of durable survivorship in 2 syngeneic immunocompetent mouse models of GBM. Mice that survived the first GBM challenge rejected the second challenge of GBM when implanted in the contralateral hemisphere. However, this was not true when athymic mice were employed as the recipients of the second challenge, consistent with the need for an intact immune system to obtain a memory response. CONCLUSIONS: NG34scFvPD-1 treatment induces a durable antitumor response in 2 preclinical mouse models of GBM with evidence for antitumor memory.

Swe1p responds to cytoskeletal perturbation, not bud size, in S. cerevisiae.

BACKGROUND: S. cerevisiae cells must grow to a critical size in G1 in order to pass start and enter the cell cycle. A recent study proposed that in addition to the mother size control in G1, the bud must grow to a critical bud size in G2 in order to enter mitosis. Insufficient bud size would cause G2 arrest enforced by the mitotic inhibitor Swe1p, explaining previous findings that some perturbations that block bud growth also trigger Swe1p-dependent cell-cycle arrest. RESULTS: We tested the critical-bud-size hypothesis. We found that halting bud growth by inactivation of the myosin Myo2p did not trigger Swe1p-dependent arrest in budded cells, even when the buds were very small. Moreover, Swe1p did not affect cell-cycle progression in unstressed cells, even when bud size was decreased by overriding G1 size control. Actin depolymerization did cause Swe1p-dependent arrest in small-budded but not large-budded cells, as previously reported. However, we found that the key determinant of cell-cycle arrest in those circumstances was not bud size, but rather the relative abundance of the Swe1p mitotic inhibitor and the mitosis-promoting cyclins. CONCLUSIONS: Swe1p does not respond to insufficient bud size. Instead, actin stress empowers Swe1p to promote arrest. The effectiveness of Swe1p in promoting that arrest declines as cells progress through the cell cycle.

Interpreting low Personality Psychopathology-Five Aggressiveness scores on the MMPI-2: graphical, robust, and resistant data analysis.

The Minnesota Mutiphasic Personality Inventory-2 (MMPI-2)-based Personality Psychopathology-Five (PSY-5) scales provide an overview of personality individual differences. Several textbooks and a test report offer instruction on interpreting MMPI-2 PSY-5 scores. On the basis of an earlier item response theory article (S. V. Rouse, M. S. Finger, & J. N. Butcher, 1999), low scores on the PSY-5 Aggressiveness (AGGR) scale are not currently interpreted. Traditional statistical methods are supplemented with graphical, robust, and resistant methods in the study of 188 outpatient men and 287 outpatient women. With locally weighted regression smoothing, the AGGR scale appeared to bear approximately linear relationships to scales formed from therapist ratings of patients. Pearson correlations tested by t test for significance showed correspondence with robust bootstrapped tests. Low-cut subsamples of men and women at or below the 33rd normative percentile showed that resistant correlations with robust tests showed moderate convergence with traditional methods. Results clearly suggested that low AGGR scores on the PSY-5 should be interpreted as suggesting low aggressiveness and passive and submissive features. Resistant and robust analyses suggest that gradations of aggressiveness, even within a low AGGR score group, can be interpreted.

The mechanics of corneal deformation and rupture for penetrating injury in the human eye.

Penetrating eye injuries are surgical emergencies with guarded visual prognosis. The purpose of the current study was to determine the force required to rupture the cornea with a penetrating object, and to study how this force is affected by the object geometry. Thirty-six human cadaveric eyes from donors of various ages were characterized for diameter, axial length, and pre-test intraocular pressure. In order to investigate the effects of specimen storage time on the tissue response, half of the specimens were tested within two weeks of donor expiration, and half of the specimens were stored at -4°C for 12-18 months. Indenters of three different diameters (1.0, 1.5, and 2.0mm) were lowered into the apex of the cornea until rupture. Resistance to displacement (stiffness), displacement at failure, and the force at failure were determined. Multi-variable regression analysis was used to determine associations of the input variables (indenter size, test speed, and tissue postmortem time) on the mechanics of the tissue response. Twenty-nine of the 36 specimens failed at the indenter location in the cornea, four failed at the limbus, and three failed in the sclera near sites of muscle attachment. The average force at failure caused by the 1.0mm, 1.5mm, and 2.0mm indenters increased from 30.5±5.5N to 40.5±8.3N to 58.2±14.5N, respectively (p<0.002). The force at failure was associated with the donor age (p<0.001), and globe diameter (p<0.041), but was not associated with pre-test intraocular pressure, tissue postmortem time, axial length, or speed of the indenter. This study has quantified the force-displacement and failure response of a large series of human cadaveric eyes subjected to penetrating indentation loads on the cornea. The results provide useful data for characterizing the relationship between corneal rupture and the geometry of a penetrating object.

Finite element analysis and experimental evaluation of penetrating injury through the cornea.

Penetration injuries of the eye are among the most frequent causes of permanent visual impairment resulting from trauma. The purpose of this study was to determine the peak strain at which rupture occurs in the cornea due to a penetrating object. Probes of varying diameters (1.0, 1.5, and 2.0mm) were pressed into the apex of the cornea of 36 human cadaveric eye specimens until perforation or rupture of the specimen at the cornea, limbus, or sclera occurred. An axisymmetric finite element model of the human globe was created to replicate the experimental set-up. The models were used to map the force-displacement response of the experiments and quantitatively determine a peak strain at which the eye ruptures. For the experiments, the average force at failure increased from the smallest to largest probe (p<0.002). The average forces at failure are as follows: 30.5±5.5N (1.0mm probe); 40.5±8.3N (1.5mm probe); 58.2±14.5N (2.0mm probe). The force-displacement responses of the finite element models of all three probe sizes bounded and tracked the experimental data. In all cases, the peak strain at failure in the cornea was located on the posterior surface of the cornea, directly adjacent to the corneal apex. This strain was in the range of 29% to 33% for all models analyzed. In addition to determining an objective failure strain of corneal tissue, the model developed in this study can provide quantitative information for understanding the risk of penetrating eye injuries.

Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT) in the chicken.

BACKGROUND: Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle. RESULTS: PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+), which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75-80%), CD8+ (20-25%), TCRalphabeta/Vbeta1+ (60%), and TCRgammadelta+ (15%). All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRalphabeta/Vbeta1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h) compared to the dark:light interphase (0700 h). CONCLUSION: The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light:dark cycle and that CD8+ and TCRgammadelta+ T-cells are preferentially recruited to the pineal follicles. Pineal microglia/macrophages were common and represent an important candidate for mediating these lymphocyte-pineal interactions via secretion of cytokines and chemokines.