Concomitant progressive supranuclear palsy and chronic traumatic encephalopathy in a boxer.

We report the case of a 75-year-old ex-professional boxer who developed diplopia and eye movement abnormalities in his 60's followed by memory impairment, low mood and recurrent falls. Examination shortly before death revealed hypomimia, dysarthria, vertical supranuclear gaze palsy and impaired postural reflexes. Pathological examination demonstrated 4-repeat tau neuronal and glial lesions, including tufted astrocytes, consistent with a diagnosis of progressive supranuclear palsy. In addition, neurofibrillary tangles composed of mixed 3-repeat and 4-repeat tau and astrocytic tangles in a distribution highly suggestive of chronic traumatic encephalopathy were observed together with limbic TDP-43 pathology. Possible mechanisms for the co-occurrence of these two tau pathologies are discussed

Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

Clinicopathologic and molecular spectrum of RNASEH1-related mitochondrial disease.

OBJECTIVE: Pathologic ribonuclease H1 (RNase H1) causes aberrant mitochondrial DNA (mtDNA) segregation and is associated with multiple mtDNA deletions. We aimed to determine the prevalence of RNase H1 gene (RNASEH1) mutations among patients with mitochondrial disease and establish clinically meaningful genotype-phenotype correlations. METHODS: RNASEH1 was analyzed in patients with (1) multiple deletions/depletion of muscle mtDNA and (2) mendelian progressive external ophthalmoplegia (PEO) with neuropathologic evidence of mitochondrial dysfunction, but no detectable multiple deletions/depletion of muscle mtDNA. Clinicopathologic and molecular evaluation of the newly identified and previously reported patients harboring RNASEH1 mutations was subsequently undertaken. RESULTS: Pathogenic c.424G>A p.Val142Ile RNASEH1 mutations were detected in 3 pedigrees among the 74 probands screened. Given that all 3 families had Indian ancestry, RNASEH1 genetic analysis was undertaken in 50 additional Indian probands with variable clinical presentations associated with multiple mtDNA deletions, but no further RNASEH1 mutations were confirmed. RNASEH1-related mitochondrial disease was characterized by PEO (100%), cerebellar ataxia (57%), and dysphagia (50%). The ataxia neuropathy spectrum phenotype was observed in 1 patient. Although the c.424G>A p.Val142Ile mutation underpins all reported RNASEH1-related mitochondrial disease, haplotype analysis suggested an independent origin, rather than a founder event, for the variant in our families. CONCLUSIONS: In our cohort, RNASEH1 mutations represent the fourth most common cause of adult mendelian PEO associated with multiple mtDNA deletions, following mutations in POLG, RRM2B, and TWNK. RNASEH1 genetic analysis should also be considered in all patients with POLG-negative ataxia neuropathy spectrum. The pathophysiologic mechanisms by which the c.424G>A p.Val142Ile mutation impairs human RNase H1 warrant further investigation

Signal Detection on the Battlefield: Priming Self-Protection vs. Revenge-Mindedness Differentially Modulates the Detection of Enemies and Allies

Detecting signs that someone is a member of a hostile outgroup can depend on very subtle cues. How do ecology-relevant motivational states affect such detections? This research investigated the detection of briefly-presented enemy (versus friend) insignias after participants were primed to be self-protective or revenge-minded. Despite being told to ignore the objectively nondiagnostic cues of ethnicity (Arab vs. Western/European), gender, and facial expressions of the targets, both priming manipulations enhanced biases to see Arab males as enemies. They also reduced the ability to detect ingroup enemies, even when these faces displayed angry expressions. These motivations had very different effects on accuracy, however, with self-protection enhancing overall accuracy and revenge-mindedness reducing it. These methods demonstrate the importance of considering how signal detection tasks that occur in motivationally-charged environments depart from results obtained in conventionally motivationally-inert laboratory settings.National Institute of Mental Health (U.S.) (Grant MH64734)U.S. Army Research Institute for the Behavioral and Social Sciences (Grant W74V8H-05-K-0003)National Science Foundation (U.S.) (Grant BCS-0642873

Screening of depression in adolescents through the Internet: Sensitivity and specificity of two screening questionnaires.

.001). The scores on both instruments were significantly increased in all subjects with a mood disorder, whether current or lifetime, except for lifetime minor depression. In the ROC analyses, high areas under the curve were found for the MDI (0.89) and CESD (0.90). The best cut-off point for the MDI was 19 (sensitivity: 90.48; specificity: 71.53), and for the CES-D it was 22 (sensitivity: 90.48; specificity: 74.31). We conclude that the MDI and CES-D are reliable and valid instruments that can be used for this screening

Validation of a self-efficacy instrument and its relationship to performance of crisis resource management skills

Self-efficacy is thought to be important for resuscitation proficiency in that it influences the development of and access to the associated medical knowledge, procedural skills and crisis resource management (CRM) skills. Since performance assessment of CRM skills is challenging, self-efficacy is often used as a measure of competence in this area. While self-efficacy may influence performance, the true relationship between self-efficacy and performance in this setting has not been delineated. We developed an instrument to measure pediatric residents’ self-efficacy in CRM skills and assessed its content validity, internal structure, and relationship to other variables. After administering the instrument to 125 pediatric residents, critical care fellows and faculty, we performed an exploratory factor analysis within a confirmatory factor analysis as well as a known group comparison. The analyses specified four factors that we defined as: situation awareness, team management, environment management, and decision making. Pediatric residents reported lower self-efficacy than fellows and faculty in each factor. We also examined the correlation between self-efficacy and performance scores for a subset of 30 residents who led video recorded simulated resuscitations and had their performances rated by three observers. We found a significant, positive correlation between residents’ self-efficacy in situation awareness and environment management and their overall performance of CRM skills. Our findings suggest that in a specific context, self-efficacy as a form of self-assessment may be informative with regards to performance

Design strategies to improve patient motivation during robot-aided rehabilitation

BACKGROUND: Motivation is an important factor in rehabilitation and frequently used as a determinant of rehabilitation outcome. Several factors can influence patient motivation and so improve exercise adherence. This paper presents the design of two robot devices for use in the rehabilitation of upper limb movements, that can motivate patients during the execution of the assigned motor tasks by enhancing the gaming aspects of rehabilitation. In addition, a regular review of the obtained performance can reinforce in patients' minds the importance of exercising and encourage them to continue, so improving their motivation and consequently adherence to the program. In view of this, we also developed an evaluation metric that could characterize the rate of improvement and quantify the changes in the obtained performance. METHODS: Two groups (G1, n = 8 and G2, n = 12) of patients with chronic stroke were enrolled in a 3-week rehabilitation program including standard physical therapy (45 min. daily) plus treatment by means of robot devices (40 min., twice daily) respectively for wrist (G1) and elbow-shoulder movements (G2). Both groups were evaluated by means of standard clinical assessment scales and the new robot measured evaluation metric. Patients' motivation was assessed in 9/12 G2 patients by means of the Intrinsic Motivation Inventory (IMI) questionnaire. RESULTS: Both groups reduced their motor deficit and showed a significant improvement in clinical scales and the robot measured parameters. The IMI assessed in G2 patients showed high scores for interest, usefulness and importance subscales and low values for tension and pain subscales. CONCLUSION: Thanks to the design features of the two robot devices the therapist could easily adapt training to the individual by selecting different difficulty levels of the motor task tailored to each patient's disability. The gaming aspects incorporated in the two rehabilitation robots helped maintain patients' interest high during execution of the assigned tasks by providing feedback on performance. The evaluation metric gave a precise measure of patients' performance and thus provides a tool to help therapists promote patient motivation and hence adherence to the training program

Results of noninvasive ventilation in very old patients

International audienceABSTRACT: BACKGROUND: Noninvasive ventilation (NIV) is frequently used for the management of acute respiratory failure (ARF) in very old patients (>80 years), often in the context of a do-not-intubate order (DNI). We aimed to determine its efficacy and long-term outcome. METHODS: Prospective cohort of all patients admitted to the medical ICU of a tertiary hospital during a 2-year period and managed using NIV. Characteristics of patients, context of NIV, and treatment intensity were compared for very old and younger patients. Six-month survival and functional status were assessed in very old patients. RESULTS: During the study period, 1,019 patients needed ventilatory support and 376 (37%) received NIV. Among them, 163 (16%) very old patients received ventilatory support with 60% of them managed using NIV compared with 32% of younger patients (p < 0.0001). Very old patients received NIV more frequently with DNI than in younger patients (40% vs. 8%). Such cases were associated with high mortality for both very old and younger patients. Hospital mortality was higher in very old than in younger patients but did not differ when NIV was used for cardiogenic pulmonary edema or acute-on-chronic respiratory failure (20% vs. 15%) and in postextubation (15% vs. 17%) out of a context of DNI. Six-month mortality was 51% in very old patients, 67% for DNI patients, and 77% in case of NIV failure and endotracheal intubation. Of the 30 hospital survivors, 22 lived at home and 13 remained independent for activities of daily living. CONCLUSIONS: Very old patients managed using NIV have an overall satisfactory 6-month survival and functional status, except for endotracheal intubation after NIV failure