Research has demonstrated that the extent to which an individual integrates a traumatic event into their identity (“trauma centrality”) positively correlates with posttraumatic stress disorder (PTSD) ...symptom severity. No research to date has examined trauma centrality in individuals exposed to combat stress. This study investigated trauma centrality using the abridged Centrality of Event Scale (Berntsen & Rubin, 2006) among Operation Enduring Freedom/Operation Iraqi Freedom combat veterans (n = 46). Multiple regression analyses demonstrated that trauma centrality predicted PTSD symptoms. Trauma centrality and PTSD symptoms remained significantly correlated when controlling for depression in subgroups of veterans with or without probable PTSD. This study replicates and extends findings that placing trauma at the center of one's identity is associated with PTSD symptomatology.
We propose a method of measuring people's sense of presence in computer-mediated communication (CMC) systems) based on linguistic features of their dialogues. We create variations in presence by ...asking participants to collaborate on physical tasks in four CMC conditions. We then correlate self-reported feelings of presence with the use of specific linguistic features. Regression analyses show that 30% of the variance in self-reported presence can be accounted for by a small number of task-independent linguistic features. Even better prediction can be obtained when self-reported coordination is added to the regression equation. We conclude that linguistic measures of presence have value for studies of CMC.
The aetiology and pathogenesis of non-genetic forms of frontotemporal dementia (FTD) is unknown and even with the genetic forms of FTD, pathogenesis remains elusive. Given the association between ...systemic inflammation and other neurodegenerative processes, links between autoimmunity and FTD need to be explored.
To describe the prevalence of systemic autoimmune disease in semantic variant primary progressive aphasia (svPPA), a clinical cohort, and in progranulin (PGRN) mutation carriers compared with neurologically healthy normal controls (NC) and Alzheimer's disease (AD) as dementia controls.
Case control.
Academic medical centres.
129 svPPA, 39 PGRN, 186 NC and 158 AD patients underwent chart review for autoimmune conditions. A large subset of svPPA, PGRN and NC cohorts underwent serum analysis for tumour necrosis factor α (TNF-α) levels.
χ(2) Comparison of autoimmune prevalence and follow-up logistic regression.
There was a significantly increased risk of autoimmune disorders clustered around inflammatory arthritides, cutaneous disorders and gastrointestinal conditions in the svPPA and PGRN cohorts. Elevated TNF-α levels were observed in svPPA and PGRN compared with NC.
svPPA and PGRN are associated with increased prevalence of specific and related autoimmune diseases compared with NC and AD. These findings suggest a unique pattern of systemic inflammation in svPPA and PGRN and open new research avenues for understanding and treating disorders associated with underlying transactive response DNA-binding protein 43 aggregation.
Objective
Progressive supranuclear palsy (PSP) has been conceptualized as a large‐scale network disruption, but the specific network targeted has not been fully characterized. We sought to delineate ...the affected network in patients with clinical PSP.
Methods
Using task‐free functional magnetic resonance imaging, we mapped intrinsic connectivity to the dorsal midbrain tegmentum (dMT), a region that shows focal atrophy in PSP. Two healthy control groups (1 young, 1 older) were used to define and replicate the normal connectivity pattern, and patients with PSP were compared to an independent matched healthy control group on measures of network connectivity.
Results
Healthy young and older subjects showed a convergent pattern of connectivity to the dMT, including brainstem, cerebellar, diencephalic, basal ganglia, and cortical regions involved in skeletomotor, oculomotor, and executive control. Patients with PSP showed significant connectivity disruptions within this network, particularly within corticosubcortical and cortico‐brainstem interactions. Patients with more severe functional impairment showed lower mean dMT network connectivity scores.
Interpretation
This study defines a PSP‐related intrinsic connectivity network in the healthy brain and demonstrates the sensitivity of network‐based imaging methods to PSP‐related physiological and clinical changes. Ann Neurol 2013;73:603–616
Frederick Sanger’s early work on protein sequencing through the use of colorimetric labeling combined with liquid chromatography involves an important nucleophilic aromatic substitution (SNAr) ...reaction in which the N-terminus of a protein is tagged with Sanger’s reagent. Understanding the inherent differences between this SNAr reaction and other nucleophilic substitution reactions (SN1 and SN2) can be challenging for students learning organic chemistry. Here, both electrostatic potential (ESP) maps and natural bond orbital (NBO) analyses are employed to visualize and conceptualize Sanger’s key observation of the difference in reactivity between 2,4-dinitrochlorobenzene and 2,4-dinitrofluorobenzene. The utility of this method is extended to compare the reactivity of a series of halobenzenes for SNAr fluorination, a widely used reaction in pharmaceutical and medicinal fields. In combination with experimental results from the literature, the ESP maps and NBO analyses are consistent with and provide excellent corroboration with the reactivity of different substrates toward SNAr reactions.
IMPORTANCE: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the ...driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)–associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology. OBJECTIVE: To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS. DESIGN, SETTING, AND PARTICIPANTS: This multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort. MAIN OUTCOME AND MEASURES: Plasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling. RESULTS: Of 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean SD, 0.57 0.43 pg/mL) or FTP PET (mean SD, 0.75 0.30 pg/mL) to concentrations comparable to control individuals with AD (mean SD, 0.72 0.37), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P < .001) and FTP PET of 0.93 (95% CI, 0.83-1.00; P < .001). At baseline, individuals with CBS-AD (n = 12), defined by a PET-validated plasma p-tau217 cutoff 0.25 pg/mL or greater, had increased temporoparietal atrophy at baseline compared to individuals with CBS-FTLD (n = 39), whereas longitudinally, individuals with CBS-FTLD had faster brainstem atrophy rates. Individuals with CBS-FTLD also progressed more rapidly on a modified version of the PSP Rating Scale than those with CBS-AD (mean SD, 3.5 0.5 vs 0.8 0.8 points/year; P = .005). CONCLUSIONS AND RELEVANCE: In this cohort study, plasma p-tau217 had excellent diagnostic performance for identifying Aβ or FTP PET positivity within CBS with likely underlying AD pathology. Plasma P-tau217 may be a useful and inexpensive biomarker to select patients for CBS clinical trials.
Hexanucleotide repeat expansion in C9orf72 represents the most common genetic cause of familial and sporadic behavioural variant frontotemporal dementia. Previous studies show that some C9orf72 ...carriers with behavioural variant frontotemporal dementia exhibit distinctive atrophy patterns whereas others show mild or undetectable atrophy despite severe behavioural impairment. To explore this observation, we examined intrinsic connectivity network integrity in patients with or without the C9orf72 expansion. We studied 28 patients with behavioural variant frontotemporal dementia, including 14 C9orf72 mutation carriers (age 58.3 ± 7.7 years, four females) and 14 non-carriers (age 60.8 ± 6.9 years, four females), and 14 age- and sex-matched healthy controls. Both patient groups included five patients with comorbid motor neuron disease. Neuropsychological data, structural brain magnetic resonance imaging, and task-free functional magnetic resonance imaging were obtained. Voxel-based morphometry delineated atrophy patterns, and seed-based intrinsic connectivity analyses enabled group comparisons of the salience, sensorimotor, and default mode networks. Single-patient analyses were used to explore network imaging as a potential biomarker. Despite contrasting atrophy patterns in C9orf72 carriers versus non-carriers, patient groups showed topographically similar connectivity reductions in the salience and sensorimotor networks. Patients without C9orf72 expansions exhibited increases in default mode network connectivity compared to controls and mutation carriers. Across all patients, behavioural symptom severity correlated with diminished salience network connectivity and heightened default mode network connectivity. In C9orf72 carriers, salience network connectivity reduction correlated with atrophy in the left medial pulvinar thalamic nucleus, and this region further showed diminished connectivity with key salience network hubs. Single-patient analyses revealed salience network disruption and default mode network connectivity enhancement in C9orf72 carriers with early-stage or slowly progressive symptoms. The findings suggest that patients with behavioural variant frontotemporal dementia with or without the C9orf72 expansion show convergent large-scale network breakdowns despite distinctive atrophy patterns. Medial pulvinar degeneration may contribute to the behavioural variant frontotemporal dementia syndrome in C9orf72 carriers by disrupting salience network connectivity. Task-free functional magnetic resonance imaging shows promise in detecting early-stage disease in C9orf72 carriers and may provide a unifying biomarker across diverse anatomical variants.
Current methods of determining whether a blog is active or abandoned tend to rely on simple rules, such as identifying whether it has been posted to within the last 7 or 30 days. Individual bloggers ...vary widely in their posting activity levels, however, and so using such fixed cutoffs can result in both misses (calling active blogs "abandoned") and false positives (calling abandoned blogs "active"). We suggest using an alternative metric that varies the cutoff date according to the properties of each individual blog, and show how its results relate to those of the standard 30-day active metric. From our initial analysis, we believe that such a metric offers a more accurate representation of the intuitive notion of blog activity.
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