Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the ...neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).
To determine whether amyloid deposition, as assessed by PET imaging with the beta-amyloid-binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.
Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.
Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.
Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that beta-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.
Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry has emerged as a reliable technique to identify molds involved in human diseases, including dermatophytes, ...provided that exhaustive reference databases are available. This study assessed an online identification application based on original algorithms and an extensive in-house reference database comprising 11,851 spectra (938 fungal species and 246 fungal genera). Validation criteria were established using an initial panel of 422 molds, including dermatophytes, previously identified via DNA sequencing (126 species). The application was further assessed using a separate panel of 501 cultured clinical isolates (88 mold taxa including dermatophytes) derived from five hospital laboratories. A total of 438 (87.35%) isolates were correctly identified at the species level, while 26 (5.22%) were assigned to the correct genus but the wrong species and 37 (7.43%) were not identified, since the defined threshold of 20 was not reached. The use of the Bruker Daltonics database included in the MALDI Biotyper software resulted in a much higher rate of unidentified isolates (39.76 and 74.30% using the score thresholds 1.7 and 2.0, respectively). Moreover, the identification delay of the online application remained compatible with real-time online queries (0.15 s per spectrum), and the application was faster than identifications using the MALDI Biotyper software. This is the first study to assess an online identification system based on MALDI-TOF spectrum analysis. We have successfully applied this approach to identify molds, including dermatophytes, for which diversity is insufficiently represented in commercial databases. This free-access application is available to medical mycologists to improve fungal identification.
Acquired brain injury (ABI) often leads to persisting somatic, cognitive, and social impairments. Cognitive impairments of processing speed, sustained attention, and working memory are frequently ...reported and may negatively affect activities of daily living and quality of life. Rehabilitation efforts aiming to retrain these cognitive functions have often consisted of computerized training programs. However, few studies have demonstrated effects that transfer beyond the trained tasks. There is a growing optimism regarding the potential usefulness of virtual reality (VR) in cognitive rehabilitation. The research literature is sparse, and existing studies are characterized by considerable methodological weaknesses. There is also a lack of knowledge about the acceptance and tolerability of VR as an intervention method for people with ABI. The present study aims to investigate whether playing a commercially available VR game is effective in training cognitive functions after ABI and to explore if the possible effects transfer into everyday functioning.
One hundred participants (18-65 years), with a verified ABI, impairments of processing speed/attention, and/or working memory, and a minimum of 12 months post injury will be recruited. Participants with severe aphasia, apraxia, visual neglect, epilepsy, and severe mental illness will be excluded. Participants will be randomized into two parallel groups: (1) an intervention group playing a commercial VR game taxing processing speed, working memory, and sustained attention; (2) an active control group receiving psychoeducation regarding compensatory strategies, and general cognitive training tasks such as crossword puzzles or sudoku. The intervention period is 5 weeks. The VR group will be asked to train at home for 30 min 5 days per week. Each participant will be assessed at baseline with neuropsychological tests and questionnaires, after the end of the intervention (5 weeks), and 16 weeks after baseline. After the end of the intervention period, focus group interviews will be conducted with 10 of the participants in the intervention group, in order to investigate acceptance and tolerability of VR as a training method.
This study will contribute to improve understanding of how VR is tolerated and experienced by the ABI population. If proven effective, the study can contribute to new rehabilitation methods that persons with ABI can utilize in a home setting, after the post-acute rehabilitation has ended.
Having established the binary status of nineteen O-type stars located in four Cygnus OB associations, we now determine their fundamental parameters to constrain their properties and their ...evolutionary status. We also investigate their surface nitrogen abundances, which we compare with other results from the literature obtained for galactic O-type stars. Using optical spectra collected for each object in our sample and some UV data from the archives, we apply the CMFGEN atmosphere code to determine their main properties. For the binary systems, we have disentangled the components to obtain their individual spectra and investigate them as if they were single stars. We find that the distances of several presumably single O-type stars seem poorly constrained because their luminosities are not in agreement with the "standard" luminosities of stars with similar spectral types. Therefore, the ages of these stars agree with those, quoted in the literature, of the four associations, except for Cyg OB8 for which the stars seem older than the association itself.
Field observations over a fringing reef at Ipan, Guam, during trade wind and tropical storm conditions are used to assess the transformation of sea and swell energy from the fore reef to the ...shoreline. Parameterizations of wave breaking and bottom friction developed for sandy beaches are found to represent the observed decay in wave energy with an increased friction coefficient. These parameterizations are incorporated into the one-dimensional energy flux balance, which is integrated across the reef to assess the effects of varying tidal range, incident wave height and reef bathymetry on the sea and swell band wave height and wave setup near the shoreline. Wave energy on the reef is strongly depth-limited and controlled by the reef submergence level. Shoreline wave energy increases with incident wave height largely due to the increase in water level from breaking wave setup. Increased tidal levels result in increased shoreline energy, since wave setup is only weakly reduced. The wave height at the shore is shown to be inversely proportional to the width of the reef flat due to dissipation.
To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA).
The AGREE was a 2-year phase IIIb multinational study in early ...(≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout.
Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2.
The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability.
NCT00122382.
We report the discovery of an extensive system of scattered-light echo arclets associated with the recent supernovae in the local neighborhood of the Milky Way: Tycho (SN 1572) and Cassiopeia A. ...Existing work suggests that the Tycho SN was a thermonuclear explosion while the Cas A supernova was a core-collapse explosion. Precise classifications according to modern nomenclature require spectra of the outburst light. In the case of ancient SNe, this can only be done with spectroscopy of their light echo, where the discovery of the light echoes from the outburst light is the first step. Adjacent light echo positions suggest that Cas A and Tycho may share common scattering dust structures. If so, it is possible to measure precise distances between historical Galactic supernovae. Ongoing surveys that alert on the development of bright scattered-light echo features have the potential to reveal detailed spectroscopic information for many recent Galactic supernovae, both directly visible and obscured by dust in the Galactic plane.
Microvascular obstruction within an area of myocardial infarction indicates worse functional recovery and a higher risk of postinfarction complications. After prolonged coronary occlusion, ...contrast-enhanced MRI identifies myocardial infarction as a hyperenhanced region containing a hypoenhanced core. Because the time course of microvascular obstruction after infarction/reperfusion is unknown, we examined whether microvascular obstruction reaches its full extent shortly after reperfusion or shows significant progression over the following 2 days.
Seven dogs underwent 90-minute balloon occlusion of the left anterior descending coronary artery (LAD) followed by reflow. Gadolinium-DTPA-enhanced MRI performed at 2, 6, and 48 hours after reperfusion was compared with radioactive microsphere blood flow (MBF) measurements and myocardial staining to define microvascular obstruction (thioflavin S) and infarct size (triphenyltetrazolium chloride, TTC). The MRI hypoenhanced region increased 3-fold during 48 hours after reperfusion (3.2+/-1.8%, 6.7+/-4.4%, and 9.9+/-3.2% of left ventricular mass at 2, 6, and 48 hours, respectively, P<0.03) and correlated well with microvascular obstruction (MBF <50% of remote region, r=0.99 and thioflavin S, r=0.93). MRI hyperenhancement also increased (21.7+/-4.0%, 24.3+/-4.6%, and 28.8+/-5.1% at 2, 6, and 48 hours, P<0.006) and correlated well with infarct size by TTC (r=0.92). The microvascular obstruction/infarct size ratio increased from 13.0+/-4.8% to 22.6+/-8.9% and to 30.4+/-4.2% over 48 hours (P=0.024).
The extent of microvascular obstruction and the infarct size increase significantly over the first 48 hours after myocardial infarction. These results are consistent with progressive microvascular and myocardial injury well beyond coronary occlusion and reflow.
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The interaction between screw dislocations and vacancies in body-centered cubic metals is investigated using molecular dynamics simulations. For thirteen different classical ...interatomic potentials, materials properties relating to vacancies, dislocations, and the interaction between the two are evaluated. The potentials include six for iron, two for molybdenum, and five for tantalum, and they are a mix of embedded atom method (EAM), modified embedded atom method (MEAM), and angular dependent potential (ADP) styles. A previously unknown behavior was identified during the interaction simulations. Out of the thirteen potentials investigated, ten predict a vacancy on the dislocation core to no longer remain as a discrete point defect, but rather to dissociate along the dislocation line. The structure of the dissociation is dependent on the potential and is characterized here. As this vacancy dissociation alters the core structure of the dislocation, it may prove to be a new mechanism for dislocation pinning and pipe diffusion.
To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and ...information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
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