Brain functional connectivity has been shown to change over time during resting state fMRI experiments. Close examination of temporal changes have revealed a small set of whole-brain connectivity ...patterns called dynamic states. Dynamic functional network connectivity (dFNC) studies have demonstrated that it is possible to replicate the dynamic states across several resting state experiments. However, estimation of states and their temporal dynamicity still suffers from noisy and imperfect estimations. In regular dFNC implementations, states are estimated by comparing connectivity patterns through the data without considering time, in other words only zero order changes are examined. In this work we propose a method that includes first order variations of dFNC in the searching scheme of dynamic connectivity patterns. Our approach, referred to as temporal variation of functional network connectivity (tvFNC), estimates the derivative of dFNC, and then searches for reoccurring patterns of concurrent dFNC states and their derivatives. The tvFNC method is first validated using a simulated dataset and then applied to a resting-state fMRI sample including healthy controls (HC) and schizophrenia (SZ) patients and compared to the standard dFNC approach. Our dynamic approach reveals extra patterns in the connectivity derivatives complementing the already reported state patterns. State derivatives consist of additional information about increment and decrement of connectivity among brain networks not observed by the original dFNC method. The tvFNC shows more sensitivity than regular dFNC by uncovering additional FNC differences between the HC and SZ groups in each state. In summary, the tvFNC method provides a new and enhanced approach to examine time-varying functional connectivity.
Deficits in the connectivity between brain regions have been suggested to play a major role in the pathophysiology of schizophrenia. A functional magnetic resonance imaging (fMRI) analysis of ...schizophrenia was implemented using independent component analysis (ICA) to identify multiple temporally cohesive, spatially distributed regions of brain activity that represent functionally connected networks. We hypothesized that functional connectivity differences would be seen in auditory networks comprised of regions such as superior temporal gyrus as well as executive networks that consisted of frontal-parietal areas. Eight networks were found to be implicated in schizophrenia during the auditory oddball paradigm. These included a bilateral temporal network containing the superior and middle temporal gyrus; a default-mode network comprised of the posterior cingulate, precuneus, and middle frontal gyrus; and multiple dorsal lateral prefrontal cortex networks that constituted various levels of between-group differences. Highly task-related sensory networks were also found. These results indicate that patients with schizophrenia show functional connectivity differences in networks related to auditory processing, executive control, and baseline functional activity. Overall, these findings support the idea that the cognitive deficits associated with schizophrenia are widespread and that a functional connectivity approach can help elucidate the neural correlates of this disorder.
Introduction: Auditory hallucinations or voices are experienced by 75% of people diagnosed with schizophrenia. We presumed that auditory cortex of schizophrenia patients who experience hallucinations ...is tonically "tuned" to internal auditory channels, at the cost of processing external sounds, both speech and nonspeech. Accordingly, we predicted that patients who hallucinate would show less auditory cortical activation to external acoustic stimuli than patients who did not. Methods: At 9 Functional Imaging Biomedical Informatics Research Network (FBIRN) sites, whole-brain images from 106 patients and 111 healthy comparison subjects were collected while subjects performed an auditory target detection task. Data were processed with the FBIRN processing stream. A region of interest analysis extracted activation values from primary (BA41) and secondary auditory cortex (BA42), auditory association cortex (BA22), and middle temporal gyrus (BA21). Patients were sorted into hallucinators (n = 66) and nonhallucinators (n = 40) based on symptom ratings done during the previous week. Results: Hallucinators had less activation to probe tones in left primary auditory cortex (BA41) than nonhallucinators. This effect was not seen on the right. Discussion: Although "voices" are the anticipated sensory experience, it appears that even primary auditory cortex is "turned on" and "tuned in" to process internal acoustic information at the cost of processing external sounds. Although this study was not designed to probe cortical competition for auditory resources, we were able to take advantage of the data and find significant effects, perhaps because of the power afforded by such a large sample.
In the UK, kidneys are exchanged between centres on the basis of matching for HLA. We analysed various factors that might affect graft outcome to establish whether exchange of kidneys on this basis ...remains valid.
6363 primary cadaveric renal transplants carried out in 23 centres in the UK between 1986 and 1993 were used in the analysis. 6338 (99·6%) patients who underwent transplantation were followed up at 1 year. 5-year follow-up data were available for 2907 (97·8%) of the 2972 patients who survived to 5 years. We made random checks to validate the data. A multifactorial analysis with Cox's proportional hazards models was used to analyse factors that had a possible effect on graft outcome. To ensure that the analysis of matching was constant during the 8-year study, our analysis was based on the HLA antigens used for organ exchange (11 A locus antigens, 27 B locus antigens, and 12 DR locus antigens). We assessed overall outcome at 5 years and during three periods after transplantation at: 0–3 months, 3–36 months, and after 36 months.
The following factors were significantly associated with graft outcome in the multifactorial analysis: year of graft, age of donor, age of recipient, whether the recipient had diabetes, cause of donor's death, cold ischaemic time, transport of kidneys, transplant centre, and matching for HLA. The best outcome was achieved with kidneys that had no mismatches at HLA-A, HLA-B, and HLA-DR loci (000 mismatches). The next most favourable outcome was achieved with one mismatch at either A or B loci or one mismatch at both the A and B, but no mismatch at the DR locus (100, 010, or 110 mismatches). Age of the donor and recipient had a significant effect on transplant outcome: older age was associated with increased risk of graft failure.
Various factors affect the outcome of primary cadaveric renal transplantation, particularly the age of the donor and the recipient. However, the effect of matching for HLA remains a strong one and fully justifies the continuing policy in the UK of exchanging kidneys on the basis of HLA matching, especially to recipients when there is a 000 mismatch for HLA between donor and recipient. On the basis of this analysis, a new allocation scheme for kidneys was introduced in the UK in 1998. During the first 9 months of the scheme, there has been a doubling of the number of HLA-000 mismatched kidneys transplanted.
Nanoindentation studies on Cu–Ti–Zr–Ni–Si–Sn bulk metallic glasses Mukhopadhyay, N.K.; Belger, A.; Paufler, P. ...
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
03/2007, Letnik:
449
Journal Article, Conference Proceeding
Recenzirano
In the present investigation, Cu
47Ti
33Ni
6Sn
2Si
1 (numbers indicate at.%) bulk metallic glass (BMG), fabricated by injection casting has been used for indentation experiments. Microindentation and ...nanoindentation tests were conducted to study the indentation responses of this material. The nanohardness and the Young's modulus were calculated following the standard procedure in literature. Around the indent, shear bands can be clearly observed under scanning electron microscopy examination. Atomic-force microscopy shows the pile of the material in a step-wise manner. The thinned sample near the indent shows the evolution of nanocrystals (∼20–30
nm) by transmission electron microscopy. During nanoindentation (in single- and multi-indent mode) experiments, the load–displacement
P–
h curves show displacement bursts, which are also known as pop-ins or serrations. The total displacement during indentation can be accounted for by sum total effect of the individual displacement of all the displacement-bursts observed in the
P–
h curve. Thus the plastic deformation of this glassy material appears to proceed in a discrete manner unlike ductile metallic alloys.
Le but de cette étude était de mesurer subjectivement et objectivement la charge de travail et le niveau de performance parmi des radiooncologues réalisant une tache informatisée, avant et après ...l’administration d’une session de neurofeedback. Huit participants ont été recrutés pour cette étude pilote. La charge de travail était évaluée subjectivement en utilisant le questionnaire NASA Task-Load-Index (NASA-TLX), et objectivement en utilisant l’analyse de données par électroencéphalographie. Les performances ont été évaluées subjectivement en utilisant un questionnaire d’état de « flow », et objectivement en se basant sur le temps de complétion du test et la performance basée sur les erreurs. Les différences statistiques entre les scores de la période pré- et post-intervention du i) NASA-TLX, du temps de complétion du test et de la performance basée sur les erreurs ont été évalué en utilisant des test t pour des échantillons appariés ; ii) la performance perçue telle que quantifiée par le questionnaire d’état de flow a été évaluée en utilisant le test de rangs signés de Wilcoxon ; iii) et les changements EEG pré- et post-intervention dans les lobes temporaux, acquis tout au long de la réalisation de la tâche, ont été mesurés par l’analyse de variance (ANOVA). Les analyses ont indiqué une réduction significative dans le NASA-TLX (p=0.01) ; un accroissement significatif de la puissance spectrale Theta (p<0.01), et une réduction dans la bande de puissance high-Alpha/low-Beta (p<0.01), suggérant une amélioration de la performance de traitement d’information ; et des améliorations significatives de la performance subjective (questionnaire d’état de flow : valeur de p<0.001). Aucune différence significative n’a été trouvée pour les mesures objectives de performance continues (temps de complétion de la tâche, performance basée sur les erreurs ; p>0.05). Une future recherche est nécessaire pour quantifier davantage l’impact du neurofeedback sur la charge de travail et la performance des radiooncologues.
Introduction: Auditory hallucinations are a hallmark symptom of schizophrenia. The neural basis of auditory hallucinations was examined using data from a working memory task. Data were acquired ...within a multisite consortium and this unique dataset provided the opportunity to analyze data from a large number of subjects who had been tested on the same procedures across sites. We hypothesized that regions involved in verbal working memory and language processing would show activity that was associated with levels of hallucinations during a condition where subjects were rehearsing the stimuli. Methods: Data from the Sternberg Item Recognition Paradigm, a working memory task, were acquired during functional magnetic resonance imaging procedures. The data were collected and preprocessed by the functional imaging biomedical informatics research network consortium. Schizophrenic subjects were split into nonhallucinating and hallucinating subgroups and activity during the probe condition (in which subjects rehearsed stimuli) was examined. Levels of activation from contrast images for the probe phase (collapsed over levels of memory load) of the working memory task were also correlated with levels of auditory hallucinations from the Scale for the Assessment of Positive Symptoms scores. Results: Patients with auditory hallucinations (relative to nonhallucinating subjects) showed decreased activity during the probe condition in verbal working memory/language processing regions, including the superior temporal and inferior parietal regions. These regions also showed associations between activity and levels of hallucinations in a correlation analysis. Discussion: The association between activation and hallucinations scores in the left hemisphere language/working memory regions replicates the findings of previous studies and provides converging evidence for the association between superior temporal abnormalities and auditory hallucinations.
This systematic literature review and network meta-analysis evaluated the efficacy and safety of sintilimab + pemetrexed + platinum versus US FDA-approved/National Comprehensive Cancer ...Network-recommended immune checkpoint inhibitor (ICI) combination therapies for untreated advanced/metastatic non-squamous non-small-cell lung cancer without
/
aberrations.
Bayesian network meta-analysis was the base-case analysis and included assessment of fixed and random effects, and independent and simultaneous models, adjusting for baseline risk (placebo response). Chemotherapy was the common comparator.
Sintilimab + pemetrexed + platinum was associated with significantly longer progression-free survival than atezolizumab + platinum + nab-paclitaxel (hazard ratio HR: 0.57; 95% credible interval CrI: 0.40-0.82) and nivolumab + ipilimumab + pemetrexed + platinum (HR: 0.66; 95% CrI: 0.48-0.92). Sintilimab + pemetrexed + platinum and pembrolizumab + pemetrexed + platinum showed comparable progression-free survival (HR: 0.96; 95% CrI: 0.71-1.30). There was no significant difference in overall survival (HR range: 0.61-0.81) or overall response rates (odds ratio OR range: 0.29-0.75) between sintilimab + pemetrexed + platinum and the other ICI combinations. The incidence of high-grade adverse events was higher with sintilimab + pemetrexed + platinum than with nivolumab + ipilimumab (OR: 0.46; 95% CrI: 0.33-0.64) or without chemotherapy (OR: 0.25; 95% CrI: 0.19-0.34), with no significant difference between sintilimab + pemetrexed + platinum and the other ICI combinations.
Sintilimab + pemetrexed + platinum showed comparable efficacy and safety versus US standard-of-care first-line ICI combinations for advanced/metastatic non-squamous non-small-cell lung cancer.
To compare the incidence and persistence of tardive dyskinesia between patients diagnosed with schizophrenia (ICD-10 and/or DSM-IV) who were treated with second-generation antipsychotics and ...first-generation antipsychotics in routine clinical practice.
The European Schizophrenia Outpatient Health Outcomes (SOHO) study is a 3-year, prospective, observational study. Each country had a start date for patient enrollment before October 2000. All enrollment was completed by June 30, 2001. A simple, global measure of tardive dyskinesia was rated by participating clinicians. For the current analysis, data at baseline, 3 months, and 6 months were analyzed using a generalized estimating equation model.
Second-generation antipsychotics conferred a lower risk for tardive dyskinesia at 6 months than first-generation antipsychotics (0.9% vs. 3.8%, odds ratio OR = 0.29, 95% confidence interval CI = 0.18 to 0.46). In addition, patients with tardive dyskinesia at baseline who were receiving second-generation antipsychotics were less likely than patients receiving first-generation antipsychotics to have tardive dyskinesia symptoms at 6 months (43.6% vs. 60.8%, OR = 0.50, 95% CI = 0.30 to 0.85). A sensitivity analysis suggested no bias related to pharmaceutical industry financial support.
The results suggest that the relative advantage of second-generation antipsychotics in terms of lower rates of incidence and persistence of tardive dyskinesia, observed in technical randomized controlled trials, generalizes to routine clinical care.
Single crystals of Zn–Mg–Er and Zn–Mg–Ho icosahedral phases were grown from the melt using the liquid encapsulated top seeded solution growth technique. The fivefold planes of these as-grown single ...crystals were polished and used for the present nanoindentation studies using Hysitron triboscope attached to an atomic force microscope with a maximum load up to 16
mN. The reduced Young's modulus (
E
r) and nanohardness (
H) were found to be 135
±
10
GPa and 8.5
±
0.2
GPa for the F-type Zn
65Mg
25Er
10 quasicrystal whereas for the P-type Zn
74Mg
15Ho
11 quasicrystal (QC) these were 135
±
10
GPa and 7.8
±
0.2
GPa, respectively. Using the appropriate constants, the average
E in both the quasicrystalline alloys was estimated as 140
±
10
GPa. The elastic and plastic deformation characteristics in load–displacement,
F–
h, curve appears to be identical in both the QC phases. The peculiarity in the load–displacement curves, in terms of pop-ins were observed frequently. AFM images showed the steps in the pile-up material which can be identified as shear bands and correlated with the pop-ins. The first pop-in was observed in the load range of 70
μN in case Zn–Mg–Ho and 84
μN in case of Zn–Mg–Er QC. The contact pressure,
p, turns out to be 13
GPa for Zn–Mg–Ho and 18
GPa for Zn–Mg–Er QC. The maximum shear stress under the indent,
τ
Tresca is found to vary from 6 to 8
GPa, which is close to the theoretical shear strength of this material (∼
E/20). The energy required for the indentation was determined from the first pop-ins and it turned out to be 0.88
eV/atom, close to the thermal energy required for deformation of quasicrystals. Thus the ‘pop-ins’ are attributed to the elastic-plastic transition during indentation.
PDF
