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91.
Functional connectivity‐based parcellation of amygdala using self‐organized mapping: A data driven approach
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The overall goal of this work is to demonstrate how resting state functional magnetic resonance imaging (fMRI) signals may be used to objectively parcellate functionally heterogeneous subregions of the human amygdala into structures characterized by similar patterns of functional connectivity. We hypothesize that similarity of functional connectivity of subregions with other parts of the brain can be a potential basis to segment and cluster voxels using data driven approaches. In this work, self‐organizing map (SOM) was implemented to cluster the connectivity maps associated with each voxel of the human amygdala, thereby defining distinct subregions. The functional separation was optimized by evaluating the overall differences in functional connectivity between the subregions at group level. Analysis of 25 resting state fMRI data sets suggests that SOM can successfully identify functionally independent nuclei based on differences in their inter subregional functional connectivity, evaluated statistically at various confidence levels. Although amygdala contains several nuclei whose distinct roles are implicated in various functions, our objective approach discerns at least two functionally distinct volumes comparable to previous parcellation results obtained using probabilistic tractography and cytoarchitectonic analysis. Association of these nuclei with various known functions and a quantitative evaluation of their differences in overall functional connectivity with lateral orbital frontal cortex and temporal pole confirms the functional diversity of amygdala. The data driven approach adopted here may be used as a powerful indicator of structure–function relationships in the amygdala and other functionally heterogeneous structures as well. Hum Brain Mapp 35:1247–1260, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
92.
Functional connectivity among brain regions has been investigated via an analysis of correlations between regional signal fluctuations recorded in magnetic resonance (MR) images obtained in a steady state. In comparison with studies of functional connectivity that utilize task manipulations, the analysis of correlations in steady state data is less susceptible to confounds arising when functionally unrelated brain regions respond in similar ways to changes in task. A new approach to identifying interregional correlations in steady state data makes use of two independent data sets. Regions of interest (ROIs) are defined and hypotheses regarding their connectivity are generated in one data set. The connectivity hypotheses are then evaluated in the remaining (independent) data set by analyzing low frequency temporal correlations between regions. The roles of the two data sets are then reversed and the process repeated, perhaps multiple times. This method was illustrated by application to the language system. The existence of a functional connection between Broca's area and Wernicke's area was confirmed in healthy subjects at rest. An increase in this functional connection when the language system was actively engaged (when subjects were continuously listening to narrative text) was also confirmed. In a second iteration of analyses, a correlation between Broca's area and a region in left premotor cortex was found to be significant at rest and to increase during continuous listening. These findings suggest that the proposed methodology can reveal the presence and strength of functional connections in high-level cognitive systems. 相似文献
93.
Outcome after cardiac arrest during acute myocardial infarction 总被引:2,自引:0,他引:2
R J Goldberg J M Gore C I Haffajee J S Alpert J E Dalen 《The American journal of cardiology》1987,59(4):251-255
A community-wide study of acute myocardial infarction (AMI) was conducted in all 16 acute-care general hospitals in the Worcester, Massachusetts, metropolitan area during the years 1975, 1978, 1981 and 1984. The in-hospital and long-term prognoses of 667 patients with AMI complicated by cardiac arrest (CA) was compared with that of 2,596 AMI patients without CA. The incidence of CA complicating AMI was similar (21%) during each of the 4 study years. Among patients with AMI who had CA, 36% had CA within the first day of hospitalization and 48% within the first 2 days. The in-hospital case-fatality rate was much higher for AMI patients with CA (78%) than for those without CA (4%) (p less than 0.001). For patients discharged alive from the hospital, a trend toward a higher mortality rate was seen at 1 and 2 years after hospital discharge for patients with CA; however, long-term survival rates were not significantly different between AMI patients with and without CA. When time of occurrence of CA relative to in-hospital survival was examined, patients with early CA (within 1 day or within 2 days of hospital admission) had a significantly greater in-hospital survival (39% and 34%) than did those with late CA (after 1 day or after 2 days) (13% and 12%). Similarly, patients discharged from the hospital after early CA had a significantly better chance of long-term survival than patients discharged after late CA. 相似文献
94.
Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models
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Victoria L Bridgeman Peter B Vermeulen Shane Foo Agnes Bilecz Frances Daley Eleftherios Kostaras Mark R Nathan Elaine Wan Sophia Frentzas Thomas Schweiger Balazs Hegedus Konrad Hoetzenecker Ferenc Renyi‐Vamos Elizabeth A Kuczynski Naveen S Vasudev James Larkin Martin Gore Harold F Dvorak Sandor Paku Robert S Kerbel Balazs Dome Andrew R Reynolds 《The Journal of pathology》2017,241(3):362-374
Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. 相似文献
95.
Magnetic resonance imaging measurements of the apparent rate of water diffusion in tumors are sensitive to variations in tissue cellularity, which have been shown useful for characterizing tumors and their responses to treatments. However, because of technical limitations on most MRI systems, conventional pulse gradient spin echo (PGSE) methods measure relatively long time scales, during which water molecules may encounter diffusion barriers at multiple spatial scales, including those much greater than typical cell dimensions. As such they cannot distinguish changes on subcellular scales from gross changes in cell density. Oscillating gradient spin echo (OGSE) methods have the potential to distinguish effects on restriction at much shorter time and length scales. Both PGSE and OGSE methods have been studied numerically by simulating diffusion in a three‐dimensional, multicompartment tissue model. The results show that conventional measurements with the PGSE method cannot selectively probe variations over short length scales and, therefore, are relatively insensitive to intracellular structure, whereas results using OGSE methods at moderate gradient frequencies are affected by variations in cell nuclear sizes and can distinguish tissues that differ only over subcellular length scales. This additional sensitivity suggests that OGSE imaging may have significant advantages over conventional PGSE methods for characterizing tumors. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
96.
Hatzakis A Wait S Bruix J Buti M Carballo M Cavaleri M Colombo M Delarocque-Astagneau E Dusheiko G Esmat G Esteban R Goldberg D Gore C Lok AS Manns M Marcellin P Papatheodoridis G Peterle A Prati D Piorkowsky N Rizzetto M Roudot-Thoraval F Soriano V Thomas HC Thursz M Valla D van Damme P Veldhuijzen IK Wedemeyer H Wiessing L Zanetti AR Janssen HL 《Journal of viral hepatitis》2011,18(Z1):1-16
Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority. 相似文献
97.
K. Vashani M. Murugesh G. Hattiangadi G. Gore V. Keer V. S. Ramesh V. Sandur S. J Bhatia 《Diseases of the esophagus》2010,23(1):27-32
Gastroesophageal reflux (GER) with laryngopharyngeal reflux plays a significant role in voice disorders. A significant proportion of patients attending ear, nose, and throat clinics with voice disorders may have gastresophageal reflux disease (GERD). There is no controlled study of the effect of voice therapy on GERD. We assessed the effect of voice therapy in patients with dysphonia and GERD. Thirty‐two patients with dysphonia and GERD underwent indirect laryngoscopy and voice analysis. Esophageal and laryngeal symptoms were assessed using the reflux symptom index (RSI). At endoscopy, esophagitis was graded according to Los Angeles classification. Patients were randomized to receive either voice therapy and omeprazole (20 mg bid) (n = 16, mean [SD] age 36.1 [9.6] y; 5 men; Gp A) or omeprazole alone (n = 16, age 31.8 [11.7] y; 9 men; Gp B). During voice analysis, jitter, shimmer, harmonic‐to‐noise ratio (HNR) and normalized noise energy (NNE) were assessed using the Dr. Speech software (version 4 1998; Tigers DRS, Inc). Hoarseness and breathiness of voice were assessed using a perceptual rating scale of 0–3. Parameters were reassessed after 6 weeks, and analyzed using parametric or nonparametric tests as applicable. In Group A, 9 patients had Grade A, 3 had Grade B, and 1 had Grade C esophagitis; 3 had normal study. In Group B, 8 patients had Grade A, 2 had Grade B esophagitis, and 6 had normal study. Baseline findings: median RSI scores were comparable (Group A 20.0 [range 14–27], Group B 19.0 [15–24]). Median rating was 2.0 for hoarseness and breathiness for both groups. Values in Groups A and B for jitter 0.5 (0.6) versus 0.5 (0.8), shimmer 3.1 (2.5) versus 2.8 (2.0), HNR 23.0 (5.6) versus 23.1 (4.2), and NNE ?7.3 (3.2) versus ?7.2 (3.4) were similar. Post‐therapy values for Groups A and B: RSI scores were 9.0 (5–13; P < 0.01 as compared with baseline) and 13.0 (10–17; P < 0.01), respectively. Ratings for hoarseness and breathiness were 0.5 (P < 0.01) and 1.0 (P < 0.01) and 2.0. Values for jitter were 0.2 (0.0; P = 0.02) versus 0.4 (0.7), shimmer 1.3 (0.7; P < 0.01) versus 2.3 (1.2), HNR 26.7 (2.3; P < 0.01) versus 23.7 (3.2), and NNE ?12.3 (3.0, P < 0.01) versus ?9.2 (3.4; P < 0.01). Improvement in the voice therapy group was significantly better than in patients who received omeprazole alone. Dysphonia is a significant problem in GER. Treatment for GER improves dysphonia, but in addition, voice therapy enhances the improvement. 相似文献
98.
Adam Danquah Kate Limb Melanie Chapman Carrie Burke Andrea Flood Sarah Gore Kara Greenwood Kelsey Healey William Kerr Reid Jan Kilroy Huma Lacey Caroline Malone Michelle Perkin Dougal Julian Hare 《Journal of Applied Research in Intellectual Disabilities》2009,22(4):395-399
Background Self‐injurious behaviour (SIB) is among the most serious problems faced by intellectual disability services. It is very difficult to treat and can become a chronic problem. Method Information on a number of variables was collected through a survey of service‐users identified as displaying SIBs. Clinical opinion and a literature review guided the selection of potential predictors of continued SIB. Univariate statistical analyses were used to investigate associations between continued SIB and each of the variables identified. Variables shown to have a significant association with continued SIB were subjected to a multivariate analysis to isolate those variables that still predicted continued SIB once the influence of the others had been accounted for. Results Two factors, self‐biting and verbal ability, were found to independently predict continued SIB. Conclusion The results have implications for intellectual disability services, in terms of the importance of multidisciplinary team working, training and guidelines for problem management. 相似文献
99.
Pain H Gore S McLellan DL 《International journal of rehabilitation research. Internationale Zeitschrift für Rehabilitationsforschung. Revue internationale de recherches de réadaptation》2000,23(2):75-80
Children who fail to develop postural skills within a normal time scale are prescribed special seating to position them appropriately. For children to derive benefit from such seating, they must use it at home as well as in therapy sessions. A study was undertaken to explore the opinions of therapists and parents concerning the effectiveness and acceptability of a sample of special seating available on the UK market for young children. Each of the ten chairs selected to represent the range of possible styles and features was tested by 12 or 16 children in their homes (total sample of 40) for a week each, and four therapy centres for a fortnight each. Results obtained from these two populations were compared to determine whether chair features considered useful differed when used in a therapy centre or family home. Parents' rating for overall usefulness was affected by their perception of the child's comfort, as well as the child's posture, the level of support the chair offered, and other factors. Therapists' response, in contrast, seemed to be mainly influenced by the quality of posture children achieved in the chair. 相似文献
100.
F. Y. Ahmed G. A. Leonard R. A'Hern A. E. Taylor A. Lorentzos H. Atkinson J. Moore M. C. Nicolson P. G. Riches M. E. Gore 《British journal of cancer》1996,74(7):1109-1113
We have examined the efficacy, toxicity and host immunological response of two different dose schedules of interleukin 2 (IL-2) given subcutaneously, daily for 3 months in patients with renal cell carcinoma (RCC) or metastatic melanoma (MM). We also examined the effect of adding the immune modulator levamisole to the two different schedules of IL-2. Thirty-nine patients were entered into two sequential phase I/II studies. Eighteen patients entered study 1 and were randomised to receive IL-2, 3 x 10(6) IU m-2 day-1, subcutaneously for 3 months with or without levamisole 50 mg t.d.s. p.o. on days 1-3 on alternate weeks. Twenty-one patients entered study 2 and were randomised to receive 5.4 x 10(6) IU m-2 day-1 subcutaneously for 3 months with or without levamisole 50 mg t.d.s. p.o. on days 1-3 on alternate weeks. Blood was taken for peripheral blood lymphocyte (PBL) phenotype analysis, and measurement of IL-2, soluble IL-2 receptor (sIL-2R) and neopterin concentration. Two patients with metastatic melanoma, one in each study, responded (11.8%); both received IL-2 alone. Observations of immunological parameters showed that treatment with subcutaneous IL-2 resulted in a significant rise in the percentage of PBLs bearing CD25, CD3/HLA-DR, CD56 and levels of IL-2 receptor and neopterin. The total white blood cell count (WBC) and total lymphocyte count rose significantly on day 18 compared with pretreatment levels. The addition of levamisole to either IL-2 schedule resulted in no significant changes in any immunological parameters. This study illustrates that prolonged subcutaneous IL-2 can be given safely in the outpatient setting. There was no evidence that levamisole acts as an immunomodulator in this study. 相似文献