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Home > Vol 8, No 62 >	Xuan
Published in Oncotarget V8N62, Dec 1, 2017
Altered network efficiency of functional brain networks in patients with breast cancer after chemotherapy
Oncotarget. 2017; 8:105648-105661. https://doi.org/10.18632/oncotarget.22358
Han Xuan, Chen Gan, Wen Li, Zhonglian Huang, Longsheng Wang, Qianqian Jia, Zhendong Chen _ and Huaidong Cheng
Han Xuan1,*, Chen Gan1,*, Wen Li1, Zhonglian Huang1, Longsheng Wang1, Qianqian Jia1, Zhendong Chen1 and Huaidong Cheng1,*
1Department of Oncology, Cancer and Cognition Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
*These authors have contributed equally to this work
Zhendong Chen, email: 1225886738@qq.com
Huaidong Cheng, email: chd1975ay@126.com
Keywords: breast cancer; network; cognitive function; MRI; chemotherapy
Received: July 05, 2017 Accepted: August 17, 2017 Published: November 09, 2017
Objective: To investigate the topological organization of functional brain networks in chemotherapy-treated breast cancer (BC) patients with source memory impairment.
Methods: Twenty-eight patients with BCfollowingchemotherapyand40age-and education-matched healthy controls (HCs) were recruited in the current study. All participants underwent source memory tests and resting-state functional MRI scans. Individual whole-brain functional brain networks were constructed and analyzed using graph-based network approaches.
Results: Compared with the HCs, the BC patients showed lower scores in the source memory tests (P < 0.001).Graph-based analyses revealed that the patients showed higher absolute global and local efficiency (both P < 0.01) but lower normalized global and normalized local efficiency (both P< 0.001) compared with the HCs. Locally, several prefrontal, occipital, and parietal regions exhibited higher nodal efficiency and functional connectivity in the patients(P< 0.05, corrected). Finally, positive correlations were observed between normalized global efficiency and Mini-Mental State Examination scores (r = 0.398, P = 0.036) and between normalized local efficiency and the source memory scores (r = 0.497, P = 0.01) in the patients.
Conclusion: Chemotherapy-treated BC is associated with abnormal organization of large-scale functional brain networks, which could account for source memory dysfunction in patients with BC.
Altered network efficiency of functional brain networks in patients with breast cancer after chemotherapy | Xuan | Oncotarget
Chemotherapy-induced cognitive impairments (CICI) involve multiple cognitive domains including attention, memory, executive function, and information processing speed in patients with cancer during or after chemotherapy. Breast cancer (BC) is one of the most prevalent types of cancer, with a higher incidence, but it also has better treatment outcomes than others. Patients with BC can survive for a long time, and chemotherapy has therefore become an important issue with long-term effects on the life quality of patients with BC. In 2014, experts suggested initiating guidelines for assessment and management of chemobrain [1]. JCO also published a new study on chemobrain, which indicated that chemobrain is one of the most important areas of research [2].However, the neural mechanism underlying BC chemobrain is not currently well established, particularly from a system-level network integrity perspective.
Previous neurophysiological studies have documented that patients with BC after chemotherapy have subjective and objective cognitive damage [3, 4]. However, CICI occurs heterogeneously in BC. A meta-analysis showed that CICI in BC is present in language and visual space [5], while Morean et al.[6]found that it mainly appeared in memory, attention, and social cognition. More recently, several studies found that memory impairment is prominent in CICI in BC, but the degree of damage is specific to different memory components [7]. BC chemobrain is mainly associated with impairment of event-based prospective memory (EBPM) in terms of prospective memory(PM), and with source memory in terms of episodic memory. Overall, these studies collectively suggest that different cognitive domains, rather than a single one, are affected by CICI in patients with BC, indicative of an involvement of multiple functional systems in the disease. This makes network-level studies vital for understanding the neural substrates of CICI in patients with BC.
Brain networks can be derived from different modalities of non-invasive neuroimaging techniques in vivo [8]. Specifically, resting-state functional MRI (rs-fMRI) is a promising tool for mapping intrinsic brain connectivity network sand has been widely applied to various brain disorders [9]. This technique measures spontaneous brain activity as low-frequency fluctuations in blood oxygen level-dependent (BOLD) signals [10], which exhibit coherent temporal dynamics within and across different neuroanatomical systems. Using this technique, Kesler et al. [11]found that BC chemobrain was related to decreased functional connectivity of the default mode network. On a more global scale, Bruno and colleagues [12]showed that whole-brain functional networks exhibited a reduced normalized clustering coefficient for patients with BC receiving chemotherapy. However, the study found no correlation between cognitive decline and the network alterations.
In the present study, we systematically investigated the topological organization of functional brain networks in28patients with BC after chemotherapy and 40 age- and education-matched healthy controls (HCs).Specifically, individual functional brain networks were constructed by calculating interregional functional connectivity of spontaneous brain time series signals among 90 regions of interest (ROIs).Graph-based network efficiency was then calculated to topologically characterize the resultant networks at both global and nodal levels. BC-related alterations in these network properties were further statistically tested. Finally, a correlation analysis was carried out to examine the relationship between network alterations and cognitive performance in the patients.
Between-group differences in demographic and neuropsychological variables
There were no significant differences in age or education between the patient and control groups (both P > 0.05). However, the patients had significantly lower scores on the digit span test, the verbal fluency test, the Mini-Mental State Examination (MMSE) scores, and the source memory task compared to the HCs (all P < 0.001) (Table 1).
Table 1: Demographics and clinical characteristics and cognition of the participants
BC (n=28)
HCs (n=40)
Age(years)
51.46±8.72
Education (years)
9.25±3.22
MMSE
Digit span
Verbal fluency test
Source memory
BC, breast cancer; HCs, healthy controls; MMSE, Mini-Mental State Examination.
Between-group differences in small-world efficiency
The mean correlation matrices of the BC and HC groups are shown in Figure 1. Both groups exhibited small-world organization of their functional brain networks over the whole sparsity range studied (i.e., normalized global efficiency ~ 1 and normalized local efficiency > 1) (Figure 2). Further statistical comparisons of the AUCs revealed that the patients showed significantly increased global (P = 0.007) and local (P < 0.001) efficiency compared with the HCs. However, after the normalization by random networks, these two measures exhibited significantly lower values in the patients compared to the HCs (both P < 0.001) (Table 2).
Figure 1: The mean correlation matrices within each group. HC, healthy control; BC, breast cancer.
Figure 2: Small-world properties of functional brain networks as a function of sparsity. HC, healthy control; BC, breast cancer.
Table 2: Between-group differences in global network measures
HCs (n = 40)
BC (n = 28)
Local efficiencyauc
0.136 ± 0.022
Global efficiencyauc
Normalized local efficiencyauc
Normalized global efficiencyauc
BC, breast cancer; HCs, healthy controls; auc, area under the curve.
We further examined the effect of imbalanced sample numbers between the BC and HC groups (i.e., 28 vs. 40) on the above results. First, we randomly chose 28 HCs from the control group, and computed and recorded the difference in the mean of each network measure between all the BC patients and the subset of HCs. This procedure was iteratively performed 10,000 times to obtain a distribution, which was used to determine whether the between-group network differences derived from all the participants (i.e., 28 BC patients vs. 40 HCs) fell outside its 95% confidence intervals. The results showed that between-group differences of all network derived from all the participants fell within the 95% confidence intervals of the corresponding distributions derived from the balanced sample numbers. Further, we statistically compared network efficiency of the BC patients with each subset of HCs (permutation test), and found significant (P< 0.05) between-group differences in most cases (10,000 out of 10,000 for local efficiency, 9,936 out of 10,000 for global efficiency, 10,000 out of 10,000 for normalized local efficiency, and 10,000 out of 10,000 for normalized global efficiency) with the same altered directions to those derived from all the participants. These findings indicate limited effect of imbalanced sample numbers between the BC and HC groups on the above results.
Between-group differences in nodal efficiency
Figure 3 shows spatial distribution of hubs for each group. In the HC group, we identified 14 hub regions, including 10 association cortex regions, two paralimbic cortex regions and two primary cortex regions. These hubs were mainly located in frontal/prefrontal (the bilateral middle frontal gyri, the opercular part of the right inferior frontal gyrus, the orbital part of the right inferior frontal gyrus, the right rolandic operculum, and the left medial superior frontal gyrus), parietal (the bilateral postcentral gyri, the bilateral inferior parietal, but the supramarginal and angular gyri and the bilateral supramarginal gyri), and temporal (the left superior temporal gyrus and the right temporal pole: superior temporal gyrus) regions. In the BC group, we identified fifteen hub regions, including eight association cortex regions, five paralimbic cortex regions, and two primary cortex regions. These hubs were predominantly located in parietal (the bilateral postcentral gyri, the bilateral superior parietal gyri, the left inferior parietal, but the supramarginal and angular gyri, the right angular gyrus, and the left precuneus), prefrontal (the orbital part of the bilateral superior frontal gyrus, the orbital part of the right middle frontal gyrus, and the bilateral gyrus rectus), and occipital (the bilateral superior occipital gyri and the right middle occipital gyrus) regions. Notably, only three regions were commonly identified as hubs in both groups, including the bilateral postcentral gyrus and the left inferior parietal, but the supramarginal and angular gyri).
Figure 3: Hubs within each group. HC, healthy control; BC, breast cancer. Refer to Table 3 for regional abbreviations.
Further between-group comparisons revealed that nine regions showed increased nodal efficiency in the patients with BC compared to the HCs(Figure 4). The regions included the orbital part of the bilateral superior frontal gyrus, the bilateral gyrus rectus, and the bilateral superior occipital gyrus, the left superior parietal gyrus and the left precuneus, and the right middle occipital gyrus. Notably, all these regions were identified as hubs in the patient group. There were no regions showing decreased nodal efficiency in the patients compared to the HCs.
Figure 4: Increased nodal efficiency in the patients. Refer to Table 3 for regional abbreviations.
Between-group differences in functional connectivity
We identified two connected components that exhibited increased functional connectivity in the patients with BC compared with the HCs (P< 0.001, corrected) (Figure 5). The first component included 22 nodes and 42 edges that were mainly situated in parietal and occipital regions. The other included 13 nodes and 37 edges that were predominantly located in prefrontal regions. It is worth mentioning that all the regions showing increased nodal efficiency described above were included in these two components. No components were found to show significantly decreased functional connectivity in the patients.
Figure 5: Increased functional connectivity in the patients. Refer to Table 3 for regional abbreviations.
Relationship between network measures and neuropsychological variables
Significantly positive correlations were observed between normalized global efficiency and the MMSE scores (r = 0.398, P = 0.036) and between normalized local efficiency and the source memory scores (r = 0.497,P = 0.01) in the patients (Figure 6). Of note, these correlations did not survive after correcting for multiple comparisons (P> 0.05, corrected by the False Discovery Rate procedure). No significant correlations were found between other network/connectivity measures and cognitive variables(all P > 0.05).
Figure 6: Relationship between network efficiency and cognition in the patients. AUC, area under curve; MMSE, Mini-Mental State Examination.
The current study investigated topological organization of functional brain networks of chemotherapy-treated patients with BC by combining rs-fMRI and graph theory methods. We observed that compared with the HCs, the patients had cognitive dysfunction in general cognition, short-term memory, executive function, episodic memory, and prospective memory. Further network analyses revealed that the patients showed abnormal network organization of parallel network efficiency in their brain networks. Moreover, the altered network efficiency was associated with clinical variables of the patients. Locally, several prefrontal, occipital, and parietal regions showed increased nodal efficiency and functional connectivity in the patients. Overall, these findings provide empirical evidence for network dysfunction in survivors of BC that may contribute to disturbances of cognitive functions in these patients.
We found that the patients showed cognitive obstacles in multiple cognitive domains including language, memory, and other cognitive functions. This is consistent with previous studies [13, 14]. Particularly, memory impairment seems to be one of the most prominent features of BC chemobrain. Based on the same cohort of patients, these findings confirm that rather than affecting a single domain, BC chemobrain is related to cognitive dysfunction in multiple domains.
Graph-based network analyses of the human brain are becoming popular in neuroscience, because they can provide valuable information for our understanding of how the wiring diagram of the brain might promote information transfer and processing [15]. Moreover, this analytical framework is becoming more and more popular in atypical populations, because accumulating evidence indicates that many neuropsychiatric diseases are associated with abnormal coordination between regions, indicative of network dysfunction. Here, we applied a graph-based network analysis to BC chemobrain and discovered that although functional brain networks of both groups exhibited small-world organization, absolute global efficiency and local efficiency were significantly increased in the BC group compared to the HC group. Global efficiency reflects integrative information processing between and across remote regions of the brain and is mainly associated with long-range connections. Local efficiency reflects modular information processing or fault-tolerance of a network and is predominantly associated with short-range connections between nearby regions. The increase in absolute global and local efficiency thus suggests that the functional brain networks of the patients are more efficient in favor of information propagation, exchange, and processing at both global and local levels. This is consistent with our subsequent analyses of nodal efficiency and functional connectivity, which revealed increased nodal efficiency and interregional coordination of multiple regions in the patients (see below for further discussions on these increases).However, after normalization by random networks, functional brain networks of the patients showed lower normalized global and normalized local efficiency than the HCs. Normalized network efficiency quantifies the deviation or optimization degree of an actual network from matched random networks that have the same number of nodes and edges and the same degree distribution as the actual brain networks. This normalization procedure is important because it corrects for potential differences in network features between groups, such as degree distribution. Indeed, we found that random networks derived from the patient group had significantly higher network efficiency (global and local) than those derived from the HC group (P< 0.001). This explains why opposite patterns were observed between absolute and normalized network efficiency in revealing BC-related alterations. The opposite patterns are also consistent with our view that absolute efficiency and normalized network efficiency complement each other to fully characterize topological organization of brain networks. Given that the small-world organization reflects an optimal balance between local specialization and global integration, our findings imply a break of the normal balance in BC. This is consistent with a previous study that showed lower normalized clustering coefficients in functional brain networks of patients with BC [12]. Interestingly, the altered network efficiency was related to cognitive impairments in the patients as evidenced by positive correlations between normalized local efficiency and source memory and between normalized global efficiency and the MMSE scores. That is, the lower the normalized network efficiency of the patient's brain, the worse the cognitive performance of the patient. This suggests a neurocognitive significance of small-world network efficiency in monitoring cognitive impairments in patients with BC. It should be noted that the brain-behavior relationships were not corrected for multiple comparisons, and thus the correlations should be explained with cautions. Future studies are warranted to systematically investigate the associations between brain network alterations and cognitive disturbances in BC.
In addition to topological characterization of the whole brain network, we also investigated regional nodal efficiency and interregional functional connectivity. Nodal efficiency measures the extent of information exchange between a given node and all other nodes in a network and therefore reflects the importance or information load of the node [16]. We found that functional brain hubs were mainly located in association and paralimbic cortex regions of prefrontal and parietal lobes for both groups. Most of these regions have been identified as hubs in previous morphological, structural, and functional brain networks [17–23]. Nevertheless, only three hubs were the same between the two groups, suggesting a remarkable redistribution of functional brain hubs in patients with BC. Further, we found that several regions of the frontal, occipital, and parietal lobes exhibited increased nodal efficiency in the patients. These regions were also found to have increased functional connectivity in the patients. Studies employing voxel-based morphometry [24–26]and multimodal MRI techniques [27]found that patients with BC showed decreased gray matter and white matter volume after chemotherapy in the prefrontal cortex, the posterior parietal cortex, the parahippocampal gyrus, the thalamus, the cingulate, and the precuneus. These findings have shown that brain structural changes caused by chemotherapy are mainly inparietal, frontal, and occipital regions [24-26, 28-30]. These brain regions are consistent with those showing increased nodal efficiency and functional connectivity in the patients in the present study. Because it is highly plastic, the brain can adaptively reorganize to maintain normal function by adjusting regional connectivity profiles when some neurons are inefficient or damaged [31]. The increased nodal efficiency and functional connectivity found in the present study thus suggests that the patients' brains add or establish new connections to compensatefor destructive effects caused by the disease. The compensatory increases of functional connectivity further lead to increased absolute network efficiency in the patients as discussed above. Indeed, by summarizing findings from 126 network studies, a recent study showed that hyperconnectivity is a common response of the brain to neurological disruption [32]. One possible reason for the hyperconnectivity is that neurological disruption requires ongoing recruitment of available detour paths, and the hyperconnectivity may be optimally expressed by increasing connections through the most central and metabolically efficient regions [33]. This is consistent with our findings that all the regions showing increased nodal efficiency in the patients were hubs. Nevertheless, the biological mechanism accounting for the observed hyperconnectivity is not clear particularly given relatively few network studies in BC. Future studies may provide deeper insights into this issue by combining multimodal imaging methods (e.g., arterial spin labeling and positron emission tomography) and biochemical techniques. Notably, using a seed-based approach, only decreased functional connectivity was found with the anterior cingulate cortex for BC patients with chemotherapy in a previous study [34]. This discrepancy could be attributable to remarkable differences in the interval between the last chemotherapy and subsequent MRI scan (i.e., with in1 month vs. 36.6 ± 4.4 months) and/or different analytical approaches (e.g., regional level vs. voxel level).
This study has several limitations. First, the sample size is relative small for the current pilot study, which could challenge the generality of the current findings and limit the power to detect more subtle effects. For example, our correlation results did not survive after multiple comparison correction. Moreover, stage IV patients with BC were included in the current study. This may further increase the heterogeneity of the disease status and the pathogenesis among the patients, and thus confound the current findings. Future studies are needed to examine BC-related functional brain network alterations and their associations with cognitive disturbances of the patients by recruiting more clinically homogeneous samples. Second, this study is a cross-sectional study. It is difficult to exclude the possibility that brain networks are heterogeneous before chemotherapy. So far there is no literature reporting on the inherent heterogeneity of brain networks in patients with BC. Future studies may help explain the current findings by investigating brain network dysfunctions before chemotherapy and longitudinal network changes between pre-chemotherapy and post-chemotherapy. Third, the human brain is a complex system with many non-trivial organizational principles. In addition to efficient small-world organization, future studies need to examine other network features in patients with BC, such as rich-club organization, modular structures, and dynamic network evolution. Fourth, this study only explores functional brain networks of CICI in BC. Although accumulating evidence suggests a strong relationship between structural and functional connectivity [35, 36], there is a lack of one-to-one correspondence [37]. Moreover, different topological features are observed between structural and functional brain networks [38]. Thus, a fusion analysis of multimodal neuroimaging data is needed in the future to examine similarities and differences between structural and functional brain networks, to reveal BC-related topological abnormalities. Finally, we note that the patients included in this study are less well-educated than those in previous studies. It is interesting to investigate whether and how BC-related functional brain network alterations depend on different levels of education and thus cognitive reserve of the patients.
In summary, this study provides evidence for brain dysfunction in survivors of BC from the viewpoint of the global organization of brain functional networks, by using rs-fMRI. In addition, we also report for the first time that the brain network changes are correlated to the source memory disorder, which may provide novel implications for the possible mechanisms underlying CICI in BC.
This study is a case-control study. It included 28 patients with breast cancer who underwent postoperative adjuvant chemotherapy in the Department of Oncology of the Affiliated Second Hospital of Anhui Medical University in China from January 2014 to June 2015. Neuropsychological tests and MRI scans were performed one month after the last chemotherapy for the patients. Forty age-matched and education-matched adults (mainly relatives of the breast cancer patients and workers of the same hospital) were recruited through advertisements as control subjects. All subjects were right-handed. All patients were at BC stages I–IV and were treated with six cycles of standard dose TEC chemotherapy (docetaxel 75 mg/m2 intravenous drip d1 (doxorubicin 50 mg/m2 intravenous drip d1; cyclophosphamide 500 mg/m2 intravenous drip d1; 21 days per cycle). The pathology of all patients was infiltrating ductal carcinoma, ECOG 0-1. Chemotherapy regimens and doses for all patients were in accordance with NCCN guidelines. The exclusion criteria included the following: (1) central nervous system radiation or intrathecal therapy; (2) current or past alcohol or drug dependence; (3) neurobehavioral risk factors including neurologic, medical, or psychiatric conditions known to affect brain structure or function, except a history of depression or anxiety; (4) any MRI contraindications; (5) patients with brain metastases; (6) patients with obvious psychological distress and fatigue in terms of the Distress Thermometer and National Cancer Institute Common Toxicity Criteria. The MRI data of all patients were collected within one month after six cycles of chemotherapy. This study was approved by the Research Ethics Review Board of the Second Affiliated Hospital of Anhui Medical University, and written informed consent was obtained from each participant.
Neuropsychological tests
The following neuropsychological tests were administered to all participants: (1) the MMSE to measure global cognitive functions, (2) the verbal fluency (number of animals per minute) test to measure frontal-temporal functions, and (3) the digit span test to estimate short-term memory and executive function, including forward and backward spans.
Source memory tests
There were eight categories of daily-life common objects (fruits, animals, clothing, tools, furniture, transportation tools, stationery and household electrical appliances). Two objects were selected from each category; one was presented with a Jane diagram (selected images from Snodgrass), while the other was presented with content words.
(1) Learning phase: Subjects were visually presented with one content word and one real figure from each category. The participants were then asked to choose another object of the same category and remember it. There were a total of 24 things from eight categories. (2) Testing phase: After 5 minutes of studying, the subjects were randomly presented with48 content words that belonged to eight categories. Of these 48 content words,24 items were learned (content words, real figures, or associated objects). The other 24 objects were interferential. Subjects were asked to make a new (interferential object) or old (learned object) judgment in of the recognition task. Subjects were then asked to make a judgment of the source memory task from the learned object. In addition, subjects were asked to indicate the order of the project presentation in the learning phase (content words, real figures, or associated objects) [39].
Source memory performance
Performance was calculated as correct numbers/total target numbers. All tests were completed by one doctor to eliminate bias.
MRI image acquisition and preprocessing
All MR images were acquired using a Siemens Verio 3.0 T scanner (Siemens, Erlangen, Germany) at the Second Affiliated Hospital Cancer Institute of Anhui Medical University. Functional images were collected using an echo-planar imaging (EPI) sequence with the following acquisition parameters:32 axial slices; repetition time (TR) = 2000ms; echo time (TE) = 30 ms; flip angle (FA) = 9°; slice thickness = 4 mm; no gap; matrix = 64×64; and field of view (FOV) = 220×220 mm2. During the scanning, all participants were instructed to keep their eyes closed, relax their minds, and remain as motionless as possible. The scan lasted for 480 s. Additionally, individual structural images were also acquired for the registration purpose using a T1-weighted gradient echo spiral pulse sequence: 192 axial slices; TR = 1700 ms; TE = 2.98 ms; FA = 9°; slice thickness = 1.0 mm; no gap; matrix = 256×256; and FOV = 256×256 mm2.
All functional data preprocessing, network construction, topological analysis, and statistical comparisons were performed using the GRETNA toolbox [40] based on SPM 8 (http://www.fil.ion.ucl.ac.uk/spm/software/spm8/). First, the first five volumes were removed for each participant to allow for T1 equilibration effects. The remaining images were then corrected for intra-volume time offsets between slices (Sinc interpolation) and inter-volume geometrical displacements due to head motion (six-parameter rigid-body transformation). No participants were excluded based on the criterion of a displacement > 2.5 mm or an angular rotation > 2.5 degree in any direction. There were no significant differences in summary measures of head motion profiles between the patients and controls, including the maximum, root mean square and mean frame-wise displacement (all P > 0.05). Subsequently, all corrected functional images were normalized to the Montreal Neurological Institute (MNI) space using the transformation fields that were derived from tissue segmentation of individual structural images and were resampled to 3-mm isotropic voxels. The normalized images further underwent removal of linear drifts and temporal band-pass filtering (0.01 - 0.08 Hz) to reduce the effects of low-frequency drift and high-frequency physiological noises. Finally, several nuisance signals were regressed out from each voxel's time series to exclude non-neuronal sources, including 24-parameter head motion profiles, white matter signals, cerebrospinal fluid signals and global signals. The whiter matter, cerebrospinal fluid and global signals were derived by averaging signals within white matter, cerebrospinal fluid and whole-brain masks, respectively, in terms of prior probability maps and brain mask file in SPM8 (threshold = 0.8).
Network construction and analysis
Correlation matrix
In the current study, we calculated interregional functional connectivity matrix for each participant at a macroscopic level. First, the cerebrum was divided into 90 ROIs (45 for each hemisphere; Table 3 ) in terms of a prior Anatomic Automatic Labeling atlas [41]. The Anatomic Automatic Labeling atlas is one of the most commonly used one in previous brain network studies [42]. Then, the mean time series was extracted for each ROI by averaging the time series of all voxels within it, therefore resulting in 90 regional mean time series for each participant. The resultant regional mean time series were subsequently correlated (Pearson correlation) with each other and finally generated a 90 × 90 correlation matrix for each participant. The correlation matrices could be modeled as graphs and further topologically characterized by graph theory-based network approaches. In graph theory, a network or graph is composed of nodes and edges, with nodes representing ROIs and edges representing interregional functional connectivity in the current study. Notably, before subsequent network analyses, negative correlations were excluded (set to 0) in all correlation matrices given their ambiguous interpretation [43–45]and distinct connectivity patterns [46].
Table 3: Regions of interest
Superior frontal gyrus, dorsolateral
SFGdor
Middle frontal gyrus, orbital part
ORBmid
Middle frontal gyrus
Inferior frontal gyrus, orbital part
ORBinf
Inferior frontal gyrus, opercular part
IFGoperc
Superior frontal gyrus, medial orbital
ORBsupmed
Inferior frontal gyrus, triangular part
IFGtriang
Gyrus rectus
Rolandic operculum
Supplementary motor area
Anterior cingulate and paracingulate gyri
Superior frontal gyrus, medial
SFGmed
Median cingulate and paracingulate gyri
Cuneus
Posterior cingulate gyrus
Lingual gyrus
Parahippocampal gyrus
PHG
Superior occipital gyrus
Temporal pole: superior temporal gyrus
TPOsup
Middle occipital gyrus
Temporal pole: middle temporal gyrus
TPOmid
Inferior occipital gyrus
Olfactory cortex
Fusiform gyrus
Superior parietal gyrus
AMYG
Inferior parietal, but supramarginal and angular gyri
Caudate nucleus
Supramarginal gyrus
Lenticular nucleus, putamen
Angular gyrus
Lenticular nucleus, pallidum
Precuneus
PCUN
Paracentral lobule
Precental gyrus
PreCG
Superior temporal gyrus
Calcarine fissure and surrounding cortex
Middle temporal gyrus
Postcentral gyrus
PoCG
Inferior temporal gyrus
Heschl gyrus
Superior frontal gyrus, orbital part
ORBsup
Regions of left and right hemispheres are indexed by odd and even numbers, respectively.
Threshold selection
Before the graph theory-based network analysis of the correlation matrices derived above, a thresholding procedure was first used to convert them into binary networks, whose elements were either 0 or 1, indicating the absence or presence of an edge between two nodes, respectively. This was achieved by applying a correlation coefficient threshold to individual correlation matrices such that correlation coefficients greater than the threshold were set to 1, and others were set to 0. However, if the same correlation coefficient threshold was applied to all individual correlation matrices, the resultant networks will have different numbers of edges across participants and particularly between the two groups due to differences in overall connectivity strength of the correlation matrices. This could confound subsequent between-group comparisons of network topology [9, 47]. To address this concern, a subject-specific correlation threshold was used in the current study to ensure that all resultant networks have the same number of edges and network cost by assigning a fixed sparisty, S, which is defined as the ratio of the number of actual edges divided by the maximum possible number of edges in a network. For example, for a given sparsity S = 0.1, only the strongest 10% correlation coefficients were retained and set to 1 for each individual correlation matrix. The sparsity-based thresholding procedure therefore allows examining network organization after ruling out confounding effect of different network costs between groups. However, given the lack of a canonical way to determine a single sparsity, we repeatedly thresholded each correlation matrix to generate binary networks with different sparsity values in a continuous range of 0.05 <S< 0.4 (interval = 0.02). This enabled us to characterize network organization as a function of sparsity and thus minimize potential bias introduced by a precise selection of single sparsity. The inferior limit of the sparsity was determined to guarantee that the resultant networks were estimable for small-worldness [48] and the superior limit was empirically chosen to ensure that resultant networks had sparse properties [16]. Subsequently, we studied the small-world organization and nodal efficiency for all brain networks at each sparsity threshold.
Small-world efficiency
In the current study, we employed both abo efficiency metric (local efficiency and global efficiency) to characterize economical small-world properties of functional brain networks derived above. Compared with conventional small-world parameters of clustering coefficient and characteristic path length [48], the efficiency metric is biologically more sensible and has a number of technical and conceptual advantages. For example, it can represent how efficiently a network exchanges information at local and global levels with a single measure, and deal with either the disconnected or nonsparse graphs or both [16, 49, 50]. Moreover, the efficiency metric has been widely used to study the small-world behavior in previous brain network studies under both normal and pathological conditions [16, 42, 51]. Mathematically, the global efficiency of a network G with N nodes is defined as [50]:
Eglob(G)=1N(N−1)∑i≠j∈G1dij,
where dij is the shortest path length between node i and nodej and is calculated as the smallest number of edges among all possible paths from node i to node j. The global efficiency measures the ability of parallel information transfer over the entire network. The local efficiency of G is calculated as [50]:
Eloc(G)=1N∑i∈GEglob(Gi),
where Eglob(Gi) is the global efficiency of Gi, the subgraph composed of the neighbors of node i (i.e., nodes linked directly to node i). The local efficiency reflects how well the network exchanges information locally or how much the network is fault tolerant.
To determine whether the brain networks were organized in a small-world manner, the global and local efficiency of each participant derived at each sparsity level were normalized by dividing them by the corresponding mean of 100 random networks. The random networks were generated using a topological rewiring algorithm that preserved the same number of nodes, edges and degree distributions as the real brain networks [52, 53]. Typically, a network with approximately equal global efficiency and larger local efficiency (i.e., normalized global efficiency or λ ~ 1 and normalized local efficiency or γ > 1) than matched random networks is said to be small-world [48].
Nodal efficiency
For each node, we calculated the nodal efficiency to capture their roles in the brain network. Specifically, for a given node i in the network G, the nodal efficiency is defined as the average shortest path length between node i and all other nodes in the network [16]:
ei=1N−1∑j≠i∈G1dij,
where dij is the shortest path length between node i and nodej in G. Nodal efficiency reflects the ability of a node to exchange information with the rest of the nodes in the network. Regions with high nodal efficiency are typically considered hubs in the brain. In the current study, regions with nodal efficiency at least one standard deviation above the group mean (across all nodes and participants) were identified as hubs within each group.
Between-group differences
For demographic and clinical variables, between-group differences were examined with two-sample, two-tailed t-tests; these variables included age, education, digit span, verbal fluency test, source memory, item memory, MMSE, retrospective memory(RM) and prospective memory(PM). For network topological measures (global efficiency, local efficiency, normalized global efficiency, normalized local efficiency, and nodal efficiency), we computed their areas under the curve (AUCs, i.e., the integral over the whole sparsity range), which were used to simplify statistical analysis. Specifically, a non-parametric permutation test was used to examine between-group differences in these network measures. In brief, for each metric, we initially calculated the between-group difference in mean values. An empirical distribution of the difference was then obtained by randomly reallocating all values to two groups and re-computing the mean differences between the two randomized groups (10,000 permutations). The 95th percentile points of the empirical distribution were used as critical values in a one-tailed test to determine whether the observed real-group differences occurred by chance. To examine between-group differences in interregional functional connectivity, a network-based statistic (NBS) method[54] was performed. Briefly, a primary threshold (P< 0.01) was applied to the t values (90 × 90 matrix) derived from an edge-by-edge between-group comparison of interregional functional connectivity (two-sample t-test). Among the resultant suprathreshold connections, we identified all connected components and recorded their size (i.e., number of links). To estimate the significance of each identified component, a null distribution of the connected component size was empirically derived by using a permutation approach (10,000 permutations). For each permutation, all subjects were randomly rearranged into two groups, and the same primary threshold (i.e., P< 0.01) was used to filter suprathreshold links in the comparison between the two randomized groups. The size of the maximal connected component among these links was recorded to form the null distribution. Finally, for any connected component of size M that was observed in the comparison of the right grouping, the corrected P value was determined by calculating the proportion of the 10,000 permutations for which the maximal connected component was larger than M. Notably, only connections that were positive in > 80% of all participants were included in the NBS analysis. Hubs, regions showing abnormal nodal efficiency (P < 0.05, Bonferroni corrected), and NBS components showing altered functional connectivity in the patients were visualized on the brain surface using the BrainNet viewer [55].
Relationships between network metrics and cognition
Pearson correlation analysis was used to study the relationships between network metrics/functional connectivity showing significant between-group differences and cognitive variables in the patient group.
BC: Breast cancer; HCs: Healthy controls; rs-fMRI: Resting-state functional Magnetic resonance image; MMSE: Mini-Mental State Examination; CICI: chemotherapy-induced cognitive impairments; EBPM: event-based prospective memory;RM:retrospectivememory;PM: prospective memory;ROIs: regions of interest; AAL: Automated Anatomical Labelling; BOLD: blood oxygen level-dependent; AUC: area under curve.
HX, CG and HDC conceived the study, participated in its design, and coordination, and the search strategy, performed study selection, data extraction, and synthesis, data analysis, and drafted the manuscript, and interpretation of the results. ZLH, WL, QQJ and LSWparticipated in data collection. ZDC and HDC conceived the study, participated in its design and coordination, participated in study selection, and helped to draft the manuscript. All authors read and approved the final manuscript.
This research was supported by the The National Natural Science Foundation of China (No. 81372487).
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Personal Edition of CodeCharge Studio is aimed at single Web developers who may not need all the programming languages offered with the full version of CodeCharge Studio. It is also a good choice for students and novice developers that want to get their "feet wet" without spending a lot of money.
What's included in CodeCharge Studio Personal Edition?
- CCS PE supports single technology chosen by the user: .NET, ASP, PHP, Java or Perl.
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Both the full version and Personal Edition of CodeCharge Studio are distributed as a single executable file. During the 20-day trial period you are evaluating the full version of CodeCharge Studio. At any time during your evaluation you can purchase the CodeCharge Studio or CodeCharge Studio Personal Edition. If you purchase the Personal Edition you will be required to chose your programming language at the time of purchase. After you make the purchase you will receive a serial number that activates your downloaded evaluation version of CodeCharge Studio and re-enables the features specific to the product version you have purchased.
Do I need to choose between C# and VB.NET or JSP and Servlets?
No. If you purchase CodeCharge Studio Personal Edition and select .NET you will be able to work with both C# and VB. If you select Java, your copy of CCS PE will support both JSP and Servlets.
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STAMFORD, Conn, – August 2, 2016 – NBCUniversal's coverage of the Games of the XXXI Olympiad from Rio de Janeiro, Brazil begins tomorrow, Wednesday, August 3, with the kickoff of the women's soccer tournament, featuring six live games across NBCSN and USA Network.
In addition, live coverage of men's soccer group play kicks off on NBCSN on Thursday at Noon ET with Iraq vs. Denmark from Mane Garrincha Stadium. Coverage continues on NBCSN when Neymar leads the team from the Olympics host country of Brazil against South Africa at 3 p.m. ET, immediately followed by a meeting between medal contenders Portugal vs. Argentina at 5 p.m. ET from Olympic Stadium.
Soccer – Sweden vs. South Africa: Sweden takes the field against South Africa at Olympic Stadium in a Group E women's soccer prelim. Sweden fell to France 2-1 in the quarterfinals of the 2012 London Olympics. Canada vs. Australia: The Canadian women's national team looks to build on its 2012 Olympic bronze as they open the Rio tournament with a Group F soccer prelim against Australia at Corinthians Arena in Sao Paulo. In the London semifinals, Canada fell to the eventual champion United States 4-3 in an extra-time thriller. U.S. vs. New Zealand: Carli Lloyd leads the U.S. women as they open play in a Group G soccer prelim against New Zealand at Mineirao Stadium in Belo Horizonte. Four years ago in London, Lloyd tallied both goals in the U.S.'s 2-1 victory over Japan, giving the U.S. its third straight Olympic gold. France vs. Colombia: France and Colombia meet in a Group G women's soccer prelim at Mineirao Stadium in Belo Horizonte. France was shut out by Canada 1-0 in the bronze medal match four years ago in London.
Soccer – Brazil vs. China: Brazil takes on China in a Group E women's soccer prelim at Olympic Stadium. The last Olympic match for the host nation was a 2-0 loss to Japan in the quarterfinals of the 2012 London Games. Zimbabwe vs. Germany: Corinthians Arena in Sao Paulo plays host to Zimbabwe against Germany in a preliminary-round Group F women's soccer match.
Soccer – Brazil vs. China: Brazil takes on China in a Group E women's soccer prelim at Olympic Stadium. The last Olympic match for the host nation was a 2-0 loss to Japan in the quarterfinals of the 2012 London Games. U.S. vs. New Zealand: Carli Lloyd leads the U.S. women as they open play in a Group G soccer prelim against New Zealand at Mineirao Stadium in Belo Horizonte. Four years ago in London, Lloyd tallied both goals in the U.S.'s 2-1 victory over Japan, giving the U.S. its third straight Olympic gold. France vs. Colombia: France and Colombia meet in a Group G women's soccer prelim at Mineirao Stadium in Belo Horizonte. France was shut out by Canada 1-0 in the bronze medal match four years ago in London.
Soccer – Iraq vs. Denmark: Iraq faces Denmark in a Group A men's soccer prelim at Mane Garrincha Stadium in Brasilia. Brazil vs. South Africa: Behind team captain Neymar, the Brazilian men kick off their pursuit of the country's first-ever Olympic gold in a Group A prelim against South Africa. The FC Barcelona forward was held scoreless four years ago in a 2-1 loss to Mexico in the London gold medal final. Portugal vs. Argentina: Two medal contenders clash in a high-stakes prelim as Portugal takes on Argentina in a Group D men's soccer match at Olympic Stadium in Rio de Janeiro. Fiji vs. South Korea: A Group C men's soccer prelim pits South Korea, who topped Japan for bronze in London, against Fiji at Salvador's Fonte Nova Arena. Nigeria vs. Japan: Nigeria plays Japan in preliminary Group B men's soccer action at Amazonia Arena in Manaus. Japan advanced to the 2012 bronze medal match, which it lost 2-0 to South Korea.
Soccer – Iraq vs. Denmark: Iraq faces Denmark in a Group A men's soccer prelim at Mane Garrincha Stadium in Brasilia. Brazil vs. South Africa: Behind team captain Neymar, the Brazilian men kick off their pursuit of the country's first-ever Olympic gold in a Group A prelim against South Africa. The FC Barcelona forward was held scoreless four years ago in a 2-1 loss to Mexico in the London gold medal final. Portugal vs. Argentina: Two medal contenders clash in a high-stakes prelim as Portugal takes on Argentina in a Group D men's soccer match at Olympic Stadium in Rio de Janeiro.


John Meridith Swift was only 14 years old and he was quite impressed by the hypnotist he'd seen. It wasn't surprising that he tried to imitate the man, but, as he discovered with young Nancy next door, he had to give his voice time to mature a little.
He never lost his fascination for the art, however, and much later . . . in his last year at college, he had the opportunity for an interesting experiment. One which caused a young virgin to turn up pregnant; almost costing her life and sanity . . . and John's as well .. .
Desperately, passionately in love with Randy, Jerry though he had found happiness — until he ran headlong into a leather-jacketed band of cruel, lusting wanton, twisted he-women… one of whom wanted Randy even more than he!
Doug Weaver's classic cover art was later reused for Satan Was A Lesbian. Not related to the Spicy Mystery story of the same name.


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10 notecards featuring illuminations from the Prophets, Psalms, Pentateuch, and Wisdom Books volumes of The Saint John's Bible.
Donald Jackson
An internationally respected calligrapher, Donald Jackson is the artistic director and illuminator of The Saint John's Bible. He is a Senior Scribe to Her Majesty Queen Elizabeth's Crown Office at the House of Lords in the United Kingdom, a position in which he is responsible for the creation of official state documents. He is an elected Fellow and past Chairman of the prestigious Society of Scribes and Illuminators. His 30-year retrospective exhibition, Painting with Words, premiered at The Minneapolis Institute of Arts in Minneapolis, Minnesota in August, 1988 and traveled to 13 museums and galleries. Donald Jackson works with a team of theologians and artists from Saint John's University and Abbey on The Saint John's Bible. From his scriptorium in Wales, he oversees scribes, artists, and craftsmen who work with him on the handwriting and illumination of the seven-volume, 1,150-page Bible.
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If you're anything like us, you're not looking forward to losing an hour of sleep Saturday night, but you are excited at any indication that Spring might actually come some day.
The Little Fleet invites you and your kids to enjoy Brenin and his Banjo from 4-7 PM today. Brenin will play some banjo for the kiddos, and then they'll be serving up family dinner. $5 cover includes dinner. Kids are free.
As usual, Joe Wilson & Josh Davis play at the Workshop from 7-10 PM and Don Julin and Billy Strings play from 8-10 at Little Bohemia. No cover for either so get out and enjoy some of TC's finest string players!!
The first Friday of every month is First Friday in the Village. From 5-8 you can enjoy events all through the Village at Grand Traverse Commons. Highlights include a village-wide hot cocoa tasting with a Prize Giveaway, Don Julin & Billy Strings at Left Foot Charley Winery, Awesome Distraction at North Coast Legal, PLC & Re:form Studio (upstairs from Mercato) and Missy Zenker at Mi Farm Market.
TASTES of Black Star Farms gets in on the monthly First Friday fun with their "Savor the Tastes & Flavors" experiential event. This month they will be looking at hang time of grapes and how that influences the character of the wine using their dry and late harvest Rieslings. $3 per person or $5 per couple includes wine & appetizer.
Join chef-educator Nancy Krcek Allen at Lobdell's Restaurant overlooking Grand Traverse Bay for a nine course Spanish tapas, wine & cheese tasting. In addition to a food demo by Nancy, cheese-maker Mary Buschell will share unique cheeses from each region and Shawn Harvey, wine steward from Burritt's Market, will guide you through tasting and pairing Spanish wines. The cost is $75 and you can register online or call (231) 995-1700.
Also Friday are Blackbird Pie Live at The Workshop and the DRAM GIN Infusion Release Party (7- Midnight) at InsideOut/ Outré Lounge.
There's still space available in a 3 hour class from 11-2 on Saturday at NMC that will teach you how to create authentic sushi for your next eating event. Three kinds of sushi are featured: Japanese traditional, California style, and hand-rolled (Temaki-zushi). Chef Misaeng, a native of Japan, guides this hands-on class including tips on ingredient selection, preparation, and serving ideas. Leave with new skills, samples you prepared in class, and your own sushi mat to make sushi at home!
Get a fresh start to your week and go to the Traverse City Farm Market between 10-2. You will find local fresh lettuce, micro-greens, meats, dairy, honey, candles, maple syrup, baked goods, canned goods, cheeses, root vegetables, treats and even gluten free treats.
Join Northern Naturals every Saturday at 3 PM for their Kid-friendly Open Mic and on Saturday night you can join Josh Rose live at The Workshop.
The Little Fleet invites you to the Social Skate at Little Fleet every Sunday through the end of March (as long as the ice holds). Enjoy the ice rink at F&M Park and them head over to the Fleet for free hot chocolate. Spike it for $2!
Bistro Fou Fou hosts the third of a five month series of food & wine dinners exploring five major wine regions in France on Wednesday. You can also head out to Black Star Farms for their Harvest Wine Dinner featuring "Goose & Greens".
On Thursday the TEDX Salon at The Workshop turns its attention to a topic near and dear to our hearts: Water. Hear local luminaries talk about water and the complex issues surrounding it from 4-6 PM on Thursday. Two more Thursday options are the Altasian Wine Dinner at La Becasse in Burdickville featuring Altasian cuisine paired with wines from Chateau Fontaine and Cheese & Beer Pairing at The Little Fleet with Brewery Terra Firma and local Boss Mouse Cheese.
We work hard, we eat hard, and we welcome your support!


Rusty Simmons Feb. 14, 2019 Updated: Feb. 14, 2019 3:21 p.m.
The school-record losing streak continues for the Cal men's basketball team.
This one might have been in as painful a fashion as the Bears have endured during their 13-game skid.
Cal, which led for nearly 31 minutes, was up by as many as 11 points, and was ahead with 76 seconds to play in regulation, fell to UCLA 75-67 in overtime on Wednesday night at Haas Pavilion.
Moses Brown's free throw, just his second make in nine attempts, put UCLA ahead 65-64 with 4:18 left in overtime, and Chris Smith's putback extended the lead to three points with 2½ minutes to play.
Jaylen Hands' free throws made it a five-point game, which seemed insurmountable for a Cal squad that went 1-for-8 with two turnovers in overtime. Sure enough, Hands' free throws in the final 68 seconds iced it.
The Bears (5-19, 0-12 Pac-12) played inspired defense, forcing 19 turnovers and holding an opponent under 40 percent shooting for just the second time this season and for the first time since Hampton shot 31 percent Nov. 13.
But Cal, which got 18 points from Darius McNeill and 15 from Justice Sueing, got beat by 14 on the boards and had no answer for Kris Wilkes. The swingman had 27 points on 5-for-8 3-point shooting for the Bruins (13-12, 6-6).
Cal led for all but 49 seconds of the first half and by as many as 10 points as UCLA got off to a woeful start. Interim head coach Murry Bartow did a full line change 3:07 into the game after the Bruins' starters missed their first eight shots.
It didn't make much difference. UCLA opened 0-for-9 and didn't make its second field goal until the 11:30 mark, when Cal already led 11-2. The Bears extended their advantage to 20-10 on two Sueing free throws with 7:51 left, but the Bruins ran off a 9-0 run to make it a game.
Even though UCLA made just eight baskets and had 13 turnovers on 37 first-half possessions, it went into the locker room chasing only a 34-25 deficit. Sueing converted the technical foul shots off a whistle on Jalen Hill to open the second half with an 11-point edge, and Cal still led by nine with 15 minutes to play.
But, behind three 3-pointers by David Singleton and improved defense, the Bruins erased the deficit in a four-minute span. Chris Smith's 15-foot jumper gave UCLA its first lead (44-43 with 11:05 remaining).
Cal didn't lead again until Grant Anticevich the second of back-to-back turnaround jumpers for a 57-55 advantage with 3:57 on the clock. The Bears were still up by four until Singleton and Wilkes made consecutive 3-pointers to give UCLA a 61-59 lead with 75 seconds to play.
Matt Bradley's free throws with 59.1 seconds left tied it for Cal, but Wilkes responded with a 3-pointer that put the Bruins up 64-61 with 46.7 seconds on the clock. Bradley's corner 3-pointer tied it with 27.6 seconds left, and Wilkes' forced 3-pointer missed as the regulation buzzer sounded to give Cal another chance at its first conference win.


A stylish development of two, three and four-bedroom family houses to buy in Ellesmere Port, just minutes away from the UK's largest designer outlet village.
Macbryde Homes is a family run business, building stunning new award-winning homes of distinction in North Wales and North West England, currently in Conwy, Cheshire, Wirral & Liverpool. Over the last 30 years, Macbryde Homes has established an enviable reputation for designing and building exceptional, high quality homes.


experience the real Belize City!
Belcove Hotel, in the center of downtown Belize City, along the Belize River, is the economic, clean and comfortable choice for you. Family owned and operated, it provides a cozy and friendly atmosphere to all who enter its doors.
If, however, you want to get away from the City, then we can make arrangements for you at our private island getaway. Gallows Point, the legendary home of pirates during the 1600s, can at your request become your personal retreat.
A private 30-minute boat transfer to the north of Belize City takes you to the tranquil island of Gallows Point. Here you can experience the beauty of the cayes, without the hassle of a long ride and crowds of "tourists", plus you can do so at a very economical price.
A non-refundable 10% deposit with the Tropical Travel Association is required in order to confirm your reservation. The 90% balance is due to the hotel upon arrival. In special circumstances Belcove Hotel has the right to apply additional requirements as long as they do so before the 10% deposit is paid.
We're on the river, just above the famous swinging bridge in the heart of the city.
Please fill out the questionnaire below and click "Contact Belcove Hotel"
A representative from Belcove Hotel will get back to you soon.
Belcove Hotel is a member in good standing of Tropical Travel Association.
* Note: For your protection, Tropico will never give your email address to anyone other than a qualified representative from Belcove Hotel, and only then once all arrangements have been made.


Meet with your Instructional Designer and the Media Team to prepare for recording your presentations.
Record your first presentation. Review the guide: Record Your Presentations.
Review your first presentation with the OES media team.
Recording your presentations will continue through the development cycle. Because this portion requires a commitment in time, it is important that you start now.


text:
PAIR WINS LAWSUITS OVER TREE UPKEEP – Vista (2006)
PAIR WINS LAWSUITS OVER TREE UPKEEP—
Mobile-home Park Owners Liable for Tree Damage, Judge Rules
Article by ERIN MASSEY, Staff Writer, North County Times
VISTA, California
A Superior Court judge sided with two elderly women and ruled this week that mobilehome park owners must pay for any tree removal on the park property.
Judge Joe O. Littlejohn issued his decision on the case this week after an appeals hearing in early June. In a ruling released this week, he wrote that the mobile-home park lease makes tree maintenance the park owner's responsibility.
"Park owners will not be heard to deny liability because (they) failed to act within a reasonably timely and appropriate manner in accordance with the conditions and spirit of mobile park lease agreements," he wrote.
Littlejohn's decision upheld the original ruling awarding one park tenant, Dolores "Dee" Roberts, $3000 plus $50– in attorney's expenses. He awarded a second park tenant Irene Hundley, $1500 plus $20 for attorney costs.
The issue first arose a year ago when Hundley, 71, was taken to small claims court by Lake Bernardo Mobile Home Park's owner, Phil Hohnstein. Hohnstein asked her to pay a $1550 bill for removing an ash tree planted on her lot before she arrived in 1983, she said.
Hundley said Friday that she is relieved with the ruling and wants to put the dispute behind her.
"I am just so very happy because there was no way I could get enough money to pay it" she said of the tree removal. Now, I just want to move and find peace and quiet. This has been a year of nothing but hell and tension and worries."
Hundley's case was heard jointly with a suit filed by Ponderosa Mobile Home Park against Roberts for $750 to remove a palm tree on the land where Roberts' mobile home now sits. Roberts claims the tree caused more than $4,000 damage to her residents requiring her to replace the supports beneath her mobilehome. "I am happy with the decision because somebody had to stand up for all of us mobile home park residents," Roberts said. "At lease I showed them that they can stand up for their rights now."
Mayor Pro Tem June Rady, who attended the hearings and publicly supported the two women, applauded them on Friday.
"I want people to know how proud I am of Irene Hundley and Dee Roberts for having the courage to stand up to the intimidation and harassment that was clearly put upon them by the park owners," she said. "They were absolutely correct in standing for what was fair and right and reasonable."
Both elderly women told the judge in June that they couldn't pay the cost of removing the trees, saying they depend on subsidized housing assistance from the U.S. Department of Housing and Urban Development.
The park owners eventually dropped their claims against the women, (see Page 11, PAIR WINS LAWSUIT)(PAIR WINS LAWSUIT, continued from Page 10)
who then filed cross-complaints for damages the trees caused to their mobile homes. The small claims court judge sided with the tenants on March 27.
The park owners, represented by Orange-based attorney Terry Dowdall, appealed the decision to Littlejohn. Dowdall did not return repeated phone calls this week.
At the appeal hearing, Dowdall told the judge that the tenants want to maintain their own yards and so should be responsible for any damage caused by the trees there.
The tenants attorney is Bernadette Probus, a housing attorney for Legal Aid Society of San Diego. Probus argued during the hearing that her clients were not given a choice in the landscaping around their mobile homes and should not be held responsible for the upkeep.
Steven Nelson, Escondido's deputy city attorney wrote in a brief to the court that the city considers trees to be capital improvement costs and therefore the landlord's responsibility
By admin|2015-05-16T16:10:25+00:00May 13th, 2015|2006, COMO-CAL, THE VOICE|Comments Off on PAIR WINS LAWSUITS OVER TREE UPKEEP – Vista (2006)


text:
November 2, 2021 October 30, 2021 by Lauri D Goldenhersh
Boo humbug!
I used to believe that Halloween isn't for everyone. But as the holiday seems to get bigger every year, it's clear I was wrong. There are hundreds of ways to celebrate this unique holiday, that celebrates very old traditions instead of commemorating a single event or individual.
This year, we see arts organizations running the spooky gamut from concerts that seem to have no creepy connections, to a Russian vespers that brings its own atmosphere, to LA Opera's performance of 'Get Out' — one of cinema's most recent "instant classics". In costume or out, it's a good year for a good scare.
(Make sure YOUR event is on the Lister calendar!)
Rachmaninoff Vespers
Sat, Oct 30 – 7pm, Costa Mesa
Pacific Chorale dives into one of the most unforgettable major choral works in the rep. Join them at Segerstrom Hall for this mammoth work and more, including a world premiere from Tarik O'Regan. The concert is conducted by Robert Istad and features 80 chorus members, marking the first live performance in more than 19 months by Pacific Chorale. Sounds like a great start.
Dana Rouse and friends
Sat, Oct 30 – 7:30pm
California Lutheran Univ, Thousand Oaks
Dana Rouse performs Vaughan Williams' "Ten Blake Songs" for soprano and oboe, as well as "Landscapes," a song cycle for piano, cello, violin and soprano.
Rouse will be joined by pianist Soon Kim, oboe player Lynn Olson and others as they share some rarely heard chamber music pieces.
Opera Meets the Seven Deadly Sins
Thurs, Nov 4 – 8pm, CSU Fullerton
Lust, greed, pride, wrath, gluttony, envy, and sloth take center stage in an eclectic mix of scenes from favorite operas like "Dido and Aeneas" and "The Rake's Progress," and quality outliers such as "Regina" and "The Merry Wives of Windsor," as well as new settings of two of literature's greatest works, "The Scarlet Letter" and "The Grapes of Wrath."
Original published in our Next7 newsletter — Featured events through 11/4/21
Are you getting our public newsletters? Sign up here
Categories Coming soon, Concerts, Newsletter features, Next 7, What's up (Reviews & Previews)
Bulletin markup and hymnal flagging
Fourteen ways to annoy a job lead


in accordance with the current GMP requirements set forth in 21 CFR Part 210 & 211 with its interpretations.
the GMP audits will be noted in the audit report with gap analysis and proposed corrective actions.
Chinese or English version or of both Chinese and English version will be provided.
Remedial actions should be taken to rectify these deficiencies indicated in BBC's GMP audit report.
You can formulate your own remedial action plan or retain BBC as GMP consultant to assist you in the project to improve your GMP compliance status.
in accordance with the current GMP requirements set forth in 21 CFR Part 820 with its interpretations.
the QSR/GMP audits will be noted in the audit report with gap analysis and proposed corrective actions.
to improve your QSR/GMP compliance status.


text:
from __future__ import unicode_literals

from django.contrib import messages
from django.contrib.auth import views
from django.contrib.auth.decorators import login_required
from django.shortcuts import render, redirect
from django.utils.http import urlsafe_base64_decode
from django.views.generic import FormView, DetailView
from django.views.defaults import page_not_found

from admin.common_auth.models import MyUser
from admin.base.forms import GuidForm

@login_required
def home(request):
    context = {}
    return render(request, 'home.html', context)

def password_reset_done(request, **kwargs):
    messages.success(request, 'You have successfully reset your password and activated your admin account. Thank you')
    return redirect('auth:login')

def password_reset_confirm_custom(request, **kwargs):
    response = views.password_reset_confirm(request, **kwargs)
    # i.e. if the user successfully resets their password
    if response.status_code == 302:
        try:
            uid = urlsafe_base64_decode(kwargs['uidb64'])
            user = MyUser.objects.get(pk=uid)
        except (TypeError, ValueError, OverflowError, MyUser.DoesNotExist):
            pass
        else:
            user.confirmed = True
            user.save()
    return response

class GuidFormView(FormView):
    form_class = GuidForm
    template_name = None
    object_type = None

    def __init__(self):
        self.guid = None
        super(GuidFormView, self).__init__()

    def get_context_data(self, **kwargs):
        kwargs.setdefault('view', self)
        kwargs.setdefault('form', self.get_form())
        return kwargs

    def form_valid(self, form):
        self.guid = form.cleaned_data.get('guid').strip()
        return super(GuidFormView, self).form_valid(form)

    @property
    def success_url(self):
        raise NotImplementedError

class GuidView(DetailView):
    def get(self, request, *args, **kwargs):
        try:
            return super(GuidView, self).get(request, *args, **kwargs)
        except AttributeError:
            return page_not_found(
                request,
                AttributeError(
                    '{} with id "{}" not found.'.format(
                        self.context_object_name.title(),
                        kwargs.get('spam_id')
                    )
                )
            )

redpajama_set_name: RedPajamaGithub


Welcome to Picton Accommodation Gateway Motel! Situated at the top of the South Island of New Zealand and gateway to the beautiful Marlborough Sounds, the Gateway Motel is nestled in the heart of Picton.
Your hosts extend a friendly welcome and invite you to experience the genuine Southern hospitality that makes the Gateway Motel a popular location for travellers to relax and enjoy Picton activities.
Our affordable studio includes a spacious queen bed, balcony/terraces furniture, kitchenette (Microwave, Fridge, Toaster, Jug), a bathroom with separate shower area and a vanity. This suite includes good quality bedding and furnishings.
Studio Queen unit has queen size bed. Balcony/terraces furniture, microwave, fridge, toaster and jug, a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings.
Studio unit has queen size bed and single bed. Balcony/terraces furniture, microwave, fridge, toaster and jug, a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings. Cot Hire available.
Studio deluxe family unit has queen size bed and single bed. Balcony/terraces furniture, kitchen (Microwave, Fridge), a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings.
This exceptional suite includes a spacious master bedroom (Queen sized bed and two singles beds) balcony/terraces furniture, full kitchen (Oven, Microwave, Fridge), a bathroom with separate shower area and a vanity. This suite includes high quality bedding and furnishings.
The one bedroom apartment consist of two rooms, a queen size bed in the main area with two single beds in a separate bedroom. Balcony/terraces furniture, kitchenette (Stovetop, Microwave, Fridge), a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings. Cot Hire available.
Two bedroom family unit with separate lounge, master bedroom has queen size bed, second bedroom has two single beds, lounge also has one single bed. Balcony/terraces furniture, kitchenette (Stovetop, Microwave, Fridge), a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings.
Two bedroom deluxe family unit with separate lounge, master bedroom has queen size bed, second bedroom has a double and single bed. Balcony/terraces furniture, full kitchen (Oven, Microwave, Fridge), a bathroom with shower area and a vanity. This suite includes high quality bedding and furnishings.
Modern and Luxurious Fully Self-Contained 3 Bedroom Waterfront Apartments with Views of Picton Waterfront & Harbour. Walking Distance to Ferry, Train Station, Cafes, Marina & Shops.Free unlimited wifi.
PLEASE NOTE THIS APARTMENT IS OFF-SITE.
Your reservation will be accepted and guaranteed once we have received your valid credit card number, cardholders name and card expiry date as supplied at the time the reservation is made. We accept all major Credit Cards. New Zealand banking laws require that all credit card transactions be charged in New Zealand currency.
Unless advised otherwise, we require 48 hours notice of cancellation that applies to the full term of your reservation. If you have to cancel at short notice, or when guests fail to arrive, every endeavor will be made to re-let your booking, however if we are unsuccessful then you will be responsible for the balance owing.


text:
''Nota: Para as outras empresas com esse nome, veja Rover Company e Rover (marca).

The Rover Group plc era um conglomerado britânico de fabricação de veículos conhecido como "BL plc" até 1986 (ex-British Leyland), que era uma empresa estatal desde 1975. Inicialmente incluía o setor de automóveis do Grupo Austin Rover (composto pelas marcas Austin, Rover, Mini e MG), Grupo Land Rover, vans Freight Rover e Leyland Trucks. O Grupo Rover também possuía as marcas registradas inativas das muitas empresas que se fundiram à BL e seus predecessores, como Triumph, Morris, Wolseley, Riley e Alvis.

O Grupo Rover foi controlado pela British Aerospace (BAe) de 1988 a 1994, quando a BAe vendeu o restante do setor de automóveis para a empresa alemã BMW. O grupo foi dividido em 2000, quando a Ford adquiriu a divisão Land Rover, com as marcas Rover e MG continuando com o muito menor Grupo MG Rover até 2005. A propriedade das marcas originais do Grupo Rover estão atualmente divididas entre BMW (Alemanha), SAIC (China) e Tata Motors (Índia), esta última é proprietária da marca Rover, com sua subsidiária, a Jaguar Land Rover, detentora de grande parte dos ativos da histórica empresa Rover.

Ligações externas
 Why did BMW buy Rover? Consultado em julho de 2019.
 Catalogue of the Rover Group archives, realizada no Centro de Registros Modernos da Universidade de Warwick.

Fabricantes de automóveis extintas do Reino Unido
Empresas ex-listadas na Bolsa de Valores de Londres
Rover Company

redpajama_set_name: RedPajamaWikipedia


It's time again for one of our favorite campus events: Pet Therapy! Our next Pet Therapy event is going to be held on Monday, November 19th 6 – 7:30 pm, outside the library media viewing rooms. This event is, as always, provided by our friends at Pet Partners of Central New York. Please stop by and relax with our furry friends!
The Le Moyne College Noreen Reale Falcone Library is now on social media! You can now follow us on Facebook, Instagram, and Twitter to stay up-to-date on all of our events, news, and updates!


text:
Mastercard enters 'buy now, pay later' battle with new installment loan program
By Renae R. Scott Last updated Apr 18, 2022
The MasterCard logo on a smartphone disposed in Saint Thomas, Virgin Islands.
Gabby Jones | Bloomberg | Getty Images
Mastercard is entering the competitive installment loan space by allowing banks and start-ups to scale up their own "buy now, pay later" offers.
The payments giant on Tuesday announced a new program called "Mastercard Payments" for the US, Australian and UK markets, which will go live in the first quarter of next year. The increasingly popular style of loan allows buyers to split their purchases through monthly payments, often without interest.
Mastercard does not lend directly to customers. Its network acts as an intermediary in the process of paying credit and debit cards. In this case, it will allow banks and fintechs to "connect" to the Mastercard program and offer loans directly.
US consumer bank Barclays, SoFi, Synchrony and Marqeta are among those who have said they plan to use Mastercard to roll out installment loans.
"Consumers are showing great interest in this ability to buy now, pay later," Craig Vosburg, chief product officer at Mastercard, said in a telephone interview. "It is using the power of the Mastercard network and franchise to market it on a large scale. "
The so-called BNPL loans increase sales by 45% on average, and reduce "cart abandonment" by 35%, according to Mastercard. Vosburg said marketers see these types of loans as a way to generate more sales. Customers, on the other hand, tend to look to these loans as cheaper and more convenient alternatives to traditional revolving credit.
Space has become a battleground for banks and fintechs.
Jack Dorsey's Square announced a $ 29 billion deal in August to buy Australian company AfterPay as a foray into space. Affirm, one of the oldest and best-known companies in the industry, recently partnered with Amazon for a buy-now and check-out option on the ecommerce site.
PayPal, Klarna, Mastercard and Fiserv, American Express, Citi, and JP Morgan Chase all offer similar loan products. Apple plans to launch installment loans as part of a partnership with Goldman Sachs, Bloomberg reported. The rival of Mastercard Visa is development a similar product.
Claiming CEO Max Levchin is among those who have argued that the installment loan could be a threat to traditional card players, like Mastercard and Visa, by cutting revolving credit. But Vosburg said it was "additive". Most of the payments made to fund loans tend to be a Mastercard credit transaction, in which the company charges a small fee.
"We are seeing a high prevalence, in our program and others, of people choosing Debit Mastercard as a means of repayment," Vosburg said. "This is in line with our mission to provide choice for both consumers in terms of payment method and merchants in terms of payment method. "
The plans differ in terms of interest payments, although many are initially interest-free. Mastercard said it is up to the lender to decide the rate and whether or not to allow credit cards to be used to fund installment loans.
Others cautioned against the risk of additional credit and what is called "debt stacking" – or using traditional forms of credit to fund these installment loans. Some late payment offers are also not reported to the credit bureaus. The companies offering these loans say they are able to use data to assess creditworthiness better than a traditional FICO score.
"Lenders don't want to extend loans that can't be repaid, and we don't want to see lenders doing that – so we're actively working to improve the visibility of information on consumers' ability to repay a loan," he said. declared Vosbourg.
Subscribe to CNBC PRO for exclusive news and analysis, and live business day programming from around the world.
Lakeland Bancorp, Inc. (NASDAQ:LBAI) is expected to report earnings of $0.33 per share
Brokerages expect Investor Holding Co. (NASDAQ:ISTR) to post $0.55 EPS
America's largest banks are making major changes to overdrafts that will help consumers
Understanding Your Credit Score: What Makes Up Your FICO Score
Minneapolis partners with media to disseminate information on COVID vaccines to communities of color – WCCO
Open banking, BNPL and banking transformation
Veterinary Telemedicine Company Dutch launches pet insurance in partnership with Pets…


text:
Wiesław Czaja (born 12 April 1952) is a Polish former volleyball player and coach, a member of the Poland national team from 1974 to 1980, and the 1974 World Champion. He competed in the 1980 Summer Olympics held in Moscow, finishing in 4th place with his national team.

Honours

As a coach
 Youth national team
 2013  European Youth Olympic Festival

External links

 Coach/Player profile at Volleybox.net

1952 births
Living people
People from Czechowice-Dziedzice
Polish men's volleyball players
Polish volleyball coaches
Olympic volleyball players of Poland
Volleyball players at the 1980 Summer Olympics
AZS Częstochowa players
Skra Bełchatów coaches


Ready to step up your involvement in youth sports and make a difference in your community? Consider becoming an At-Large member of the Arlington Soccer Association Board. In April, the Arlington Soccer Board will accept applications for three At-Large Board Member vacancies. For more information on the Board and the application process, please see our Q&As.


Co-Editor, Special Issue of the Journal of Experimental Analysis of Behavior, November, Vol 84(3), 2005.
Young, B.W., Sengelaub, D.R. and Steinmetz, J.E. (2010). MK-801 administration during neonatal ethanol withdrawal attenuates interpositus cell loss and juvenile eyeblink conditioning deficits. Alcohol, 44(4), 359-369.
Bolbecker, A.R., Steinmetz, A.B., Mehta, C. S., Forsyth, J. K., Klaunig, M. J., Lazar, E. K., Steinmetz, J.E., O'Donnell, B. F. and Hetrick, W.P. (2011). Exploration of cerebellar-dependent associative learning in schizophrenia: Effects of varying and shifting interstimulus interval on eyeblink conditioning performance. Behavioral Neuroscience,125(5), 687-698.
Steinmetz, A.B., Bolbecker, A.R., Skosnik, P.D., Edwards, C.R. Steinmetz, J.E. and Hetrick, W.P. (2011). Evaluation of Bidirectional interstimulus interval (ISI) shift in auditory delay eyeblink conditioning in healthy humans. Learning and Behavior, 39(4), 358 -370.
Forsyth, J.K., Bolbecker, A.R., Mehta, C.S., Klaunig, M.J., Steinmetz, J.E., O'Donnell, B.F. and Hetrick, W.P. (2012). Cerebellar - dependent eyeblink conditioning deficits in schizophrenia spectrum disorders. Schizophrenia Bulletin, 38(4), 751-759.
Lindquist, D.H., Sokoloff, G., Milner, E., and Steinmetz, J.E. (2013). Neonatal ethanol exposure results in dose - dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats, Alcohol, 47(6), 447-457.
Lindquist, D.H. and Steinmetz, J.E. (2008). Classical Conditioning. In: W.A. Darity, Jr. (Ed.), International Encyclopedia of the Social Sciences, 2nd edition, pp. 572-575, Detroit: Macmillan Reference, USA.
Steinmetz, J. E. and Lindquist, D. H. (2009). Neuronal basis of learning. In: G.G. Berntson and J.T. Cacioppo (Eds.), Handbook of Neuroscience for the Behavioral Sciences, Vol 1, New York: John Wiley and Sons.
Steinmetz, J.E. (2010). Neural Basis of Classical Conditioning. In G Koob, M. Le Moal and R.F. Thompson and (Eds.), Encyclopedia of Behavioral Neuroscience, London: Elsevier.
Lindquist, D. H., Steinmetz, J.E., and Thompson, R.F. (2012). Cerebellum and Eyeblink Conditioning. In: M. Manto, D. L. Gruol, J. D. Schmahmann, N. Koibuchi and F. Rossi (Eds.), Handbook of the Cerebellum and Cerebellar Disorders, pp. 1175 - 1190, New York: Springer Science.
Kim, J., Steinmetz, J.E., and Thompson, R.F. (2013). Biological models of associative learning. In: R.J. Nelson and S. Mizumori (Eds.), Handbook of Psychology, Volume 3. Biological Psychology (Chapter 19), pp. 509 - 550, New York: Wiley.
Steinmetz, J.E. (2007). The importance of external grant support for a public college of arts and science. Proceedings of the 2007 Summer Merrill Center Conference, MASC Report No. 111, 28-31.
Steinmetz, J.E. (2013). University decision-making using data analytics. Proceedings of the 2013 Summer Merrill Research Conference.
Steinmetz, J.E. (2014). Remembering Richard F. Thompson: September 6, 1930 – September 16, 2014. Observer, 28(1), 29 - 31.
Invited Presentation, Good Reason for Doing Something, The 31st Annual Gathering of the National Council of Arts Administrators, Columbus, OH, November, 2012.
Commencement Speaker, Decisions and Choices, Central Michigan University Fall Commencement, December, 2012.
Presidential Symposium, Learning and Memory: Molecules to Mind, (with T. Abel, M. Fanselow, E.F. Loftus, and E.A. Phelps), 25th Annual Meeting of the Association for Psychology Science, Washington DC, May 2013.
Key Note Address, University Decision - Making and Data Analytics, 2013 Meeting of the Merrill Advanced Study Center, Nebraska City, Nebraska, July 2013.
Key Note Address, Leading in a New World Order: The View from Above, 2014 Meeting of the Council of Graduate Departments of Psychology, Savannah, GA, February 2014.


Welcome to watch Brumbies Vs Waratahs 2018 Super Rugby week 19 Hd live streaming on your smart devices around the earth. The Waratahs Vs Brumbies rugby match will be beginning at the time 19:45 Local / 9:45 GMT and will play at the Allianz Stadium, Sydney.
Here you can see the entire Super Rugby 2018 competition live stream, all you need to get a premium subscription and enjoy all rugby matches live online in high definition video and sound quality on your PC, laptop, iPad, iPhone, Tablet, Mac and other smart devices internationally.