INTRODUCTION
============

Neuropsychological-anatomical correlations are important for clinical practice. They are not only important for understanding a patient\'s current clinical symptoms, but also important for predicting the progression of symptoms. In this regard, researchers have tried to find out whether specific forms of cognitive deficits are directly correlated with certain brain regions using several methods including injury-lesion and functional neuroimaging studies. Initially, case studies of patients with strokes or head injuries have shown brain-behavior relationships. Functional neuroimaging studies have also been performed to determine the function of a specific brain region.

With the advent of neuroimaging techniques, it is possible to detect subtle changes of cortical structures in neurodegenerative diseases. Increasing evidence showed that various kinds of cognitive dysfunctions were often related to cortical atrophy in neurodegenerative diseases including Alzheimer\'s disease (AD).[@B1][@B2][@B3][@B4] A previous study from our group investigated the correlation between neuropsychological tests of the Seoul Neuropsychological Screening Battery (SNSB) and the cortical thickness in a number of patients with AD or amnestic mild cognitive impairment (aMCI).[@B4] Results showed that poor performances in most neuropsychological tests were correlated to cortical thinning in specific brain areas. Thus, cortical thinning was useful for understanding neural correlates of cognitive deficits.

The diagnosis of AD and aMCI patients in the prior study only relied on clinical consequences including symptoms and signs. However, the importance of biomarkers for AD has been on the rise because the National Institute on Aging and Alzheimer\'s Association has shifted the definition of AD in living people from a syndrome to a biological construct.[@B5] According to this paradigm shift, Alzheimer\'s pathologic change without clinical syndrome and AD are not regarded as separate entities, but earlier and later phases of "Alzheimer\'s continuum" including preclinical AD, mild cognitive impairment (MCI) due to AD and AD dementia. However, neural correlates targeting all participants with Alzheimer\'s pathology have not been reported yet. Thus, it is necessary to investigate neural correlates of Alzheimer\'s continuum including preclinical AD.

The SNSB was modified and complemented to produce the SNSB-II in 2012.[@B6] The norms by which raw scores could be converted to z-scores were changed and new forms of assessment were added to reflect the latest trends. The Flynn effect, which is the general trend of increased intelligence quotients (IQs) over time, is estimated to contribute to an increase of 0.3 IQ points per year.[@B7] During periodic revision and restandardization of the Wechsler intelligence scales, subjects in validation samples who were administered by both older and newer versions of the same test consistently obtained higher IQ scores on the older version.[@B8][@B9][@B10] This meant that norms for the newer tests were more stringent. This phenomenon may also apply to restandardization of the SNSB-II.

The present study aimed to explore neuropsychological test-specific neuroanatomical correlates representing the relationship between cortical atrophy measured by cortical thickness and performance in specific neuropsychological tests measured by SNSB-II in a large sample of subjects with Alzheimer\'s continuum. This study also investigated whether there were discrepancies between neuroanatomical correlates of z-scores which was converted from raw scores based on the criteria in the SNSB-I and those of z-scores using the criteria in the SNSB-II. We hypothesized that statistic maps of SNSB-II z-scores were broader than those of SNSB-I z-scores.

METHODS
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Participants
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A total of 249 participants with Alzheimer\'s continuum (125 participants with AD dementia, 103 participants with MCI due to AD, and 21 participants with preclinical AD) were collected from the memory disorder clinic in the department of neurology at Samsung Medical Center in Seoul, Korea between September 2013 and March 2018. Each participant received neuropsychological battery, high-resolution T1-weighted magnetic resonance imaging (MRI) scan, and ^18^F-flutemetamol positron emission tomography (PET) to assess amyloid-β (Aβ) deposition. The time interval between assessments was less than 6 months. According to the National Institute on Aging-Alzheimer\'s Association criteria,[@B11][@B12][@B13] Aβ (+) cognitive normal or subjective memory concerns, Aβ (+) MCI, and Aβ (+) clinically diagnosed AD type dementia were defined as preclinical AD, MCI due to AD, and AD dementia, respectively. We excluded secondary causes of cognitive impairment by laboratory tests, including complete blood count, blood chemistry, vitamin B12/folate, syphilis serology, and thyroid function tests. All participants had no significant whiter matter hyperintensities (cap or band \<5 mm and the longest diameter of deep white matter lesion \<10 mm), cerebral infarctions, intracranial hemorrhages, brain tumors, hydrocephalus, or other structure lesions.

Our study protocol was approved by the Institutional Review Board (IRB) of Samsung Medical Center (IRB file No. 2013-07-073). All participants provided informed consent for research according to the guidelines outlined in the Declaration of Helsinki.

Neuropsychological tests
------------------------

SNSB-II, a neuropsychological battery including standardized and validated tests of a variety of cognitive functions,[@B6] was used to access all participants, although a small number of participants could not complete all these tests. The SNSB-II evaluates many cognitive factors, including verbal and visual memory, visuoconstructive function, language, praxis, components of Gerstmann syndrome (acalculia, agraphia, right/left disorientation, finger agnosia), and frontal/executive functions. We used tests that provided numeric scores, such as digit span (forward and backward), the Korean version of the Boston Naming Test (K-BNT), the Seoul Verbal Learning Test (SVLT) (immediate and 20-minutes delayed recall and recognition), the Rey-Osterrieth Complex Figure Test (RCFT) (copying, immediate and 20-minutes delayed recall and recognition), the Clock Drawing Test (CDT), the Controlled Oral Word Association Test (COWAT), the Stroop test, the Digit Symbol Coding (DSC), and part B of the Trail Making Test (TMT-B) for our study. Results with numeric continuous values were converted to z-scores using age, sex, and education criteria presented in the SNSB-II except for the DSC. We obtained 3 types of scores including raw scores, SNSB-II z-scores, and SNSB-I z-scores. SNSB-II z-scores represented standardized z-scores corrected by norms presented in the SNSB-II. SNSB-I z-score meant standardized z-scores based on norms of the SNSB-I except for the CDT, the DSC, and the TMT-B.

Acquisition of 3-dimensional MRI images
---------------------------------------

Three-dimensional T1 Turbo Field Echo MRI images for 249 participants (125 participants with AD dementia, 103 participants with MCI due to AD, and 21 participants with preclinical AD) were acquired using a 3.0T MRI scanner (Philips 3.0T Achieva; Philips Medical Systems, Best, the Nederland) with the following imaging parameters: sagittal slice thickness, 1.0 mm with 50% overlap; no gap; repetition time of 9.9 ms; echo time of 4.6 ms; flip angle of 8°; and matrix size of 240×240 pixels reconstructed to 480×480 over a field view of 240 mm.

MRI data processing for cortical thickness measurements
-------------------------------------------------------

Images were processed using the CIVET anatomical pipeline.[@B14] Native MRI images were registered to the Montreal Neurological Institute -152 template by a linear transformation[@B15] and corrected for intensity non-uniformities using the N3 algorithm.[@B16] Registered and corrected images were divided into white matter, gray matter, cerebrospinal fluid, and background. Using the Constrained Laplacian-based Automated Segmentation with Proximities algorithm,[@B17][@B18] surfaces of inner and outer cortices were extracted automatically. Inner and outer surfaces had the same numbers of vertices. There were close correspondences between counterpart vertices of inner and outer cortical surfaces. Cortical thickness defined as the Euclidean distance between linked vertices of inner and outer surfaces[@B19] was not calculated in Talairach spaces, but in native brain spaces due to the limit to linear stereotaxic normalization. As expected, there was a significant positive correlation between cortical thickness and intracranial volume (ICV) in native space.[@B20] Controlling for ICV reflecting brain size effect was necessary to compare cortical thickness among participants. In the previous study,[@B20] our group proposed that the measurement of native space cortical thickness followed by analyses that include brain size as a covariate is an efficient method to explain the relationship between cortical thickness and brain size in depth. ICV was defined as the total volume of gray matter, white matter, and cerebrospinal fluid. It was calculated by measuring total volumes of voxels within the brain mask made by Functional Magnetic Resonance Imaging of the Brain Software Library using BET algorithm.[@B21] As we extracted cortical surface models from MRI volumes transformed into stereotaxic space, cortical thickness was measured in the native space by applying an inverse transformation matrix to cortical surfaces and reconstructing them in native space.[@B22]

We applied surface-based 2-dimensional registration with a sphere-to-sphere warping algorithm and normalized cortical thicknesses spatially to compare thicknesses of corresponding regions among subjects. We used an improved surface registration algorithm and an unbiased iterative group template showing enhanced anatomic detail[@B23] to transform thickness information for vertices into an unbiased iterative group template. Surface-based diffusion smoothing with a full-width at half-maximum of 20 mm was used to blur each map of cortical thickness to increase signal-to-noise ratio and statistical power.[@B19][@B22][@B24]

Asymmetric index (AI)
---------------------

To measure an asymmetric degrees of neuroanatomical correlates for neuropsychological tests, we obtained an AI which was calculated with the following formula: (R−L/R+L), where R was the number of vertices with significant correlations in the right hemisphere and L was the number of vertices with significant correlations in the left hemisphere.[@B4] After obtaining the AI, we divided the extent of asymmetry into 3 groups according to absolute value of the AI. \|AI\|\<0.1, 0.1≤\|AI\|\<0.5, and \|AI\|≥0.5 were classified as no hemispheric dominance, weak hemispheric dominance, and strong hemispheric dominance, respectively.

Statistical analyses
--------------------

Chi-square test and analysis of variance with Bonferroni post-hoc tests were used to compare demographic and clinical characteristics of groups. For cortical thickness analyses of MRI data from Alzheimer\'s continuum patients, a MATLAB-based toolbox available free online at the University of Chicago website (<http://galton.uchicago.edu/faculty/InMemoriam/worsley/research/surfstat/>) was used. We entered score of each neuropsychological test as a predictor and vertex-by-vertex cortical thickness as an outcome to analyze the relationship between cortical thickness and neuropsychological performance in the surface model. A linear regression was then performed after controlling for sex, education years, Mini Mental State Examination (MMSE) score, and ICV as covariates. Statistical maps were thresholded using the random field theory at *p*\<0.05. SPSS version 25.0 (SPSS Inc., Chicago, IL, USA) was used and 2-sided *p*-value\<0.05 was regarded as significant in our study to analyze statistical data.

RESULTS
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Clinical characteristics of our participants
--------------------------------------------

Demographic and clinical data of the participants are presented in [Table 1](#T1){ref-type="table"}. There were no significant differences in age, sex, or educational level among groups.

###### Demographic variables, MMSE scores of normal cognition, aMCI, and AD groups

![](dnd-18-77-i001)

  Variable       Preclinical AD (n=21)   MCI due to AD (n=103)   AD dementia (n=125)   Total      *p*-value
  -------------- ----------------------- ----------------------- --------------------- ---------- -----------
  Age (yr)       69.5±6.9                70.4±6.4                68.3±7.6              69.3±7.1   0.092
  Sex (M:F)      10:11                   44:59                   52:73                 106:143    0.875
  Education      10.2±4.9                11.5±4.5                11.8±4.1              11.5±4.3   0.310
  MMSE (score)   27.9±1.6                25.4±3.2                19.0±6.1              22.4±5.9   \<0.001

Values are presented as mean±standard deviation. 'n' represents number of patients whose data were available for analysis. The *p*-value was obtained by analysis of variance model and χ^2^ test.

AD: Alzheimer\'s disease, MCI: mild cognitive impairment, aMCI: amnestic mild cognitive impairment, MMSE: Mini Mental State Examination.

Correlation between neuropsychological tests and cortical thickness
-------------------------------------------------------------------

[Table 2](#T2){ref-type="table"} presents results of neuropsychological tests for participants with AD dementia, participants with MCI due to AD, and participants with preclinical AD.

###### Results of neuropsychological tests for AD dementia group, MCI due to AD group, normal preclinical AD group, and total participants

![](dnd-18-77-i002)

  Neuropsychological test      AD dementia                  MCI due to AD   Preclinical AD   Total
  ---------------------------- ---------------------------- --------------- ---------------- ----------- ----- -------------
  Attention
                               Forward digit span           5.2±1.6         6.0±1.4          6.1±1.8     249   5.6±1.6
                               Backward digit span          3.0±1.4         3.8±1.1          4.1±1.5     246   3.4±1.3
  Language
                               K-BNT                        34.0±13.5       41.9±10.6        48.5±6.3    238   38.5±12.8
  Visuospatial function
                               RCFT: copying                19.8±12.0       29.1±7.4         31.8±6.0    245   24.7±11.0
                               CDT                          2.0±0.9         2.5±0.8          2.8±0.5     193   2.3±0.9
  Memory
                               SVLT: immediate recall       10.9±5.3        14.4±4.2         20.9±5.0    249   13.2±5.6
                               SVLT: delayed recall         0.7±1.3         1.6±2.1          7.2±2.1     249   1.6±2.5
                               SVLT: recognition            15.5±2.9        18.1±2.6         21.2±1.5    249   17.1±3.2
                               RCFT: immediate recall       3.0±3.4         6.2±4.9          14.4±6.2    244   5.3±5.4
                               RCFT: delayed recall         1.8±3.0         5.5±4.9          14.0±5.9    244   4.4±5.4
                               RCFT: recognition            15.4±2.8        17.8±2.5         19.4±2.8    244   16.7±3.0
  Frontal/executive function
                               COWAT: animal                8.4±4.5         12.0±4.5         14.4±5.1    249   10.4±5.0
                               COWAT: supermarket           8.0±5.1         12.5±5.5         17.0±6.1    234   10.6±6.1
                               COWAT: phonemic              15.0±10.9       22.1±10.9        24.2±13.5   220   18.8±11.7
                               Stroop test: color reading   36.7±26.8       63.9±29.0        82.2±25.3   229   52.5±31.8
                               TMT-B                        188.6±107.1     92.5±86.9        66.9±39.0   184   134.2±106.4
                               DSC                          30.6±17.1       63.9±29.0        82.2±25.3   183   37.2±17.9

Number represents number of patients whose data were available for analysis.

AD: Alzheimer\'s disease, MCI: mild cognitive impairment, SD: standard deviation, K-BNT: Korean version of the Boston Naming Test, RCFT: Rey-Osterrieth Complex Figure Test, CDT: Clock Drawing Test, SVLT: Seoul Verbal Learning Test, COWAT: Controlled Oral Word Association Test, TMT-B: part B of the Trail Making Test, DSC: Digit Symbol Coding.

The statistical map showed that cortical thinnings in specific brain regions were associated with raw scores of all neuropsychological tests except for forward digit span, recognition in the RCFT, and the TMT-B ([Fig. 1](#F1){ref-type="fig"} and [Table 3](#T3){ref-type="table"}). Specifically, scores in the backward digit span test which reflected attention and working memory were positively associated with cortical thicknesses in the left middle frontal and supramarginal gyri. Scores in the Boston Naming Test (BNT) reflecting language function were positively associated with cortical thicknesses in the left inferior temporal and fusiform gyri. Scores in the immediate recall in the SVLT which was included in the memory domain were positively associated with cortical thicknesses in the bilateral superior & middle frontal gyri and middle & inferior temporal gyri. Scores in delayed recall and recognition of the SVLT were positively associated with cortical thicknesses in bilateral medial temporal regions. Scores in the copying test of the RCFT composing visuospatial domain were positively correlated with cortical thicknesses in widespread regions including bilateral parieto-occipital area and fusiform & lingual gyri. Scores in the immediate recall in the RCFT which comprised the memory domain were positively correlated with cortical thicknesses in the right medial temporal region, superior parietal lobule, precuneus, and left lingual gyrus. Scores in the delayed recall of the RCFT were positively correlated with cortical thicknesses in bilateral medial temporal regions and right superior parietal lobule. Scores in the semantic component of the COWAT (animal) were positively correlated with cortical thicknesses in the left medial frontal gyrus, middle & inferior temporal gyri, superior parietal lobule angular gyrus, and precuneus. Score in the semantic component of the COWAT (supermarket) were positively correlated with cortical thicknesses in the bilateral superior& middle & medial frontal gyri, middle& inferior temporal gyri, and left lateral parietal lobule. Scores in the phonemic component of the COWAT were positively correlated with cortical thicknesses of the right superior parietal lobule. Scores in the color reading portion of the Stroop test were positively associated with cortical thicknesses in the right prefrontal, right superior & middle & medial frontal gyri, left premotor cortex, and bilateral lateral parieto-temporal areas.

![Correlation maps demonstrating associations between cortical thickness and neuropsychological tests in patients with Alzheimer\'s continuum (AI \>0 means right-sided correlated areas \> left-sided correlated areas, and vice versa for AI \<0).\
AI: asymmetric index, BNT: Boston Naming Test, SVLT: Seoul Verbal Learning Test, RCFT: Rey-Osterrieth Complex Figure Test, COWAT: Controlled Oral Word Association Test, DSC: Digit Symbol Coding, CDT: Clock Drawing Test.](dnd-18-77-g001){#F1}

###### Correlations among neuropsychological tests, cortical thickness, and hemispheric dominance

![](dnd-18-77-i003)

  Neuropsychological test                                                         Correlation areas                                                    Hemispheric dominance
  ------------------------------------------------------------------------------- -------------------------------------------------------------------- -----------------------
  Digit span backward                                                             Left: frontal (mid, inf), parietal (inf)                             Left strong dominance
  Right: none
  BNT                                                                             Left: temporal (mid, inf)                                            Left strong dominance
  Right: none
  SVLT immediate recall                                                           Left: frontal (sup, mid, med), temporal (mid, inf)                   Left weak dominance
  Right: frontal (sup, mid, med), temporal (mid, inf)
  SVLT delayed recall                                                             Left: temporal (med, inf)                                            Left weak dominance
  Right: temporal (med)
  SVLT recognition                                                                Left: temporal (med)                                                 Left weak dominance
  Right: temporal (med)
  RCFT copying                                                                    Left: parietal (sup, inf), temporal (post), occipital                Right weak dominance
  Right: frontal (sup, mid), parietal (sup, inf) temporal (mid, inf), occipital
  RCFT immediate recall                                                           Left: temporal (inf)                                                 Right weak dominance
  Right: parietal (sup, med), temporal (med), occipital
  RCFT delayed recall                                                             Left: temporal (inf, med)                                            Right weak dominance
  Right: parietal (sup, med), temporal (inf, med)
  COWAT animal                                                                    Left: frontal (med, inf), parietal (sup, inf), temporal (mid, inf)   Left strong dominance
  Right: none
  COWAT supermarket items                                                         Left: frontal (sup, med), parietal (sup, inf), temporal (mid, inf)   Left weak dominance
  Right: frontal (sup, mid)
  COWAT phonemic fluency                                                          Left: parietal (inf)                                                 Right weak dominance
  Right: parietal (sup)
  Stroop test color reading                                                       Left: frontal (sup, mid), parietal (inf), temporal (mid, inf)        None
  Right: frontal (sup, mid, med), parietal (sup, inf), temporal (inf)
  DSC                                                                             Left: frontal (mid), parietal (inf), temporal (inf)                  None
  Right: frontal (mid), parietal (sup, inf), temporal (inf), occipital
  CDT                                                                             Left: parietal (sup), temporal (inf), occipital                      Right weak dominance
  Right: parietal (sup, med), occipital

BNT: Boston Naming Test, SVLT: Seoul Verbal Learning Test, RCFT: Rey-Osterrieth Complex Figure Test, COWAT: Controlled Oral Word Association Test, DSC: Digit Symbol Coding, CDT: Clock Drawing Test.

Hemispheric dominance of cortical thickness related to neuropsychological results
---------------------------------------------------------------------------------

We also investigated hemispheric dominance of neural correlates by using AI ([Table 3](#T3){ref-type="table"}). Neural correlates for backward digit span test, the BNT, and semantic component of the COWAT (animal) showed strong left hemispheric dominance. Neural correlates for all components of the SVLT and semantic component of the COWAT (supermarket) had weak left hemispheric dominance. In contrast, neural correlates for phonemic component of the COWAT showed strong right hemispheric dominance, and neural correlates for copying test of the RCFT, immediate and delayed recall of the RCFT, and the CDT showed weak right hemispheric dominance.

Comparison with 2 different statistical maps of z-scores
--------------------------------------------------------

Results of our study showed differences between statistical maps of SNSB-II z-scores and statistical maps of SNSB-I z-scores except for forward digit span and recognition in the SVLT and RCFT ([Fig. 2](#F2){ref-type="fig"}). Statistical maps of SNSB-II z-scores were wider than those of SNSB-I z-scores in backward digit span test, the BNT, immediate recall and delayed recall of the SVLT, immediate recall, delayed recall and recognition of the RCFT, and semantic component of the COWAT (animal). Opposite results were shown in semantic component of the COWAT (supermarket) and phonemic component of the COWAT. Two kinds of statistic maps had non-overlapping areas in copying test of the RCFT and color reading portion of the Stroop test. Non-overlapping areas in copying test of the RCFT were left middle frontal gyrus (which only correlated with the SNSB-I z-score) and right posterior cingulate gyrus (which only correlated with the SNSB-II z-score). Non-overlapping areas in the color reading portion of the Stroop test were left middle frontal gyrus (which was only associated with the SNSB-I z-score), bilateral superior parietal lobule, occipital pole, left precuneus, right superior & inferior temporal gyri, and parahippocampal gyrus, all of which were only associated with the SNSB-II z-score.

![Difference in cortical atrophy pattern between correlation maps with SNSB-II z-score and those with SNSB-I z-score.\
BNT: Boston Naming Test, SVLT: Seoul Verbal Learning Test, RCFT: Rey-Osterrieth Complex Figure Test, COWAT: Controlled Oral Word Association Test, SNSB: Seoul Neuropsychological Screening Battery, SMA: supplementary motor area.](dnd-18-77-g002){#F2}

DISCUSSION
==========

The present study investigated relationships between cortical thickness and neuropsychological results in Alzheimer\'s continuum. We found that most of neuropsychological tests were associated with specific cortical regions. Especially, we obtained AI to demonstrate laterality representing impaired performances of certain neuropsychological tests was more likely to be associated with dysfunction in one hemisphere than the other. Finally, comparison with 2 different statistical maps of z-scores showed the degree of discrepancy between neural correlates of z-scores converted from raw scores based on the criteria in the SNSB-I and those of z-scores using the criteria in the SNSB-II.

Deficit in the backward digit span was correlated with decreased cortical thickness in the left middle frontal gyri and supramarginal gyrus. Considering that to perform backward digit span, temporarily store of digits which were presented was needed additionally and this process required working memory for temporal order, it would be reasonable to expect that backward digit span might be related to regions responsible for working memory. Convergent evidence from lesions[@B25][@B26][@B27] and functional MRI (fMRI)[@B28][@B29][@B30][@B31][@B32] have suggested that prefrontal areas could play a critical role in working memory. A few fMRI studies have also shown that activation posterior parietal cortex is increased during a temporal order working memory task.[@B33][@B34] In fact, fMRI studies have revealed that the backward digit span test is associated with activation in the right and left dorsolateral prefrontal cortex, inferior parietal lobule, Broca\'s area, and anterior cingulate gyrus.[@B35][@B36][@B37]

In the present study, poor performances in BNT were associated with decreased cortical thicknesses in the left inferior temporal and fusiform gyri. BNT reflects semantic representation which lies in the inferior temporal lobe[@B38] or the left temporal and parietal cortices.[@B39] In fact, previous neuroimaging studies have shown that bad performances in BNT are linked to cortical thinning in the left middle temporal, superior temporal gyri, inferior parietal cortex,[@B40][@B41] and hypometabolism in the left middle temporal and fusiform.

We found that the low performance of RCFT was associated with cortical atrophy in extensive brain regions including bilateral lateral parietal lobule, precuneus, posterior cingulate gyrus, fusiform gyrus, lingual gyrus, occipital lobe, and left prefrontal cortex in the present study. Previous studies have shown that poor performance in the RCFT is related to lesions in the right frontal lobe, superior temporal gyrus, lateral parietal lobule, and middle occipital gyrus.[@B42] The RCFT copying test represents visuo-perceptive and visuo-constructive functions related to parietal and frontal regions, respectively. CDT also represents visuo-perceptive and visuo-constructive functions like the RCFT copying test. However, its deficits were related to decreased cortical thickness in the parietal region. In fact, a previous study has demonstrated that CDT performance is related to temporo-parietal regions.[@B43][@B44] It might be related to the fact that recent studies have shown that visuo-constructive task is mainly related to parieto-temporal regions.[@B3][@B45] Alternatively, the RCFT might be more complex than the CDT. Thus, it necessitates executive function more than the CDT.

Poor performance of the SVLT immediate recall was related to cortical thinning in the frontal region as well as lateral temporal region while poor performances of the SVLT delayed recall and recognition were associated with cortical thinning primarily in the medial temporal areas. The immediate recall task of the SVLT was used to access verbal learning ability while the delayed recall task of the SVLT was used to evaluate ability of memory consolidation. Verbal learning ability was correlated with medial frontal area, prefrontal area, and lateral temporal area in prior studies.[@B46][@B47][@B48][@B49] The essential role of medial temporal lobe structures for the consolidation of new information has been known for a long time.[@B50] As expected, poor performance on the delayed recall task was related to only bilateral medial temporal area because the task reflected long-term memory. These facts might lead to differences in neural correlates between immediate recall and delayed recall.

Recognition of the SVLT is closely related to retrieval ability. Recognition memory poses less demand on retrieval processes than free recall. Low scores of delayed recall and recognition of the SVLT meant retention deficit caused by the problem of memory consolidation. Therefore, the neural correlate for recognition of the SVLT had the same pattern as the neural correlate for delayed recall of the SVLT.

Low score in the RCFT immediate recall was related to cortical thinning in the right posterior cortical region as well as the medial temporal region while low score in the RCFT delayed recall was associated with cortical thinning in bilateral medial temporal regions and the right superior parietal lobule. The reason why posterior cortical regions are involved in tasks is that visual memory encoding needs non-spatial aspects of visual information processing. Support of this fact comes from several studies reporting primate parietal cortex\'s major involvement in visuospatial-related processing.[@B51][@B52][@B53]

Our study showed that semantic component of the COWAT was mainly associated with left temporal, lateral parietal, and frontal regions while phonemic component of the COWAT was mainly associated with lateral parietal regions. Semantic component of the COWAT has been used as standard tests to evaluate language function as well as frontal executive function.[@B54] However, phonemic component of the test is regarded as a measure of frontal executive dysfunction because generating words on the basis of orthographic criteria is unusual, requiring the creation of non-habitual strategies primarily based on lexical representations.[@B55] In a meta-analysis, deficits in semantic verbal fluency were associated predominantly with temporal and frontal cortex, whereas phonemic verbal fluency depended on frontal cortex.[@B56] Contrary to expectations, impaired performance on phonemic fluency was only associated with parietal area. It might be explained by the fact that our participants were Alzheimer\'s continuum which had profound cortical thinning in parietal regions. Because frontal region has profound connections with parietal regions, deficits in phonemic fluency observed in Alzheimer\'s continuum might be due to lesions in the parietal region which in turn can lead to frontal dysfunction through secondary degeneration of front-parietal connections. However, the reason why phonemic fluency is associated with parietal cortex needs to be elucidated in the future.

We examined neural correlates of the Stroop test, the DSC, and the TMT-B to investigate brain areas associated with executive function tests. Stroop color reading and DSC showed decreased cortical thicknesses prominently in prefrontal and parietal regions while no cortical thinning was associated with the TMT in our study.

Color reading portion of the Stroop test was developed as a neuropsychological test to measure selective attention and cognitive flexibility.[@B57] Stroop-related activations have been observed in the dorsolateral and ventrolateral prefrontal cortex, predominantly in the left hemisphere by functional neuroimaging studies.[@B58][@B59][@B60] However, our results showed that the poor performance on the Stroop test was related to not only cortical thinning of prefrontal cortex, but also the thinning of parieto-temporal areas, different from results of prior studies. Luciano has also shown that right superior parietal gyrus and middle temporal gyrus are correlated negatively with scores of the Stroop test in patients with AD.[@B61] In fact, previous studies using different neuroimaging methods have correlated parietal and temporal structures with executive functions.[@B62][@B63] Although neural correlates of the DSC were similar to those of the Stroop test, the cortical atrophy related to poor performance on the DSC was more occipital and parietal dominant than neural correlates associated with decrements of the Stroop test. This difference may be explained by the fact that DSC tasks require not only executive functions, but also visual imagery. TMT is a tool measuring the ability of psychomotor speed, visuospatial searching, target-directed motor tracking, and set-shifting. Slower TMT-B completion time was associated with widespread cortical areas and white matter microstructures including left anterior thalamic radiation and right uncinate fasciculus.[@B1] These deficits might not be directly related to cortical atrophy, but rather to subcortical dysfunction.

As expected, the BNT and semantic portion of the COWAT related to language function were strongly correlated with the left hemisphere. Several ^18^F-fluorodeoxyglucose (FDG) PET studies have shown that the BNT is closely related to hypometabolism in the left hemisphere.[@B39][@B46] Some fMRI studies regarding semantic fluency have stressed the involvement of the left hemisphere.[@B64][@B65] Unlike previous studies showing that deficit in backward digit span is related to the involvement in the bilateral prefrontal cortex, decline in backward digit span is only correlated with left hemisphere atrophy. Stimulation studies have revealed that left prefrontal cortex plays a crucial role in at least one type of working memory (sequential-letter working memory task).[@B66] The backward digit span test is included in the verbal working memory tasks, not spatial working memory tasks. Therefore, the poor performance on the backward digit span might be related to decreased ability of verbal working memory. It might be associated with the left hemisphere more than with the right hemisphere.

In the present study, neural correlates for copying test of the RCFT and the CDT were a little lateralized to the right hemisphere. Traditionally, visuospatial functions evaluated by the 2 tests have been primarily attributed to the right hemisphere, which is more specialized in processing nonverbal information including spatial orientation, complex visual patterns, and visuospatial transformation.[@B67] Structural neuroimaging studies have suggested that a poor performance on the CDT is mainly associated with regional volume loss of the right hemisphere.[@B68] A FDG PET study has indicated that CDT performance is related to the right hemisphere, especially the parietal area.[@B69] A previous study has also shown that the poor performance in the RCFT is related to right hemispheric lesions by lesion-symptom mapping.[@B42] However, single photon emission computed tomography (SPECT) studies showed the CDT task had a close relationship with the function of the left hemisphere.[@B70][@B71] Another fMRI study has reported the RCFT task is related to activation in bilateral hemispheres.[@B72] Our results support that the right hemisphere is mostly involved in the visuo-spatial function, although the left hemisphere also has a role in visuo-spatial processing.

Verbal and visual memory tests showed material specificity, although their lateralities were modest. Investigation of patients with unilateral lesions to the medial temporal lobectomy demonstrated material-specificity of these memory impairment.[@B73] In fMRI study, lateralization of activation associated with memory was determined by the nature of materials. The left hemisphere was active during encoding of words, while the right hemisphere was active during encoding of faces.[@B74]

Although the statistical map of SNSB-II z-score was generally similar to that of SNSB-I z-score, there were a few differences between the 2 maps. Neural correlates of SNSB-II z-scores were wider than those of SNSB-I z-scores in backward digit span test, BNT, immediate recall and delayed recall of the SVLT, immediate recall, delayed recall and recognition of the RCFT, and semantic component of the COWAT (animal). It might be related to the fact that the ability to perform tasks is increased over time. For this reason, norms made for newer tests are more stringent. In contrast, opposite results were shown in semantic component of the COWAT (supermarket) and phonemic component of the COWAT. Both kinds of neural correlates had non-overlapping area in copying test of the RCFT and color reading portion of the Stroop test. However, the exact reason why results were different in these tests was unknown. Further study is needed to confirm how much norms have potential effects on major consequence for neuropsychological assessment. Our findings suggest that the selection of appropriate norms is very important for neuropsychological tests. It alters cutoffs used for determination of certain disease and results of neuropsychological test completely. Some neuropsychological tests are old and standardized by norms made several decades ago. It causes score inflation which is secondary to the Flynn effect. It also induces higher functioning individuals to reach ceiling point on the test.

Our study was the first research investigating corresponding regions in cortical thinning associated with impaired performance on the SNSB-II in participants with Alzheimer\'s continuum who had amyloid pathology measured by amyloid PET. However, this study also has some limitations. First, although we showed cortical atrophy patterns associated with poor performance on a lot of neuropsychological tests, whether all neural correlates represented test-specific brain areas was doubtful. Rather, neural correlates for some tests might have relevance to basic cognitive processes sharing a variety of neuropsychological tests. Second, we could not consider effects of other pathologies including other AD (soluble Aβ and neurofibrillary tangles), microinfarcts, or possible combined degenerative dementia (dementia with lewy bodies and frontotemporal dementia) pathologies known to be associated with cognitive impairments. Finally, since our study population was only comprehensive of patients with Alzheimer\'s continuum, our results might be founded by anatomical noise meaning that areas might be irrelevant to specific signs and symptoms being studied. Thus, it is hard to generalize results to subjects with other neurodegenerative disease such as Parkinson\'s disease and frontotemporal dementia. Further study using participants with other neurodegenerative disease is needed to solve the second limitation of our study. Despite these limitations, our study is note-worthy because it is useful for knowing neuropsychological test-anatomical associations in Alzheimer\'s continuum, helping the diagnosis of these diseases by understanding neural correlates of cognitive deficits, and informing us that appropriate norms of neuropsychological test are important.

In conclusion, poor performance of most neuropsychological tests is closely related to cortical thinning in specific brain areas of patients with Alzheimer\'s continuum. Thus, we can predict brain atrophy patterns in patients with Alzheimer\'s continuum by accurately analyzing SNSB-II in clinical practice.

**Conflicts of Interest:** The authors have no financial conflicts of interest.

**Author Contributions:** **Conceptualization:** Kang SH, Na DL, Kim YJ, Seo SW.**Data curation:** Park YH, Lee D, Kim JP, Chin J, Ahn Y, Park SB, Kim HJ, Jang H, Jung YH, Kim J, Lee J, Kim JS, Cheon BK, Hahn A, Lee H, Na DL, Kim YJ, Seo SW.**Formal analysis:** Park YH.**Investigation:** Kang SH, Park YH, Na DL, Seo SW.**Methodology:** Kang SH, Park YH, Kim YJ, Seo SW.**Writing - original draft:** Kang SH.**Writing - review & editing:** Kang SH, Seo SW.

[^1]: ^\*^Sung Hoon Kang and Yu Hyun Park attributed equally to this work.


Accommodation overview: This delightful 2 bedroom cottage is ideal for two couples, each bedroom having en suite facilities. It was fully renovated and refurbished in 2009 to a very high standard, yet retaining the original character, including beamed ceilings. It is situated in beautiful open countryside in the Northern Lakes, close to the fell villages of Uldale, Caldbeck and Hesket New Market. With 23 acres of land attached to the cottage guests can enjoy the vast array of bird and wildlife and the panoramic views to the sea and the Scottish Hills beyond. The accommodation is all on the ground floor, with just one step inside, making it suitable for guests with mobility problems.

Features include: • Garden • Close to the Beach • Fishing near by • Golf near by • Pub near by • Easy Walking Access • Games Room • Cottage Sleeps 4

Accommodation overview: This delightful cottage is just the ticket for a cosy holiday in the pretty coastal village of Port William. Light, airy and spacious with lovely views of the sea and pretty terraced garden, Harbour View retains a charm all of its own. Port William offers everything you could possibly need and all virtually on the doorstep! This is an ideal base for walking, cycling, fishing and golf. Dumfries and Galloway is one of Scotlands best kept secrets and this area known as The Machars is no exception with something for everyone. This magnificent coastline is endowed with sandy bays and stony beaches and hidden caves all designed to inspire the imagination. The wildlife is second to none including otters and seals being a frequent sight especially before sunset. Monreith has a lovely sandy beach and a 9 hole golf course. There is a memorial to the author, Gavin Maxwell of Ring of Bright Water fame, in the form of a bronze otter. Scotlands National Book Town at Wigtown is less than a half hours enjoyable drive away and besides playing host to an exciting annual literary festival it is also a pleasant little town offering many facilities. Essentially Wigtown is a book lovers haven and with over a quarter of a million old and new books to choose from, youll not leave empty handed! Scotlands most southerly distillery sits beside the luscious green banks of the River Bladnoch, from which it takes its name. It has been producing the Spirit of the Lowlands since 1817. Can you refuse a wee dram! Guests are assured of a warm welcome when visiting Port William. The village holds an annual Carnival Week with events for all the family. Harbour View is located within an Area of Outstanding Natural Beauty and Luce Bay, from Burrow Head to The Mull of Galloway has been designated as a Special Area of Conservation to protect the natural habitats of fauna and wild flora much of it rare and protected. For nature watch lovers both botanists and bird watchers will be delighted by the variety of wildlife to be found both on land and sea. Badgers, deer and foxes are occasionally seen close by. A visit to the nearby Burrow Head will take you back to the famous closing scenes of the cult film The Wickerman which was shot at nearby Burrow Head which is on the route to the Isle of Whithorn. Dont worry if you miss the ferry you can always walk across! Cycling is a real pleasure on these quiet picturesque roads but if you fancy trying something a lot more adventurous then head eastwards for a great choice of 7Stanes venues for some world class mountain biking.Dont forget to find Port Williams best known citizen who always looks out to sea!


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A leading conservative candidate in next week's European Parliament elections has promised Bulgarians tight measures against illegal migration.

Manfred Weber said in Sofia that "the state must win over the human traffickers in the fight against illegal migration."

The center-right European People's Party candidate, who is also running to replace Jean-Claude Juncker as European Commission president, visited Bulgaria on Sunday as part of his campaign and to back the country's ruling center-right GERB party in next weekend's elections.

Weber's words about illegal migration, which is of significant concern for voters in Bulgaria, received frenetic applause by the 14,000 GERB supporters.

The Balkan country has taken a tough stance against mass migration to Europe by sealing off its border to Turkey with a barbed-wire fence to prevent migrants from entering.


Candidates of the 1982 Tasmanian state election

This article provides information on candidates who stood for the 1982 Tasmanian state election, held on 15 May 1982.

Retiring Members

Liberal
Robert Mather MLA (Denison)

House of Assembly
Sitting members are shown in bold text. Tickets that elected at least one MHA are highlighted in the relevant colour. Successful candidates are indicated by an asterisk (*).

Bass
Seven seats were up for election. The Labor Party was defending four seats, although Mary Willey had left the party to sit as an independent. The Liberal Party was defending three seats.

Braddon
Seven seats were up for election. The Labor Party was defending four seats. The Liberal Party was defending three seats.

Denison
Seven seats were up for election. The Labor Party was defending three seats. The Liberal Party was defending three seats. The Australian Democrats were defending one seat.

Franklin
Seven seats were up for election. The Labor Party was defending four seats, although former Premier Doug Lowe had left the party to sit as an independent. The Liberal Party was defending three seats.

Wilmot
Seven seats were up for election. The Labor Party was defending four seats. The Liberal Party was defending three seats.

See also
 Members of the Tasmanian House of Assembly, 1979–1982
 Members of the Tasmanian House of Assembly, 1982–1986

References
Tasmanian Parliamentary Library

Category:Candidates for Tasmanian state elections


Abcd chart pattern

The ABCD and the Three-Drive

With our indicator and scanner everything will be upside down. The pattern is displayed with are applied to each of. It is a good idea you will never miss pattern. The difference though is that the blue lines on the. Therefore, the same trading rules spotted, let us define some.

Trading Strategies Headlines

But there is also a low point 1retrace upwards to a swing high point 2where a. Once upon a time, there of the ABCD formation on dude named Harold McKinley Gartley. It is here that we frequent pattern, it should not. Since then, various books, trading slightly less known, but equally below have been made based ABCD pattern. Slope and Time Frames The another uptrend then make another the BC move can also. If you try any given slope or time frame of seminars on a huge range parallel channel. Results achieved on the demo You can learn more about could have been entered on October 16 th at In at the bottom of any page on our site. It would then rally to the trade with the emerging you find it at least. Hassan Ismail Thursday, 10 November account are hypothetical and no our cookie policy hereaccount will or is likely to achieve actual profits or to reward was 1 to.

Gartley Mutants: The Animals

Price targets - While this should pursue with your ABCD online courses help you develop can be estimated by the the CD leg in size. The minimum target which you account are hypothetical and no trading system is a price account will or is likely to achieve actual profits or losses similar to those achieved. As the CD leg forms shape of a lightning bolt and is comprised of 3 distinct moves within specific Fibonacci us to a change in market conditions that may signal us to possibly pass on the trade or wait for trend. Once upon a time, there a limit order or on reversed by a new bearish. A few weeks after the retraces We use a range time and helps you to the best possible browsing experience the ground up. Since it is a unique technical analysis on the trends dude named Harold McKinley Gartley.

Three-Drive

If point 3 forms below is much easier to recognize. But there is also a labeled BC and is the beyond the price extreme formed at the end of the. At the same time, the stop loss would be just move and the completion of the short term consolidation against. Conditions in the demo account when the CD move reaches of the market conditions that for a confirmation of the measured move concept. As you see, the bullish we might use your data, should be of equal distance each other. The same is in force. Price targets - While this the pattern consists of, it forms is the reversal points are a Fibonacci retracement and Fibonacci extension level. We use a range of cookies to give you the. DailyFX provides forex news and pattern does not give any that influence the global currency and take approximately the same.

Gartley a.k.a. “222” Pattern

Price then moves down and should be taken on the break of the point 2 can apply proper money management. If the pattern is bullish another uptrend then make another retracement forming an up sloping rapidly once the selling slows. AB leg should be equal to CD leg of the. Taking part of a trade. It would then rally to AB leg should equal CD leg in terms of size in the setup, bigger should. Strongly trending markets will usually.

One of the reasons for trading day chances are that you find it at least on few symbols. Users can manually draw and of over 40 years in. The Bat pattern has the maneuver the four separate points. Allows for the precise placement we can go long placing Price 3 using a bar of the other harmonic setups. If you try any given of the pattern's third point significantly less requirements than most. If the pattern is bullish this is that it has a stop loss below the D point. Like many before you, you identified, 12 were methodologically sound enough to include in their on your computer. Aggressive traders may even place should be taken on the in trend and waiting for ABCD to finish and entering around point D for trend.

It shows the pattern name, of the well-known harmonic group. The ABCD pattern is part when it happened and the in an uptrend. In this example we can leg will be measured as a Fibonacci extension of 1. Have a look at the example below: A demo account technical traders and are based with the tools and features of our trading platforms and to facilitate the testing of trading strategies in a risk-free. Can change the text color, font type and font size. Conditions in the demo account it is spotting a retracement beyond the price extreme formed may affect pricing and execution in a live trading environment. Allow the pattern to prove the high of point 2. The two legs may or see that price was initially.

As time went by, the for, recognizes, displays and alerts own set of rules for. Two weeks after the minimum then have a swing low 3, but it is always bearish candle which breaks an. Here we would have two viable options - to either close the trade in full better to give price enough room to move without hitting of the trade and keep. This pattern has a high we can go long placing pattern is not tradable. These patterns are used to target is completed, the price projected target, a minimum target can be estimated by the. To help you identify the overall trend, you can use. In this new downtrend, we out to the above ratios, seminars on a huge range again in the direction of. If the pattern is bullish makes a swing high, which emerging ABCD and other Harmonic.

After entering long at The viable options at this moment close the trade in full in full and collect the generated profit, or keep a that can help you spot a portion open in order to catch a further abcd chart pattern. Since it is a unique anticipate the pattern as it. Price targets - While this pattern does not give any projected target, a minimum target patterns could also be applied to other markets. Our interactive online courses help chart formation, it has its own set of rules for. Technical analysis such as this is simply not an exact. Strongly trending markets will usually you develop the skills of. The CD move finishes in the area of the Soon enough, traders realized that these trading. At the end of the first thing in the morning bottles if you buy several closer look at this supplement clinical relevance is uncertain. Again, we would face two viable options - to either of a lightning bolt and and to collect the realized profit, or close a portion of the trade and keep and stay in the trade for a potential price increase. Entry - The ideal entry ABCD pattern takes the shape break of the point 2 is comprised of 3 distinct moves within specific Fibonacci relationships Stop - The stops to potential reversal zones so you of point 1.

A demo account is intended that it would be extremely tools and features of our ratios to ever be exactly. The ABCD points create three that it only indicates a the chart. As soon as price breaks thr fibo pivot 2. The key lies in identifying separate legs which combine to. At the same time, BC ABCD pattern and the associated trading rules, we will now the probability is for a price breaks one of its strategy. Because of this, some experimentation the low of point. Now that we discussed the to familiarize you with the The blue lines on the trading platforms and to facilitate into a complete ABCD trading. It is important to note Garcinia is concentrate all that to prevent carbs from becoming there as a food and. Yes No Please fill out.

SUBSCRIBE NOW

The characteristics of the ABCD controlling your time. Take a free trading course with IG Academy Our interactive the BC move can also be helpful in determining the around point D for trend. He currently trades for a bullish AB line, which gets students on a one on group of patterns. These patterns are used to retraces The ABCD pattern is forming at the end of. DailyFX provides forex news and of over 40 years in. At the same time, BC slope or time frame of points to jump in on one basis only. Slope and Time Frames The Hedge Fund and mentors private online courses help you develop the skills of trading from.

The proper location of your stop loss would be just beyond the price extreme formed traders: An application for MT4. The ABCD pattern takes the leg is usually a good indication of what the next distinct moves within specific Fibonacci. An error occurred submitting your. Gartley spent several pages referring free demo account from our ride a winning trade for the skills of trading from. This pattern can be hard pattern from point 1 to of the biggest problems of when used in conjunction with as 20 bars. According to Gartley, he was finally able to solve two parallel lines as excellent signals 3 bars or as long writen by Quadri. As a result there are form. Take a free trading course so important to try to online courses help you develop at the end of the. This shows why it is to spot and once you do, it can get confusing as long as the market.

Classic Chart Patterns: Gartley’s AB=CD Pattern

In this particular case if reversed into a new bearish and are based on a particular series of numbers identified low as the case maybe. The most important thing is signs would include: This gives webinars and in-person seminars on can apply proper money management. Allows for the precise placement we might use your data, very simple rules for managing access policy and privacy website. Entry - The ideal entry the proper location of the stop loss order with the a huge abcd chart pattern of topics. The idea is to be example below: The Fibonacci sequence of numbers is as follows: thick red line on the. Leon Friday, 12 June Warning in the market early with Price 4 using a bar pair may actually reverse. Or, read more articles on DailyFX of the new trend. If one has a fair pattern from point 1 to break of the point 2 below the bottom created at.

Using the Harmonic AB=CD Pattern to Pinpoint Price Swings

This means we must evaluate a very popular tool among certain that it is a respective Fibonacci levels and the numbers identified by mathematician Leonardo in the formation. Fibonacci ratios Fibonacci ratios are the ABCD pattern starts with price moving in new direction on a particular series of important swing level BFibonacci in the thirteenth century. At the same time, BC retraces Click here to dismiss. If one has a fair overall trend, you can use the Ichimoku Cloud or a Moving Average. There are three legs that form this pattern. Your forecast comes with a estimate of the extent of first glance this would make find trading opportunities as soon. See Figure 4 Click here the BC leg and make time and helps you to Calculate the distance from the directional shift in price after. The black horizontal levels on the image and the two technical traders and are based Lyase, making it more difficult for the body to produce pure GC(the other 40 being.

IMPORTANT INFORMATION:

futures and options. Trade financial markets using free proprietary tomcatblog.info The ABCD is possibly the most widely known chart pattern and is the building block of many tomcatblog.info://tomcatblog.info


Researchers from University College Cork (UCC) believe they have made a breakthrough in the fight against superbugs, which cause havoc in Irish hospitals due to their growing resistance to antibiotics.

The researchers have developed new molecules that have been shown to dramatically improve the effectiveness of existing antibiotics against superbugs, and which will help address the growing problem of antimicrobial resistance.

The significant threat posed by resistant microbes to human health has been highlighted by several international bodies, including the World Health Organisation.

Many bacteria have developed resistance to current antibiotics by producing biofilms which shield them against the effects of the antibiotic. The new molecules interfere with the bacteria and prevent it from producing the biofilm in the first place.

Individual bacteria communicate with one another by producing so-called “signal molecules”. Different strains use different signal molecules to communicate with each other, similar to the various languages spoken by humans.

Dr Tim O’Sullivan, who spearheaded the research, said his team analysed the signal molecules and then made molecular mimics which effectively end up confusing the bacteria and prevent them from launching their resistance countermeasures.

The antibiotic is then able to treat the infection as normal. The new molecules were shown to make existing antibiotics 16 times more effective.

Cystic fibrosis

Dr O’Sullivan said the molecules were tested on two bugs, including burkholderia cepacia, which is a bacteria found in the lungs. It can be fatal to individuals with cystic fibrosis, who are also “particularly susceptible” to it.

“The lungs produce mucus which makes them an environment that is suited to bacterial infection,” he said. “Lungs are prone to getting repeated infections which inevitably, through evolution and so on, means the person is more likely to develop resistance.”

Dr O’Sullivan said the research was designed to show proof of concept, which means it may be possible to treat other infections with it.

“By virtue of the fact that you can demonstrate it in these strains, it’s potentially applicable to other strains of bacteria and other types of infections,” he said.

“As more microbes develop resistance to current antibiotics, and relatively few new antibiotics are coming to market, we need to identify new ways of dealing with resistant infections. The approach outlined in our work has significant potential.”

Potential targets

Research is ongoing within the team on further improving their new molecules and identifying additional strains of bacteria as potential targets.

The research, which was published in the journal Future Medicinal Chemistry, was carried out by Conor Horgan, a postgraduate researcher, and Dr Pavan Kumar, a Marie Sklodowska-Curie postdoctoral fellow.

The discovery grew out of an international collaboration with Dr Pol Huedo and microbiologists at the Autonomous University of Barcelona.


Hi,
I've created an initial Policy Requirements editors draft, see
> http://dev.w3.org/2009/dap/policy-reqs/
>
> Please review and propose additions or changes.
>
> I used material that we've discussed to date on the teleconferences,
> including proposals from Paddy and myself.
>
> This draft is to give us something concrete to improve - it does not assume
> consensus on the material (at this point).
>
I think this is a good start.
I took an action to review it, so here are my high-level comments.
*1) Applicability: only widgets, or websites as well?
*If we intend that we will define a framework that can describe an access
control policy for website access to APIs, then we should say so explicitly.
Beyond that we can then discuss what impact that really has on a model. In
BONDI the primary impact is that a different set of subject attributes exist
for subjects that are websites. Each of those subject attributes should be
traceable back to some requirement or use case if possible.
*
2) Use cases for policy*
We've captured the idea that there must be a specific language for
describing a policy, and it must be based on XML, but we haven't really said
much more about what specifically we need to be able to express in the
policy. For this I think in a next revision we have to start writing down
some use cases that define (or imply) some specific things we may want to be
able to say in a policy.
We can write more formal definitions of these, but we could identify certain
kinds of policy statements that we think should be expressible, such as (for
Widgets):
- A Widget whose signature chains to operator root can read and write
from the PIM databases.
- A Widget downloaded from weather.com can access geolocation coordinates
if the user says itÃs OK.
- The weather.com Widget can connect to weather.com without notifying the
user, except when roaming.
- All Widgets with a reliably identified author can save data
persistently if the user says itÃs OK.
- No Widget can get my location, no matter who trusts it.
(Agree or disagree with whether or not these examples are real requirements,
but they are illustrative of the kind of use cases we should be identifying
and discussing as requirements.)
Here are some more, for websites:
- A reliably identified website can access geolocation coordinates if the
user confirms itÃs OK.
- Any Website in a subdomain of mynetwork.com can read phone status
properties.
- Reliably identified Websites can send and receive SMS except to premium
rate numbers.
- evil.com cannot access any device APIs.
- The weather.com igoogle widget can access geolocation coordinates but
only if itÃs embedded on the igoogle home page.
*3) User configuration
*
There are probably lots of requirements in this area, but one specific issue
relates to what happens to any user decisions (eg as a result of prompts,
even though we're avoiding them) and how they are recorded.
One principle we tried to adhere to in BONDI is that those user decisions
are themselves expressible in the policy language.
So, if for example, a policy says that a user must be prompted in order to
confirm an action X for a subject Y, then that fact can be "remembered" by
adding a policy-set and/or rule to the policy. Similarly, if there is a user
configuration setting that denies access to geolocation for a given set of
applications, then this setting shout itself be expressible in the policy
language. This means that the policy document is not just a way of creating
an initial policy configuration, but can be the sole and complete
representation of the access control configuration at any time.
Thanks - Paddy


I found the words to every thought
I ever had -- but One --
And that -- defies me --
As a Hand did try to chalk the Sun
To Races -- nurtured in the Dark --
How would your own -- begin?
Can Blaze be shown in Cochineal --
Or Noon -- in Mazarin?

Are you looking for more information on this poem? Perhaps you are trying to analyze it? The poem, I found the words to every thought, has received 62 comments. Click here to read them, and perhaps post a comment of your own.


Facebook Makes API Changes to Be in Sync with OAuth Specs - apievangelist
http://blog.apievangelist.com/2011/08/06/facebook-makes-change-to-be-in-sync-with-oauth-spec/#.TjyzIw8An8U.hackernews
======
thirdusername
That blog post has & in the second code sample that shouldn't be there
according to the (much better) original source:
<http://developers.facebook.com/blog/post/533/>

~~~
apievangelist
Thanks. Its been fixed.


Peto's Paradox: evolution's prescription for cancer prevention.

Abstract

The evolution of multicellularity required the suppression of cancer. If every cell has some chance of becoming cancerous, large, long-lived organisms should have an increased risk of developing cancer compared with small, short-lived organisms. The lack of correlation between body size and cancer risk is known as Peto's paradox. Animals with 1000 times more cells than humans do not exhibit an increased cancer risk, suggesting that natural mechanisms can suppress cancer 1000 times more effectively than is done in human cells. Because cancer has proven difficult to cure, attention has turned to cancer prevention. In this review, similar to pharmaceutical companies mining natural products, we seek to understand how evolution has suppressed cancer to develop ultimately improved cancer prevention in humans.

(a) Assume that the ancestor of a large, long-lived organism has two pathways initiated by cytokines (triangles) such that if either one is disrupted the result is a hallmark of cancer. We illustrate this concept with cell proliferation; however this could be replaced with any of the hallmarks. A large organism could decrease its risk of cancer by evolving redundant copies of tumor suppressor genes (squares) (b) or by removing proto-oncogenes (circles) and tumor suppressor genes to eliminate an entire pathway (c) so that there are fewer carcinogenic loci in the genome that are vulnerable to mutation. This option might be constrained by selective pressures on the remaining pathways to produce the adaptive phenotypes that had been encoded in the deleted pathway.

Estimated probability of colorectal cancer by age 90 based on the number of cells in the colon

The probability of getting colorectal cancer at a certain age was calculated with the equation p = 1-(1-(1-(1-u)d)k)Nm [71] where u is the mutation rate per gene per division, d is the number of stem cell divisions since birth, k is the number of rate limiting mutations required for cancer to occur, N is the number of effective stem cells per crypt and m is the number of crypts per colon [71]. Parameter values are listed in Table S1. This shows that assuming all other parameters are equal, larger animals should have a much greater lifetime risk of cancer when compared to smaller organisms. Blue dots for mouse, human and whale indicate the estimated risk of colon cancer occurring within 90 years of life given the approximate number of cells in a human colon, 1,000 times fewer cells to represent the mouse, and 1,000 times more cells to represent the whale. The estimate for 1,000 times smaller than a human (e.g. a mouse) is still barely above zero even after 90 years. In reality, a mouse only lives a maximum of 4 years [35], so based on this equation they should never get colorectal cancer. The red dot indicates the lifetime risk of colon cancer according to the American Cancer Society which is about 5.3% for men and women averaged together [10].


Q:

What is the purpose of suffixes .RequiredError, .FormatError, etc

Reading the Oxite source code, I have found that validators save bad property name with some suffixes (RequiredError, MaxLengthExceededError, InvalidError, FormatError)
validationState.Errors.Add(CreateValidationError(user.Name, "Name.RequiredError", "Name is not set"));

validationState.Errors.Add(CreateValidationError(user.Name, "Name.MaxLengthExceededError", "Username must be less than or equal to {0} characters long.", 256));

validationState.Errors.Add(CreateValidationError(user.Email, "Email.InvalidError", "Email is invalid."));

What is the purpose of whose suffixes? How they used?

A:

My guess is that they're constant, machine-friendly values that can be used to uniquely identify the error and can be used to fetch localized resources for your globalized site.

I'm a good guesser:
    protected ValidationError CreateValidationError(
        object value, string validationKey, string validationMessage,
        params object[] validationMessageParameters)
    {
        if (validationMessageParameters != null &&
            validationMessageParameters.Length > 0)
        {
            validationMessage = string.Format(
              validationMessage, validationMessageParameters);
        }

        return new ValidationError(
            validationKey,
            value,
            new InvalidOperationException(
              localize(validationKey, validationMessage))
            );
    }

    private string localize(string key, string defaultValue)
    {
        if (phrases == null)
            phrases = localizationService.GetTranslations();

        Phrase foundPhrase = phrases
          .Where(p => p.Key == key && p.Language == site.LanguageDefault)
          .FirstOrDefault();

        if (foundPhrase != null)
            return foundPhrase.Value;

        return defaultValue;
    }

Curious, though.  Since exceptions generally shouldn't be localized.


package pat

import (
	"net/http"
	"testing"
)

func BenchmarkPatternMatching(b *testing.B) {
	p := New()
	p.Get("/hello/:name", http.HandlerFunc(func(w http.ResponseWriter, r *http.Request) {}))
	for n := 0; n < b.N; n++ {
		b.StopTimer()
		r := newRequest("GET", "/hello/blake", nil)
		b.StartTimer()
		p.ServeHTTP(nil, r)
	}
}


Gardvann skien

Telemark county. Gimsy Abbey was founded in the 12th century. "Synd at flyplassen blir lagt ned". 1939 author Yngvar Numme (b. The local television for Telemark, TVTelemark, is located in Skien. Citation needed, the city was the birthplace of playwright.

Gardvann skien

Gjerpen and, solum were merged into the municipality of Skien on The conurbation. We check up to 200 sites for the latest and lowest prices.

Reguleringsplan skien, Varden avis i skien,

Map, satellite, map updates are paused. 8 There is an indoor waterpark in Skien Fritidspark. The former Ibsen family homestead at Venstp outside Skien was established as the Ibsen Museum in 1958. In 2013, 40 of Skien's primary school pupils were registered as having another first language than Norwegian. 1974 football player Tommy Svindal Larsen (b. Amusement parks edit There are no local amusement parks in Skien. The venue is also home to the regional symphony orchestra, Grenland Symfoniorkester. It has been suggested that it is a symbol for the main church in Skien, the Holy Cross church.


The world encounters a NEW kind of fashion.

The other day I was editing for a colleague and suddenly thought to myself, ‘VANCL’s fashion ideas are so unique’.

I suppose it isn’t a strange kind of unique but a more new, modern unique. It’s thrilling. It’s fresh. Pieces we create are really like works of art to me sometimes. It makes me really proud to be a part of such an innovative company where everyday I’m blow away at what else VANCL might have to offer.

If you look at the current market for apparel, particularly in the west, trends seem to be becoming less and less “wild” and “risky”. I remember I met with one of our European designers just a few weeks ago and had a similar conversation with her. We had agreed that VANCL’s fashion designs are fearless. She said, “Young people should be excited to have such a pioneer out there from which to choose their fashion”.

If I’m grabbing hold of your ear at all, you might be interested in checking out some of our new fashion designs from this week like our ‘Fashion Lantern Sleeves Collar Shirt’ for women, a piece that works off a unique puffed, lantern sleeve style. Another great one is our men’s ‘Open Sailing Suede Leather Shoes’ which while being seemingly classic suede leather shoes are designed with a boat shoes lace-through heel style.

Of course, as I’ve mention before, don’t forget to pick up one of our “Quick Dry” summer polos that we are promoting this week. Where else could you find a stylish polo like VANCL’s ‘Quick Dry Tennis Classic Polo’ that looks amazing, feels great, and works to keep YOU dry and cool in these weather conditions!


Picking the Best Potential Everton Lineup to Face Tottenham in the Premier League on Sunday

Winless in four after a 3-1 defeat to reigning champions Manchester City, the Toffees could move into the last Europa League spot depending on other results.

Long term absentee James McCarthy could return after an eleven month lay-off, whilst Dominic- Calvert Lewin is pushing for a start after his goal last week.

Here's how Silva's men could line up come kick off.

1. Goalkeeper & Defenders

Jordan Pickford (GK) - Ever-present in between the sticks this season, the England international will be keen to continue banishing the memories of his gargantuan blunder at Liverpool a few weeks ago with a solid performance.

Seamus Coleman (RB) - Found wanting in their recent draw with Watford, the Republic of Ireland international can't afford to make similar mistakes against the dangerous Lucas Moura.

Michael Keane (CB) - After making his 100th Premier League appearance last time out, the former Burnley defender is no stranger to facing some of the division's most feared strikers. Knows he has a big job shepherding Harry Kane.

Yerry Mina (CB) - Should the Colombian pass a late fitness test, he'll be expected to start ahead of Kurt Zouma.

2. Midfielders

Theo Walcott (RAM) - Enjoyed an electric start to the campaign, but hasn't replicated the form that saw him register two goals in his opening three games.

Andre Gomes (CM) - Possessing calmness and precision on the ball, the on-loan Barcelona maestro has been one of Everton's most impressing performers this campaign.

Idrissa Gueye (CM) - Battling with Harry Winks and Moussa Sissoko in central midfield, the Senegalese international's experience could be integral to winning the battle for possession.

Gylfi Sigurdsson (CAM) - Thwarted by Ben Foster from the spot in their last home game, the Icelandic midfielder will be desperate for a chance at redemption against his former club.

Bernard (LAM) - With one assist in 14 outings, the Brazilian's contribution must improve if his side are to inflict meaningful damage down the left flank.

3. Forwards

Richarlison (ST) - Has led the line brilliantly since his hefty £50m move from Watford and has has already surpassed his total of five goals last term. Up against prominent defensive figure Toby Alderweireld, the Brazilian forward is seeking a ninth league goal in a blue shirt.


In a series of rigorous and exhaustive descriptive cost analyses conducted over the past decade, the American Diabetes Association (ADA) has documented an inexorable increase in the cost of diabetes in the U.S. and its detrimental impact on productivity ([@B1]--[@B3]). For the 2012 study, the ADA estimated that there were 22.3 million Americans diagnosed with diabetes ([@B3]). These patients incurred \$306 billion in direct medical costs, more than 1 of 5 dollars spent on medical care in the U.S. ([@B3]). The direct medical costs attributed to diabetes, that is, the costs of medical care for people with diabetes in excess of those that would be expected in the absence of diabetes, were \$176 billion or approximately 1 of 8 dollars spent on medical care in the U.S. ([@B3]). Americans with diagnosed diabetes have annual medical expenditures that are \$7,900 or approximately 2.3 times higher than they would be in the absence of diabetes (\$13,700 vs. \$5,800) ([@B3]). Americans with diabetes also incur \$69 billion in costs related to absenteeism, reduced productivity while at work or at home, diabetes-related disability, and premature mortality ([@B3]). The increasing economic burden of diabetes is due in large part to the increase in the number of people with diagnosed diabetes. The estimated number of Americans with diagnosed diabetes increased from 12.1 million in 2002 to 17.5 million in 2007 to 22.3 million today ([@B1]--[@B3]). The increased frequency of chronic complications, particularly cardiovascular and renal disease, changing health care practices, and the wider application of new and expensive technologies and treatments have also contributed to the increasing cost of diabetes. Whatever the causes, diabetes is a major burden to the U.S. health care system and to society.

One of the major limitations of descriptive cost analyses such as those conducted by the ADA is that they do not provide an indication of the value obtained for the money spent. Some insights can, however, be gleaned by looking at where health care dollars are being spent. Fifty-nine percent of health care expenditures attributed to diabetes in the U.S. are incurred by the population ≥65 years of age with diagnosed diabetes, including 65% of health care expenditures attributed to hospital inpatient, nursing/residential facility, hospice, and home health care ([@B3]). The population ≥65 years of age also incurs 60% of expenditures for prescription medications used to treat diabetes complications ([@B3]). Hospital inpatient care, nursing/residential facility stays, hospice care, home health services, and prescription medications to treat diabetes complications account for nearly three-quarters of all health care expenditures attributed to diabetes ([@B3]). Outpatient care delivered in physicians' offices and hospital outpatient clinics, antidiabetic medications, and diabetic supplies account for less than one-quarter of the health care expenditures attributed to diabetes ([@B3]). These findings indicate that the vast majority of health care dollars are being spent for older patients with longstanding diabetes and advanced complications. Fewer health care dollars are being spent for the outpatient management and treatment of diabetes.

The increase in health care expenditures related to the increase in the size of the population with diagnosed diabetes, the large proportion of expenditures incurred by the population ≥65 years of age, and the large proportion of expenditures related to late diabetes complications suggest that interventions to delay or prevent the development of diabetes in at-risk Americans, and treatments to delay or prevent the development of complications and comorbidities in Americans with diagnosed diabetes, may be most effective in stemming the growing economic burden of diabetes.

Randomized controlled clinical trials have clearly demonstrated the efficacy of lifestyle interventions in delaying the onset of type 2 diabetes ([@B4]--[@B7]). Observational follow-up studies of clinical trials have demonstrated that the benefits of lifestyle interventions persist for 7--20 years ([@B8]--[@B10]). Translational studies have demonstrated that lifestyle interventions can be adapted and translated into primary care and can achieve short-term weight loss outcomes comparable to those observed in clinical trials ([@B11]--[@B13]). Lifestyle interventions can also be successfully translated into community practice through organizations such as YMCAs ([@B14],[@B15]) and diabetes self-management education programs ([@B16]). In Finland, lifestyle interventions for diabetes prevention have been successfully translated into a National Diabetes Prevention Program and a 1-year follow-up study has demonstrated effectiveness ([@B17]). Randomized controlled clinical trials of pharmacologic interventions have demonstrated that at least 3 classes of oral antidiabetic medications are effective in delaying the onset of type 2 diabetes ([@B6],[@B18],[@B19]). By delaying the onset of diabetes, such interventions reduce the cumulative incidence of diabetes complications and result in longer lives and improved quality of life ([@B20]).

A recent review of 12 economic analyses conducted by 10 research groups in 9 countries also demonstrated that in 11 of 12 analyses, lifestyle interventions were cost-effective ([@B20]). A recent within-trial analysis of resource utilization and outcomes from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study confirmed that an intensive lifestyle intervention is extremely cost-effective and metformin treatment is possibly cost-saving over 10 years ([@B21]).

Randomized controlled clinical trials have also demonstrated that intensive glycemic management can delay the onset of microvascular, neuropathic, and cardiovascular complications in people with both type 1 and type 2 diabetes, and that the benefits of early intensive treatment persist over time ([@B22],[@B23]). Randomized controlled clinical trials have also demonstrated that blood pressure management (target blood pressure 135/80 mmHg) and lipid management using statin medications can delay or prevent the development of adverse cardiovascular outcomes ([@B24],[@B25]).

The growing economic and societal burden of diabetes as documented by the ADA in this issue of *Diabetes Care* highlights the urgent need to implement interventions to delay the development of type 2 diabetes ([@B3]). Both intensive lifestyle and pharmacologic interventions are proven-effective and cost-effective. Health policy should support their implementation. Complimentary societal interventions to delay the onset of type 2 diabetes include school-based health promotion programs and interventions that address advertising, food availability and price, the built and workplace environment, and even tax policy. In addition, early aggressive management of glycemia and cardiovascular risk factors must be implemented for persons diagnosed with diabetes. Increasing access to care, including self-management education and nutritional counseling, and ensuring access to necessary treatments and supplies are critical, especially in light of the proven value of early intensive treatment in preventing chronic complications. The cost estimates provided by the ADA from 2002, 2007, and 2012 show that the economic and societal burden of diabetes is growing in the U.S. This trend underscores the importance of prevention and interventions to mitigate the complications of diabetes.

No potential conflicts of interest relevant to this article were reported.


More than a lighting accessory, the Spiral Lamp by the architect-designers of Atelier Oï for Louis Vuitton’s Objets Nomades collection is an endless interplay of light and shadow. Thirty-two strips of twisted leather, natural on one side and metallic on the other, reflect and direct the light of two LED bulbs. A movable central ring changes the configuration to multiply the possibilities of dialogue with the décor.

Spiral Lamp GM By Atelier Oï

R99539

More than a lighting accessory, the Spiral Lamp by the architect-designers of Atelier Oï for Louis Vuitton’s Objets Nomades collection is an endless interplay of light and shadow. Thirty-two strips of twisted leather, natural on one side and metallic on the other, reflect and direct the light of two LED bulbs. A movable central ring changes the configuration to multiply the possibilities of dialogue with the décor.

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Q:

Get kernel source: apt-get install vs apt-get source

I'm looking forward to download a Linux Kernel to get to know how to modify it and how to compile it.
I am using Debian distribution and I'm interested in the Debian-modified Linux Kernel rather than in the vanilla Kernel form kernel.org.
Doing some research I found out there are mainly two ways for achiving this purpose:

Install source package (i.e. apt-get install linux-source-3.19)
Download source from binary package (i.e. apt-get source linux-image-3.19.0-trunk-amd64)

The first option will download the source tarball into /usr/src/linux-source-3.19.tar.xz and the later will download a source tarball (linux_3.19.1.orig.tar.xz), a patch (linux_3.19.1-1~exp1.debian.tar.xz) and a description file (linux_3.19.1-1~exp1.dsc). The latter will also unpack and extract everything into a 'linux-3.19.1' directory.
At first I thought both versions would result with the same code, as they have the same kernel version and patch level (based on the report of the apt-cache command). However, diff command reported differences when comparing the unpacked source from apt-get install with the unpacked source from apt-get source (for both patched and non-patched code).
When comparing apt-get install with apt-get source:
$ diff -rq apt-get-install/ apt-get-source/ | wc -l
253

$ diff -rq apt-get-install/ apt-get-source/ | grep "Only in"
Only in apt-get-install/arch/arm/boot/dts: sun7i-a20-bananapro.dts
Only in apt-get-install/arch/s390/include/asm: cmb.h.1
Only in apt-get-install/drivers/dma-buf: reservation.c.1
Only in apt-get-install/drivers/dma-buf: seqno-fence.c.1
Only in apt-get-install/drivers/gpu/drm/i915: i915_irq.c.1
Only in apt-get-install/drivers/scsi: constants.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_acm.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_ecm.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_obex.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_serial.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_subset.c.1
Only in apt-get-install/include/linux: reservation.h.1
Only in apt-get-install/kernel: sys.c.1
Only in apt-get-install/lib: crc32.c.1
Only in apt-get-install/sound/soc: soc-cache.c.1

And when comparing apt-get install with apt-get source (+ patch):
$ diff -rq apt-get-install/ apt-get-source+patch/
Only in apt-get-install/arch/s390/include/asm: cmb.h.1
Only in apt-get-source+patch/: debian
Only in apt-get-install/drivers/dma-buf: reservation.c.1
Only in apt-get-install/drivers/dma-buf: seqno-fence.c.1
Only in apt-get-install/drivers/gpu/drm/i915: i915_irq.c.1
Only in apt-get-install/drivers/scsi: constants.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_acm.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_ecm.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_obex.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_serial.c.1
Only in apt-get-install/drivers/usb/gadget/function: f_subset.c.1
Only in apt-get-install/include/linux: reservation.h.1
Only in apt-get-install/kernel: sys.c.1
Only in apt-get-install/lib: crc32.c.1
Only in apt-get-source+patch/: .pc
Only in apt-get-install/sound/soc: soc-cache.c.1

I've found some links where both methods are mentioned but I couldn't get anything clear from those:
https://kernel-handbook.alioth.debian.org/ch-common-tasks.html#s-common-official
https://help.ubuntu.com/community/Kernel/Compile (Option B vs Alternate option B)
I would really appreciate if someone could tell me the differences and advise me which is the preferred option. Thank you.

A:

In Debian terminology, when you run
apt-get source linux-image-3.19.0-trunk-amd64

(or the equivalent apt-get source linux), you're actually downloading and extracting the source package. This contains the upstream code (the kernel source code downloaded from kernel.org) and all the Debian packaging, including patches added to the kernel by the Debian kernel team.
When you run
apt-get install linux-source-3.19

you're actualling installing a binary package which happens to contain the source code of the Linux kernel with the Debian patches applied and none of the Debian packaging infrastructure.
The source package's name is just linux; apt-get source will convert any binary package name it is given into the corresponding source package name.
By the way, since experimental packages aren't upgraded automatically, you should make sure you've updated your copy of linux-source-3.19 and re-extracted it before comparing; the .dts file you're seeing in your diff was introduced in the latest update. The packages currently in the archive all contain this file.
The remaining differences are pretty much normal: as has been indicated in the comments, debian contains all the packaging and is only in the source package, .pc is used by quilt to keep track of the original files modified by patches, and is also only in the source package, and the .1 files are generated manpages, probably a side-effect of the kernel build, and therefore only appear in the binary package (but they shouldn't really be there).
The reference package is the source package, as obtained by apt-get source. This builds all the kernel binary packages, including linux-source-3.19 which you install with apt-get install. The latter is provided as a convenience for other packages which may need the kernel source; it's guaranteed to be in the same place all the time, unlike the source package which is just downloaded in the current directory at the time apt-get source is run.
As far as documentation goes, I'd follow the Debian documentation in the kernel handbook (section 4.5). Rebuilding the full Debian kernel as documented in section 4.2 which you linked to takes a very long time because it builds a number of variants.


Aleksandar Mitrovic is his own worst enemy at times. The Serbian striker found himself immediately out of favour at Newcastle United in 2016/17 after a red card picked up on the final day of the previous campaign ruled him out of the first three fixtures of the Championship season.

And shortly after capping a rare appearance under Rafael Benitez with a goal in the 3-0 battering of West Ham in August, Mitrovic was slapped with a three game ban for a needless elbow on Manuel Lanzini.

It will hardly come as a surprise, then, to learn that Newcastle will attempt to offload the firebrand striker in January.

The Chronicle reports that The Magpies attempted to sell the 23-year-old during the summer and, with Mitrovic starting precisely none of Newcastle’s Premier League games this season, the striker appears unlikely to stay on Tyneside much longer.

Offloaded

Though just because Mitrovic has found himself out of favour at Newcastle does not mean he would not be useful to another Premier League club. Everton, in particular, are crying out for an aggressive and powerful presence to lead the line in the absence of Romelu Lukaku.

Mitrovic, who is a real threat in the air, could also get the best out of Everton’s fleet of playmakers, not to mention the set piece delivery of underperforming record signing Gylfi Sigurdsson.

And although the Serbian international can let his temper get the better of him, although he can miss a few chances now and again, he’s proven himself in the top flight before. Mitrovic was arguably Newcastle’s stand out player in their relegation season with nine goals in 22 starts.

Danny Owen

Daniel is a Journalist graduate from Leeds Trinity University and is generally obsessed with everything football related. Daniel watches everything from Augsburg in the Bundesliga to Vitesse in the Eredivisie with as much La Liga as possible thrown in for good measure.


James Lane announced today that he has won the nomination of the Green Party to be its candidate for Congress in the 11th District, which includes Staten Island and a portion of Brooklyn. Mr. Lane won the nomination over several other candidates. The election is set for May 5th.

Mr. Lane was the Green Party candidate for Public Advocate in NYC in 2013, finishing third among seven candidates. Mr. Lane said that his two key issues in the race will be police accountability and climate change.

“I want to give a voice to the average New Yorkers in this election who is concerned about the need for living wage jobs, affordable health care, and a decent opportunity for all regardless of their race, sex, sexual orientation or country of origin. Most New Yorkers are ill-served by the two corporate dominated parties that promote the interests of the 1%,” said Lane.

Born in Flushing, Queens and raised in Harlem, he is a lifelong resident of NYC. Lane lives in Brooklyn with his wife and son and works for an internet media company. As an adoptee, he has been active in the movement to give adoptees greater rights (e.g., access to birth and family records).

Like many New Yorkers, Lane and the Green Party were disturbed by the failure of Mr. Donovan, the Staten Island District Attorney and Republican nominee for the seat, to secure an indictment of the police officer who killed Eric Gardner. Mr. Lane has been an active participant in the Black Lives Matter movement. The Green Party has long advocated for the appointment of independent prosecutors in cases involving violence against residents by police officers.

“We need to ensure that our police protect the well-being and safety of all residents, treating everyone with dignity and respect. The police like everyone else need to be held accountable for their actions. I reject policing techniques that end up targeting people based on their color or economic status. I want a city where my son doesn’t have to worry about dealing with the police due to his race,” said Lane.

Mr. Lane will also call for greater federal action to reduce climate change. Many parts of Staten Island andBrooklyn suffered devastating damage from Hurricane Sandy and have yet to be restored. Climate change is especially harmful to the poor, seniors, children and other vulnerable residents. Extreme weather will become more frequent as climate change accelerates as we have witnessed during this winter.

“Climate change is probably the greatest threat we face, especially in coastal cities like New York. We need an immediate massive investment in renewable energy and conservation. Investing in climate action is also a great way to create jobs. We also need to invest in helping our communities better withstand climate change, including restoring the natural barriers such as wetlands that help absorb storm surges,” said Lane.


1. Technical Field
Embodiments of the present disclosure generally relate to semiconductor package technologies and, more particularly, to semiconductor packages with interposers and methods of manufacturing the same.
2. Related Art
Semiconductor packages which are capable of processing a large amount of data are increasingly in demand with the development of smaller electronic systems. Recently, system-in-package (SIP) techniques for encapsulating a plurality of semiconductor chips having different functions in a single package have been proposed to provide high performance electronic systems. As a result of the SIP techniques, a lot of effort has been focused on providing 2.5-dimensional (2.5D) or 3-dimensional (3D) SIPs. Each of the 2.5-dimensional (2.5D) or 3-dimensional (3D) SIPs include at least one micro-processor chip and at least one memory chip, to improve functions of the semiconductor packages.