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COG-320 - IBM Cognos Xcelerator and Advisor V.9 - Dump Information

Vendor	:	IBM
Exam Code	:	COG-320
Exam Name	:	IBM Cognos Xcelerator and Advisor V.9
Questions and Answers	:	180 Q & A
Updated On	:	November 10, 2017
PDF Download Mirror	:	COG-320 Brain Dump
Get Full Version	:	Pass4sure COG-320 Full Version

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COG-320 Questions and Answers

Answer: A

QUESTION: 173

When using Xcelerator, in which order are calculations performed in rules?

Addition, Subtraction, Division, Multiplication, Exponentiation
Addition, Subtraction, Exponentiation, Multiplication, Division
Multiplication, Division, Addition, Subtraction, Exponentiation
Exponentiation, Multiplication, Division, Addition, Subtraction

Answer: D

QUESTION: 174

Which statement is used to force the TM1 consolidation engine to always use the sparse consolidation engine in Xcelerator?

FEEDERS
STET
CONTINUE
SKIPCHECK

Answer: D

QUESTION: 175

A drill process is one of two main components of drill -through in Xcelerator. What is the other component of drill-through?

drill folder
query
drill assignment rule
cube reference Answer: C QUESTION: 176

Which Turbo Integrator procedure, within the Advanced tab, may consist of a series of actions that are to be executed before the data source is processed in Xcelerator?

epilog
prolog
parameters
metadata

Answer: B

QUESTION: 177

When no qualifier is used in a rule, to which two types of elements does Xcelerator assume the rule applies? (Choose two.)

leaf
consolidation
string
text

Answer: A, B

QUESTION: 178

Which three characteristics are true when describing chores in Xcelerator? (Choose three.)

You must select the process for which you want to create a chore.
Chores can only be scheduled to execute twice a day.
You must define the intervals at which the chore is executed.
Once a chore is created it cannot be edited; you must re -create the chore in order to modify it.
Chores will not be activated unless the Activate Chore box is checked.

Answer: A, C, E

QUESTION: 179

What are two reasons for building a cube in Xcelerator? (Choose two.)

You want to conduct multi-dimensional analysis of your data.
You want to collect data from various members of staff.
You want a structure to replace a transactional database.
You want to be able to create complex formatted reports for board members.

Answer: A, B

QUESTION: 180

It is recommended that you develop a naming convention for your cubes to make maintenance and expansion of your model easier. Which statement is true regarding the order that cubes are displayed in Xcelerator?

Cubes are displayed in the order that they are created.
Cubes are displayed in alphabetical order.
Cubes can be arranged into any order that is required.
Cubes should always be prefixed with a number for correct ordering.

Answer: B

IBM COG-320 Exam (IBM Cognos Xcelerator and Advisor V.9) Detailed Information

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IBM COG-320

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MRI as a Biomarker of sickness development in a Therapeutic Trial of Milameline for ad Neurology. author manuscript; obtainable in PMC 2009 Sep 16.
published in last edited kind as:
PMCID: PMC2745302
NIHMSID: NIHMS136225
C. R. Jack, Jr., M.D., M. Slomkowski, Pharm.D., S. Gracon, D.V.M., T. M. Hoover, Ph.D., J. P. Felmlee, Ph.D., ok. Stewart, B.S., Y. Xu, M.D., Ph.D., M. Shiung, B.A., P. C. O'Brien, Ph.D., R. Cha, M.S., D. Knopman, M.D., and R. C. Petersen, Ph.D. M.D. Departments of Diagnostic Radiology (CRJ, YCX, JPF, YCX, KS, MS), Neurology (DK, RCP), and Biostatistics (PCO, RC) Mayo clinic and groundwork, 200 First street SW, Rochester, MN 55905. Pharmaceutical analysis (MS, SG, TMH) Parke-Davis (Pfizer), 2800 Plymouth road, Ann Arbor, MI 48105
Corresponding author: Clifford R. Jack Jr., M.D. Mayo medical institution Diagnostic Radiology 200 First street SW Rochester, MN 55905 cellphone: 507-284-8548 FAX: 507-284-2405 ; e mail: ude.oyam@droffilc.kcaj The publisher's last edited edition of this text is available at Neurology See different articles in PMC that cite the posted article. summary purpose

To investigate the feasibility of the usage of magnetic resonance imaging (MRI) measurements as a surrogate conclusion point for sickness progression in a therapeutic trial for Alzheimer's disease (advert).

methods

Three-hundred-sixty-two sufferers with possibly ad from 38 diverse centers participated in the MRI element of a 52 week randomized placebo controlled trial of milameline, a muscarinic receptor agonist. The therapeutic trial itself become not achieved as a result of projected lack of efficacy on intervening time analysis; despite the fact, the MRI arm of the analyze changed into endured. Of the 362 topics who underwent a baseline MRI analyze, 192 topics underwent a second MRI one-year later. Hippocampal volume and temporal horn quantity have been measured from the MRI scans.

outcomes

The annualized % trade in hippocampal quantity (−four.9%) and temporal horn quantity (sixteen.1%) in the analyze sufferers had been in step with statistics from prior single web site experiences. Correlations between the rate of MRI volumetric trade and alter in behavioral/cognitive measures were stronger for the temporal horn than for the hippocampus. Decline over time changed into greater constantly viewed with imaging measures, 99% of the time for the hippocampus, than behavioral/cognitive measures (p<0.001). more advantageous consistency in MRI than behavioral/medical measures resulted in markedly reduce estimated pattern size necessities for clinical trials. The estimated variety of topics per arm required to discover a 50% reduction within the fee of decline over twelve months are: ADAS-Cog 320; MMSE 241; hippocampal volume 21; temporal horn extent fifty-4.

Conclusion

The consistency of MRI measurements obtained across sites, and the consistency between the multi-web page milameline records and that bought in prior single web site reports, exhibit the technical feasibility of the use of structural MRI measures as a surrogate conclusion point of disease development in therapeutic trials. besides the fact that children, validation of imaging as a biomarker of therapeutic efficacy in ad still awaits a positive trial.

The fundamental result measurements for therapeutic trials in Alzheimer's disease (advert) patients are behavioral or cognitive. as a result of the inherent look at various-retest variability in such measurements although, alternate options were sought. Magnetic resonance imaging (MRI) measurements of prices of entire mind or hippocampal atrophy had been, and are at the moment getting used as influence measures in several therapeutic trials for advert. although imaging has been utilized in medical trials on advert and vascular sickness for diagnostic functions, to our knowledge, no publication has regarded describing the MRI consequences of a therapeutic trial wherein structural MRI turned into used as an outcomes measure. MRI measures had been introduced to this trial to profit a claim for results on disease development as adverse to just symptomatic medicine in those situations the place medication impact was shown on the behavioral/cognitive measures 1-7.

We document the MRI results of a therapeutic trial of milameline, a centrally energetic muscarinic agonist. The therapeutic goal turned into augmentation of the diminished cholinergic characteristic attribute in ad eight,9. The therapeutic trial was no longer completed as a result of a projected lack of efficacy on meantime analysis. besides the fact that children, the MRI arm of the analyze was persevered to be able to bring together records for reference purposes. The aim of this manuscript therefore is not to report on the scientific outcome of the therapeutic trial itself, but fairly the MRI component of the trial to be able to illuminate methodologic issues, doc feasibility, and function a tenet for future experiences the use of MRI as an result measure. Demonstrating that the MR graphic records obtained in this trial from numerous sites have been each internally consistent and in line with reviews in prior single web site reports, we trust documents the technical feasibility of the use of MRI as an outcome measure of ailment development in therapeutic trials for neurodegenerative illnesses.

strategies look at Design

The study COG-320 become a fifty two-week randomized double blind placebo controlled parallel neighborhood multicenter trial of milameline, a muscarinic receptor agonist. All sufferers were titrated as much as the highest tolerated every day dose with a ceiling of 4mg/day. medical followup was at months one, three, six, and twelve. The primary outcomes measure was the Alzheimer's ailment assessment Scale-Cognitive sub-scale (ADAS-Cog). a couple of secondary effect measures were employed including the Mini-intellectual State examination (MMSE), world Deterioration Scale (GDS), and MRI measurements of the fees of atrophy of the hippocampi, and the fees of enlargement of the temporal horns10.

sufferers

All patients had probably ad of mild to moderate severity and were stronger than 50 years historic. MMSE ratings have been 10-27, inclusive. sufferers have been excluded for evidence of great cerebral vascular sickness, non-ad dementia, essential psychiatric problems, major or unstable scientific situations, seizure ailment, Parkinson's sickness, substance abuse, principal head trauma, or tumor.

planned enrollment turned into a complete of 450 topics; all from US websites with a normal of ten topics (latitude 10-15 highest) from each of 45 websites. The planned look at duration became from June 1996 to December 1998.

MRI

so as to keep away from difficulties linked to MRI company's proprietary information acquisition and storage protocols, handiest these websites with a regular electric MR Imager have been asked to sign up sufferers in the MRI element of the trial. The genuine hardware and utility configuration of scanners at diverse sites distinctive. All scanners had been 1.5T aside from a single web page at 0.5T.

The particular person imaging sequences in the examination protocol were:

A sagittal T1-weighted scan with contiguous 5-mm slices.

A 3D volumetric spoiled gradient recalled echo (SPGR) scan got within the coronal plane with minimum full echo-time, minimal repetition time, 124 partitions, and 1.6 mm partition thickness.

A T2-weighted scan become acquired for pathology screening functions.

every site went via an preliminary qualifying part ahead of scanning sufferers for the trial. The qualifying part had two accessories. First, each site was required to function the heart beat sequences distinct for the imaging protocol, film the examination, and send the films to the principal analysis web site on the Mayo health center. the pulse sequence parameters have been checked at the important analysis web site to insure that each collaborating website could execute the targeted imaging sequences as it should be. second, the scanner on which study COG-320 patients could be imaged at each and every web site underwent a top quality manage comparison. with a purpose to start study COG-320ing sufferers, sign to noise ratio (SNR) and geometric distortion analyses ought to had been achieved and evaluated at the relevant web site, and should have fallen inside predetermined necessities.

SNR and geometric distortion measurements had been made on the designated scanner at every site both throughout the qualification part, and all through the trial on a monthly groundwork. every web page carried out and submitted to the crucial image analysis web page an axial spin echo and sagittal, coronal, and axial gradient echo acquisitions that have been especially designed to consider SNR and geometric distortion. The fine manage (QC) imaging protocol changed into about 15 minutes in duration, and become finished with a standardized QC phantom provided through the brand. The phantom contained spatially uniform regions where SNR measurements have been got and additionally contained fiducial markers which have been used to examine geometric distortion11. The statistics from the QC MR protocol turned into transmitted to Mayo, where an ongoing checklist of SNR, image artifacts, RF energy, and geometric distortion along all three axes turned into kept for each scanner all the way through the period of the trial.

All graphic facts (each sufferers’ imaging statistics and phantom QC imaging records) become sent with the aid of both tape or disc to Mayo and archived electronically. For each and every affected person the entire intracranial volume changed into measured from the sagittal T1 sequence. The volumes of the appropriate and left hippocampi and temporal horns were measured in line with in the past described criteria 6,12,13 on the 3D SPGR sequence. the entire measurements were accomplished at Mayo through a single individual over two years. Intra-rater co-productive of version for serial hippocampal measurements has been documented at 0.28% 6. The particular person performing the MR graphic analyses was blinded to all scientific tips including the middle and the scan date – ie whether each and every scan turned into the 1st or 2nd in the pair. The order of first and 2d scans changed into randomized.

MRI statistics analysis changes of uncooked Hippocampal extent for complete Intracranial quantity

The uncooked hippocampal volumes in each and every area were adjusted first via complete intracranial quantity (TIV) after which 2d by using referencing the TIV adjusted uncooked hippocampal extent in that area to age and gender particular percentile values in a normal aged population13. Hippocampal volumes in cognitively ordinary topics vary with head size, (individuals with higher TIV have bigger hippocampi) and age (quantity declines with advancing age).

in order to identify the connection between hippocampal extent and TIV in normals, free of the effect of growing old, the sagittal T1 and coronal 3D SPGR pulse sequences had been carried out in seventy nine younger topics between the age of 17 and forty five, who had been documented to be free of neurologic sickness. the relationship between hippocampus and TIV in these commonplace young individuals changed into deduced the use of a regression evaluation of hippocampus on TIV. The regression equations describing anticipated hippocampal volume as a characteristic of measured TIV was derived one after the other for men and women and are:
the place H = uncooked unadjusted hippocampal quantity, and H’ = hippocampal quantity adjusted via TIV. From this statistics in young individuals we're able to assignment what the quantity of the hippocampi should still be for a given TIV in anybody unaffected by way of getting older.
Age and Gender particular aged Norms for TIV Adjusted Hippocampal extent

We next turned to hippocampal volumes in standard elderly people. The sagittal and 3D SPGR pulse sequence had been carried out in 181 usual elderly people (sixty one men and a hundred and twenty women, suggest age eighty.four years, latitude 62-a hundred years) as part of the continued scientific research protocols within the Mayo medical institution Alzheimer's disease research core (ADRC) and Alzheimer's sickness affected person Registry (ADPR). For each and every of those standard elderly topics the TIV adjusted hippocampal volume become computed in keeping with the relationship between TIV and hippocampal volume that had been derived for the usual younger cohort as described above. Age and gender certain normative percentiles of this TIV adjusted hippocampal extent cost were then computed for the regular aged cohort. The formulation for computing age and gender certain normative percentiles for hippocampal volume changed into identical to the method we now have in the past described 13, apart from that here normative percentiles had been calculated in the elderly topics for the TIV adjusted hippocampal extent.

Age and TIV Adjusted Hippocampal quantity in Milameline study COG-320 patients

The baseline hippocampal volumes in the advert circumstances within the milameline analyze had been expressed as W rankings, as we now have finished prior to now 13. The W ranking corresponds to the percentile price in a typical standard distribution. A W ranking of zero corresponds to the fiftieth percentile of standard elderly individuals. A W rating of 1.645 corresponds to the 95th percentile of ordinary elderly individuals, and a W score of −1.645 corresponds to the 5th percentile.

Serial MRI Measures in Milameline analyze sufferers

In every study COG-320 affected person quantity measurements of the hippocampi have been acquired at two diverse time elements. From these, the raw exchange in quantity (in mm3), uncooked annualized change in mm3/yr, and annualized percent alternate have been calculated. No relationship turned into discovered between TIV and the rates of trade in hippocampal volume, and therefore no TIV adjustment became needed6.

We didn't have measurements of temporal horn quantity attainable in young normals, or old commonplace subjects. because of this, adjustment of temporal horn volume for TIV, and the W score components could not be developed for the temporal horn measurements. We analyzed the annualized raw volumetric exchange, and the annualized p.c change in temporal horn extent in a way just like that described for the hippocampus.

Statistical evaluation

The variables of hobby within the analyses were age, gender, training, ADAS-Cog score, MMSE, GDS, and MRI volume variables. The MRI volume variables encompass raw facts in mm3 for the appropriate, left, and total hippocampus at baseline, W rating of complete hippocampal volume at baseline, exchange in complete hippocampal quantity, uncooked baseline temporal horn volumes, and change in complete temporal horn quantity. Rank sum checks had been used for skewed statistics, and two sample t exams had been used for continually distributed information. Spearman correlation became used to test for associations between MRI volume measurements and behavioral/cognitive measures, training, gender, and age. Univariate and multivariate modeling were used to check for associations between baseline MRI volumes and both demographic and behavioral/cognitive measures. Univariate and multivariate modeling had been used to check for associations between change in MRI volumes and baseline MRI extent, demographic, and behavioral/cognitive measures. Rank transformations were used for all records within the multivariate modeling. one way ANOVA was used to test for differences in baseline hippocampal W rating between the distinctive facilities. The diploma to which serial measures, imaging and behavioral/cognitive, declined perpetually over time changed into compared the usage of the sign test.

pattern size calculations for scientific trials

because of the advantage hobby in the usage of structural MRI as a biomarker of disorder progression in scientific ad trials, we carried out pattern size calculations to become aware of medicine effect in response to the annual alternate records in MMSE, ADAS-Cog, hippocampus, and temporal horn (the GDS changed into felt not to be a competitive metric). pattern measurement calculations were in response to the belief of a 50% medication effect over three hundred and sixty five days—i.e. a 50% discount within the exchange over 365 days in a handled vs. a placebo neighborhood. tests had been one sided with vigour set at 90%.

consequences Baseline Demographic, Behavioral/Cognitive, and MRI facts

Out of 453 topics enrolled within the drug trial, 362 participated in the MRI component. evaluation of baseline facts is limited to those topics (). amongst these 362 subjects, 188 had been randomized to treatment and 174 to placebo. No ameliorations in gender distribution (roughly 60% feminine), schooling, behavioral/cognitive measures, or baseline MRI extent measures were existing between the treated and placebo businesses.

Baseline Demographic, Cognitive, and MRI facts by means of treatment community

ladies had much less schooling, (p =0.001) and worse baseline cognitive efficiency on the ADAS-Cog (p =0.02) and MMSE (p = 0.01). The raw appropriate, left, and total hippocampal (p<0.001) and temporal horn (p <0.001) volumes have been larger in men than ladies. There changed into a trend toward more suitable hippocampal atrophy (lower W rating and typical percentile rating) in women than guys, but this did not attain value.

The correct hippocampus become approximately a hundred-200 mm3 (roughly 5%) better than the left in each treated and placebo businesses. besides the fact that children, no right-left transformations were current in any of the correlations between hippocampal or temporal horn volume and baseline demographic or behavioral/cognitive measures, nor had been correct-left differences current in correlations between exchange in MRI volumes and change in behavioral/cognitive measures. therefore, all subsequent analyses of MRI extent measures are said for the overall (sum of correct plus left) quantity instead of appropriate or left volumes one after the other.

Correlation among Baseline Hippocampal quantity, Demographic, and Behavioral/Cognitive Measures

The placebo and handled companies have been mixed for baseline correlation analyses since the baseline MRI and behavioral/cognitive measures had been completed earlier than medication initiation. Univariate correlations between baseline hippocampal W score, age, gender, training, ADAS-Cog, MMSE and GDS had been carried out. No colossal correlations had been existing except for that between hippocampal W score and age (r = 0.15, p = 0.004). A collection of multivariate fashions had been constructed with efficiency on the behavioral/cognitive measures listed above as the stylish variable, and baseline hippocampal W ranking, age, gender, and schooling as unbiased variables. none of the partial correlations between baseline hippocampal W ranking and baseline behavioral/cognitive performance had been gigantic.

Normative temporal horn measurements have been now not available and consequently a equipment for adjusting raw baseline temporal horn volumes of milameline analyze sufferers for age and gender in normals changed into not feasible. We hence did not examine correlations amongst baseline temporal horn extent, demographic, and behavioral/cognitive measures.

changes from Baseline

All analyses of change (change in MRI volumes and alter in behavioral/cognitive scores) are in response to the 192 topics who had both a baseline and a second MRI scan (). No difference in annual exchange was existing between the handled and placebo businesses in any of the behavioral/cognitive measures, nor for both of the MRI quantity variables. For each of those variables, despite the fact, the median annualized alternate changed into distinctive from 0 (p < 0.001, for all, signed rank examine). in addition, all variables in changed within the anticipated path over time – ie. behavioral/cognitive efficiency worsened, hippocampal volume decreased, and temporal extent extended.

Annual trade from Baseline in Behavioral/Cognitive and MRI Variables

To assess how invariably imaging and behavioral/cognitive measures declined over time, we computed the share of individuals in whom the measures in declined. Decline become defined as a decrease in hippocampal extent, a rise in temporal horn quantity, a lower in MMSE score, and an increase in the GDS and ADAS-Cog ratings. The volume of the hippocampus reduced in 99% of subjects whereas most effective 60.4% of topics ADAS-Cog and 66.2% of topics’ MMSE scores declined. In pair-wise comparisons, the percentage of decliners become more desirable for the hippocampus than any of the behavioral/cognitive measures or the temporal horn (p<0.001). The percentage of decliners changed into additionally better for the temporal horn (eighty five.four%) than for any of the behavioral/cognitive measures (p <0.001).

pattern measurement calculations for scientific trials

there were two outliers in the MMSE statistics. After deleting these values for functions of computing sample size requirements, the MMSE and temporal horn statistics have been not incredibly skewed and transformations of these information had been no longer obligatory. For these variables, we computed the effect size to be 50% of the observed mean annual expense. The hippocampus and ADAS-cog were particularly skewed and transformations of these facts have been needed. For these we computed the impact dimension after transformation as follows: converted(median) - converted(.5xmedian).

For ADAS-cog, we first changed to Y’ = Y− min+1 (min = −fifty nine.9), then used Y’*10−2, the place “min” refers back to the minimum accompanied cost.

For hippocampus, Y’ is defined as above (min = −15.2), and we used Y’*102.

note that we are the usage of a 50% reduction in mean rate of alternate the place transformations aren't required and a 50% discount within the median rate of alternate the place transformations are required. After deletion of both outliers from the MMSE records, the imply annual percent trade turned into 10.7% (19.9). The sample size required to discover a 50% discount during this fee of exchange in a 12 months placebo managed trial with vigor of ninety% (one-sided t verify on the .05 level) is 241 per arm. For ADAS-Cognitive, the statistics were incredibly skewed with a median of 16.4% (the linked SD of the converted information became sixty five.4). in an effort to become aware of of 50% discount, N=320 per arm are crucial. For the hippocampus, the records had been once again extremely skewed with a median of −4.9% (the linked SD of the changed records become 2.1). in order to detect a 50% reduction, N=21 per arm are essential. The information for the temporal horn had been now not skewed, with mean sixteen.1% (SD14.1), and N=fifty four per arm are crucial.

factors that have an impact on alternate in MRI extent

in an effort to examine whether demographic variables or baseline MRI quantity influenced the annualized trade in extent, a multivariate model changed into constructed with the raw annualized change in hippocampal volume (mm3) because the elegant variable, and with age, gender, schooling, and baseline hippocampal W rating as unbiased variables. The slope (Beta), standard error, partial Spearman's correlation, and associated p cost for each of the four unbiased variables during this mannequin seem in . Baseline hippocampal W ratings have been inversely associated with prices of hippocampal atrophy (ie smaller hippocampi at baseline had been linked to enhanced quantity loss over time). Age, gender, and schooling at baseline were no longer associated with the annualized rate of hippocampal atrophy.

factors That impact exchange in MRI Volumes

similar modeling became carried out the use of the uncooked annualized alternate in temporal horn extent (mm3) because the dependent variable, and age, gender, training, and baseline temporal horn quantity as predictor variables. as a result of W ratings had been not purchasable for temporal horn measurements, the uncooked temporal horn quantity in mm3 at baseline become used as the unbiased baseline extent variable. more youthful age at baseline became associated with a greater annualized exchange in temporal horn volume (i.e., a superior price of atrophy). a bigger temporal horn extent at baseline become additionally linked to a larger annualized trade in temporal horn quantity.

similar modeling changed into carried out the usage of the raw annualized exchange in quantity (hippocampal and temporal horn) as the based variable, and age, gender, education, and baseline behavioral/cognitive variables as predictor variables. not one of the baseline behavioral/cognitive variables had been associated with the annualized exchange in hippocampal extent. ADAS-Cog became the only baseline cognitive variable linked to the annualized change in temporal horn volume (r = 0.38, p<0.001).

Correlation between MRI Volumes and change in Behavioral/Cognitive Measures Univariate Analyses

To investigate the association between trade in behavioral/cognitive efficiency and baseline hippocampal and temporal horn extent, univariate analyses were carried out with the annual percent alternate in every of the three behavioral/cognitive measures as dependent variables and each baseline MR structure's extent as the impartial variable. With one exception (MMSE exchange rating and baseline temporal horn volume) none of these correlations were huge ( and ).

Correlation Between Annual percent exchange In Behavioral/Cognitive Variables and Hippocampal extent change
Correlation Between Annual % alternate in Behavioral/Cognitive Variables and Temporal Horn volume alternate

To check the affiliation between exchange in behavioral/cognitive performance and alter in hippocampal volume or temporal horn quantity over the equal time duration, a series of univariate analyses had been performed with the annualized p.c exchange in each of the behavioral/cognitive measures as based variables, and the annualized raw alternate in MR extent (mm3) as the unbiased variables. None of those correlations were giant for hippocampal extent. alternate in all three cognitive variables turned into associated with the annual uncooked alternate of temporal horn extent ( and ).

Multivariate Analyses

Multivariate models had been then developed, one for each and every of the three behavioral/cognitive variables. In each and every mannequin, the annualized p.c alternate in behavioral/cognitive performance become the dependent variable, and the independent variables were age, gender, training, MRI quantity at baseline, and the annualized uncooked alternate in MRI extent (mm3). For baseline volumes, simplest baseline hippocampal W rating become big and best with trade scores on the GDS.

In multi-variate modeling, enhanced annualized trade in temporal horn extent (i.e. stronger price of atrophy) changed into associated with a more advantageous trade (worse cognitive performance) on all three behavioral/cognitive measures. In distinction, annualized exchange in hippocampal volume become not linked to exchange scores of any of the cognitive behavioral measures.

MRI best manage Measures

All 38 collaborating sites eventually met qualifying standards from the standpoint of MRI fine control. despite the fact, over the direction of the look at, effects of QC analysis warranted site contact 19 times. most of the QC alerts took place all through the one-month qualifying phase, which preceded genuine enrollment of patients. the nature of the QC signals have been: gradient coil error (i.e., geometric distortion), nine alerts at seven sites; low SNR, five signals at four websites; noise strains, three indicators at three websites; other, two alerts at two sites.

yet another measure of first-rate manage is the consistency of measured volumes throughout sites. The mean hippocampal W rating throughout all sites changed into −1.seventy eight (SD 0.ninety seven). Hippocampal W rating did range amongst websites (a method ANOVA, p = 0.04). We then used the pupil-Newman-Keuls distinctive range check to do pairwise comparisons, and no pairwise difference between websites became found. We estimated the add-ons of variance: variance coming up from change among sites (VA) and variance coming up from change amongst patients within websites (VW). there were VA − 0.04 and VW − 0.90, and the % of total variance (VT = VA + VW) as a result of variability amongst sites changed into four.seventy one% (VA/VT*one hundred%). Stepping down multivariate regression become used with hippocampal W score as the dependent variable; age at MRI scan, female gender, medicine, site, baseline ADAS-Cog rating, baseline MMSE rating, and baseline GDS score because the independent variables. only 1 web page was enormously distinct from the others during this analysis.

dialogue

an important aim of these analyses became to validate the technical feasibility of using MRI as an influence measure of disorder progression in multi-web page reports of neurodegenerative disease. One measure of the validity of multicenter facts, is the diploma to which it is concordant with equivalent facts got from a single core or centers. Single center records is less likely to be corrupted by means of technical non-uniformity than multicenter statistics. in the milameline analyze patients, the appropriate hippocampus turned into roughly 5% greater than the left. This identical facet to aspect volume difference has been found many times in analyses of normals and patient groups during the age spectrum by means of our group and others and is a mirrored image of general right-left asymmetry in hippocampal extent 12,14-20. The uncooked hippocampal and temporal horn volumes within the milameline sufferers are in close agreement with these values suggested up to now in ad subjects from our personal middle 12,13. The standard hippocampal W score and corresponding percentile rating of the milameline look at patients, third percentile of commonplace controls, corresponds very carefully to the published W rankings of light to moderately demented advert sufferers in our own core 13.

The observed inverse correlation between uncooked hippocampal extent and age is in keeping with our personal facts and that of others for each advert patients and normals1,5,12,13,21,22. We interpret the decline in hippocampal W rating with advancing age as an impact of disease length. greater age should on usual correspond to more suitable sickness period that in turn will correspond to smaller (more atrophic) hippocampi. The adjustment for age in computing the W rating correction handiest accounts for the effect of commonplace getting old on hippocampal extent. It doesn't account for the impact of more suitable disorder length in older advert sufferers (vs younger ad sufferers). The proven fact that no correlations have been observed between baseline hippocampal extent and international behavioral/cognitive examine efficiency in the milameline look at topics might also initially seem to be counter intuitive. youngsters, here's in line with our previous event when radiologic-cognitive correlations are constrained to a single medical neighborhood - as an example advert sufferers simplest or ordinary topics only. We believe that the inability of correlation during this circumstance is as a result of the truncated range of values for both baseline hippocampal quantity and cognitive performance. In past reports, when normals were mixed with advert topics, thereby expanding the range of quantity and cognitive efficiency values, tremendously significant correlations have been current 23.

As indicated in , no treatment impact of milameline turned into accompanied in the MRI statistics. This become an anticipated discovering as a result of the lack of treatment efficacy accompanied on period in-between analysis and sufferers randomized to medication had discontinued the drug earlier than completing the entire 12-month course when the 2nd MRI become acquired. The annualized rates of hippocampal atrophy in the ad subjects in this trial on ordinary had been just beneath 5%. here's just a little greater than the annualized fees of hippocampal atrophy followed in our own neighborhood/referral advert patients that had been just under 4%6,7. One believable cause of this moderate change is that our group/referral based ad sufferers regular around eighty years of age, whereas the standard age within the milameline analyze turned into 74 years. It may well be that a younger group of advert sufferers have a just a little extra aggressive medical course, and hence a a little improved cost of atrophy.

it is going to be referred to that monstrous overlap in atrophy fees exists between advert sufferers in the milameline look at and cognitively normal aged topics from our own core 6. The latitude of annualized % alternate rates in our common topics was −four.8% to 0.2% for hippocampus, and −7.7% to 26.3% for temporal horn 6. the usage of these values, 90/192 (forty seven%) of the milameline advert sufferers’ hippocampal quotes and 142/192 (seventy four%) of the milameline ad sufferers’ temporal horn fees overlapped into the regular latitude.

The behavioral/cognitive and MRI measures in all modified within the expected route over time. it really is, as behavioral/cognitive efficiency worsened, hippocampal quantity declined, and temporal horn quantity elevated. besides the fact that children, decline turned into much greater constantly viewed with imaging, specifically the hippocampus, than with behavioral/cognitive measures. definitely whereas ninety nine% of subjects showed the anticipated decline in hippocampal volume over time, simplest 60% worsened on the ADAS-Cog and sixty six% on the MMSE and most effective 39% on the GDS. consistent consequences and high verify re-check reproducibility are desirable traits for an outcome measure in therapeutic trials, given that the measure is delicate to the biologic points of activity. since the drug trial itself became now not completed, these facts don't handle no matter if MRI measures are stronger or worse than regular cognitive/behavioral measures as an influence metric in therapeutic trials. besides the fact that children, these records do display that MRI measures greater at all times comply with the anticipated decline because of sickness development, than standard behavioral/cognitive measures obtained within the identical group of subjects over the same duration of time.

Assuming a standard common of a 50% reduction within the fee of decline over 12 months for all measures, the impact size calculations point out that sample dimension required for scientific trials should still be extensively smaller for the MRI measures vs these commonly used clinical/psychometric measures. In apply, attrition would need to be developed into sample size estimates, which we didn't do in these calculations. additionally, one might argue that the annual price of decline accompanied for every individual measure in cognitively normal aged subjects should still be subtracted from the rate in ad patients with a view to assess the fee of alternate due notably to ailment progression and hence “attainable for therapeutic change”. We did not build this into the impact size calculations either. finally, the analyses were in accordance with a 50% reduction within the fee of decline over one year, which may well be excessively confident. youngsters, the goal of the analysis was to evaluate the measures head-to-head using a typical standards in the identical community of patents, and in these information, the MRI measures outperformed the clinical/psychometric measures.

Smaller baseline hippocampal volume become linked to a improved price of hippocampal atrophy. Older age changed into associated with a more advantageous price of temporal horn enlargement. however, the magnitude of each of those relationships became handiest modest, with slopes of −0.15 and −0.19. the most amazing relationship in the analyses in took place between baseline temporal horn extent and the expense of temporal horn expansion. larger temporal horn volume at baseline was linked to a superior price of temporal horn expansion, and the magnitude of this relationship turned into gigantic with a slope of 0.53. It is not clear why patients with better atrophy at baseline confirmed enhanced rates of atrophy over the direction of the study COG-320, but it might be that baseline temporal horn quantity is a trademark of these patients who've extra aggressive pathologic development.

The absence of consistent correlation between the trade in behavioral/cognitive measures and alter in hippocampal quantity changed into sudden (). We anticipated to locate a powerful correlation between worsening cognitive performance and superior prices of hippocampal atrophy. One reason behind a failure to study COG-320 this kind of correlation, other than noise within the statistics itself, rests with truncation of the latitude of values in each charges of hippocampal atrophy and in quotes of trade in cognitive performance in these uniformly selected advert sufferers. It could even be authentic that in sufferers with based advert, the most gigantic pathologic sickness progression happens outside the hippocampus, and for this reason hippocampal change measurements and cognitive/behavioral trade are easily not strongly correlated. this suggests that dissimilar measures should still be evaluated in future clinical trials, as the suggestions supplied by using diverse imaging measures may well be orthogonal to each one more.

on the outset, the principal emphasis became on hippocampal volume with temporal horn extent representing a secondary MRI measure. An sudden outcomes, therefore, become that basic correlations between alternate in cognitive performance and alter in MRI volume have been improved with the temporal horn than with the hippocampus (). however modest in magnitude with slopes lower than 0.30, correlations had been existing between rate of temporal horn enlargement and all behavioral/cognitive measures (). all of the correlations had been in the anticipated path, it is greater charges of temporal horn enlargement corresponded to greater charges of behavioral/cognitive decline. apparently, giant correlations have been most effective current in the multivariate models, which managed for age, gender, training, and baseline temporal horn extent. here's logical, as alternate in temporal horn extent become particularly associated with baseline temporal horn volume (). One viable explanation for this discrepancy between accompanied correlations with the hippocampus vs the temporal horn, is that of both measures, the temporal horn should still be extra sensitive to cerebral atrophy backyard the medial temporal lobe24. Temporal horn growth occurs no longer just with atrophy of the hippocampus however additionally as a reflection of atrophy in different medial temporal lobe limbic areas just like the entorhinal cortex as neatly because the last temporal lobe including neocortical association areas. seeing that all patients during this look at had been within the light to moderate section of advert, all doubtless had pathologic involvement that prolonged neatly beyond the hippocampus.

12 months temporal horn enlargement
Annual change in ADAS-Cog vs. temporal horn

regardless of established ongoing quality control classes at each of the collaborating sites, 19 indicators have been triggered by using undetected QC problems 11. We conclude from this event that centrally orchestrated MRI QC surveillance is each possible and imperative in a multi-site trial using MRI as outcome measure.

We compared baseline hippocampal W scores across centers to examine the consistency of statistics acquire from numerous websites. The proven fact that just one outlier changed into identified when comparing baseline W scores across facilities, illustrates that MR information will also be got at multiple websites and analyzed centrally without obvious systematic blunders.

Most posted MRI studies were derived from a single institution. We don't seem to be aware about any publications that have validated the feasibility of multi-website acquisition and imperative analysis of structural MRI facts as an result measure in an ad therapeutic trial. there are lots of causes to suspect a priori that mult-website MRI data might no longer be internally consistent -- ameliorations in scanner hardware, application, scanner QC maintenance courses, and so forth. We trust the statistics supplied in this paper validates the technical feasibility of the usage of MRI as an outcomes measure of disorder progression in multi-middle ad therapeutic trials. This look at does not, however, show that imaging measures represent valid biomarkers of therapeutic efficacy. this could require a favorable therapeutic trial that has included serial imaging measures in the examine design.

Acknowledgments

Supported by Parke-Davis Corp.

Appendix: examine members

1. Geoffrey Ahern, M.D., Ph.D. The university of Arizona Tucson, AZ 85724-5023

2. Fred Allen, M.D. Carolina Neurological sanatorium, PA Charlotte, NC 28203

3. Piero Antuono, M.D. Froedtert Memorial Lutheran medical institution Milwaukee, WI 53226-3522

4. Jeff Apter, M.D. Princeton Biomedical analysis, PA

5. Stephen Asher, M.D. Anderson Plaza medical constructing Boise, id 83702-6130

6. Nancy Barbas, M.D. school of Michigan medical center Ann Arbor, MI 48109-0005

7. James Burke, M.D., Ph.D. Duke university clinical middle Durham, NC 27710-0001

eight. Gastone Celesia, M.D. Loyola tuition medical center

9. David J. Coffey, M.D. Dartmouth-Hitchcock clinical core

10. Cal Cohn, M.D. The Cohn center Psychiatry Houston, TX 77074

11. Kirk R. Daffner, M.D. Reisa Sperling, M.D. Brigham Behavioral Neurology neighborhood

12. Alan Dengiz, M.D. St. Joseph Mercy Hopsital Ann Arbor, MI 48106

13. David Drachman, M.D. tuition of Massachusetts scientific faculty

14. Barry Gordon, M.D., Ph.D. Johns Hopkins tuition

15. Neill Graff-Radford, M.D. Mayo health facility-Jacksonville

sixteen. Linda Hershey, M.D. BVAMC Buffalo, new york 14215

17. Marc Hertzman, M.D. Crain Towers Glen Burnie, MD 21061

18. Mustafa Husain, M.D. Southwestern scientific core Dallas, TX 75235-9070

19. William Jagust, M.D. UC Davis clinical middle

20. Jeffrey Kaye, M.D. Oregon health Sciences college

21. Arifulla Khan, M.D. Northwest clinical analysis center Kirland, WA 98034

22. Ranga Krishnan, M.D. Duke college clinical core

23. Dennis McMannus, M.D. SIU college of medicine Springfield, IL 62794-1413

24. Jacob Mintzer, M.D. scientific institution of South Carolina Charleston, South Carolina 29425-0742

25. Jorg Pahl, M.D. Pahl brain friends, P.C. Oklahoma city, adequate 73120

26. Murray Rosenthal, DO Behavioral medication materials San Diego, CA 92123

27. Carl Sadowsky, M.D. Palm beach Neurological group West Palm beach, FL 33407-2441

28. Frederick Schaerf, M.D. feet. Meyers, FL 33907

29. Douglas Scharre, M.D. Ohio State institution Columbus, OH 43210

30. Rachel Schindler, MD Pfizer Inc. long island, big apple 10017

31. Joshua Shua-Haim, M.D. Monmouth scientific core lengthy department, N 07740

32. Paul Soloman, Ph.D. memory problems hospital Bennington, VT 05201

33. Steven Targum, M.D. CNS Philadelphia Philadelphia, PA 19106

34. Christopher Van Dyck, M.D. Yale tuition school of drugs

35. Troy Williams, M.D. Peoria, AZ 85381

36. William Pendlebury, M.D. tuition of Vermont

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Investigation of grime Storms getting into Western Iran the usage of Remotely Sensed facts and Synoptic evaluation465 viewed in figure 9C and 9D, cyclonic and anti-cyclonic cir-
466 culations are fashioned respectively under the front and
467 again of trough. right through dusty days of the western and
468 south western Iraq, a trough lies at 500 hPa level which
469 leads to the formation of cyclonic (low drive) and
470 anti-cyclonic (excessive pressure) circulations in Iran and
471 jap shores of the Mediterranean sea. basically, the filth
472 supply is strengthened through being located between low and
473 excessive-pressure centres and due to this fact, being affected
474 via pre-bloodless front (bloodless sector), west–east, excessive-
475 speed winds. while trough receives deeper, cyclonic circula-
476 tion relocates towards reduce latitudes on Saudi Arabia. In
477 these cases, speedy winds causing huge dust storms
478 will kind in heat sector of the cyclone with a roughly
479 south–north direction.
480 Conclusion
481 The latest analysis makes use of numerous facts and strategies to
482 determine the origin of the grime storms affecting the west-
483 ern Iran. by way of analysing the corresponding satellite tv for pc photographs,
484 three main paths of dust paths were identified:
485 –direction 1: the northwest-southeast direction, from the
486 north-western Iraq and the south japanese Syria,
487 to western Iran,
488 –direction 2: the second pathway with jap-western
489 direction, from Iraq-Jordan borders prolonged
490 to the western Iran,
491 –direction three: the final direction from southern banks
492 of Persian Gulf to western Iran via a
493 south–north directing.
494 The function of the first course in the mobility of dirt parti-
495 cles to the western Iran is a whole lot extra giant than
496 other two paths. The temporal distribution of western
497 Iran dust movements suggests that the primary grime route and its
498 grime source have been activated from 2005 and
499 hit a top in 2008. therefore, this course and its grime-
500 inclined regions may also be regarded because the leading foundation of
501 fresh filth storms coming into western Iran. grime events in
502 paths one and two don't show enormous upward push in contemporary
503 years. dust movements relocated from northwest-southeast
504 direction in particular occur within the heat periods of the year. In
505 distinction, the paths of two and three have highest sea-
506 sonal actions in the cold months. The latest research
507 has used soil guidance, the type of land covers,
508 and wind speed and path of sea level drive
509 to find the grime sources extra exactly. Analysing theses
510 advice, we discovered four main grime-inclined areas
511 which affect western Iran:
512 –supply 1: the jap banks of Euphrates and the
513 western banks of Tigris as leading western Iran
514 filth sources,
515–source 2: the western and south western Iraq, and
516also small components of Syria and Jordan,
517–supply three: the japanese and south-eastern deserts of
518Arabia called Rub-Al-Khali wasteland,
519–supply four: the south-eastern Iraq, as a secondary supply.
520The examination of the atmospheric situations gov-
521erning each and every dirt supply shows that synoptic patterns
522during dirt routine originating from source one have
523been specifically littered with the surface diabatic approaches.
524Whereas, filth storm in sources two and three are
525caused by way of cyclonic and anti-cyclonic circulations and are
526largely outcomes of dynamic approaches of westerly winds.
527Endnotes
528
a
reasonable resolution Imaging Spectroradiometer.
529
b
Brightness Temperature difference.
530
c
Q1http://rapidfire.sci.gsfc.nasa.gov/realtime.
531
d
Q2www.esa.int/due/ionia/globcover.
532
e
Temperature anomaly = (each day temperature –regular
533daily temperature).
534Competing interests
535The authors declare that they have no competing pastimes.
536Authors’contributions
537The most materials of this study COG-320 including: research scheme, data evaluation, and
538manuscript instruction were applied by means of first two authors. Third author
539has helped to locate an effective filth detection algorithm and make it
540convenient with the aid of programing in MATLAB software. other authors have
541accompanied in editing, cohesion and translating presented paper.
542All authors read COG-320 and permitted the remaining manuscript.
543Acknowledgements
544This analysis paper is made possible in the course of the help and economic aid
545from science and know-how affairs of Islamic republic of Iran.
546Author details
547
1
department of far off Sensing & GIS & Geoinformatics analysis Institute
548(GRI), school of Tehran, Tehran, Iran.
2
Geoinformatics research Institute
549(GRI), tuition of Tehran and branch of Geography and Regional
550Research, college of Vienna, Vienna, Austria.
three
department of Soil Science,
551Tarbiat Modares school, Tehran, Iran.
4
school of electrical and laptop,
552Tarbiat Modares school, Tehran, Iran.
5
Geoinformatics research Institute
553(GRI), institution of Tehran, Tehran, Iran.
554Received: 12 February 2013 approved: 14 October 2014
555
556References
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557
Goudie AS, Middleton N: wilderness filth within the world gadget. ny:
558
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