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CLINICAL RESEARCH

European Heart Journal (2009) 30, 202–208
doi:10.1093/eurheartj/ehn452

Arrhythmia/electrophysiology

Changes of the corrected QT interval in healthy
boys and girls over day and night
Thomas Krasemann1,2*, Christina Strompen 1, Jasmin Blumenberg 1,3,
Josef Gehrmann 1, Gerhard Burkhardtsmaier 4, and Johannes Vogt 1
1
Department of Pediatric Cardiology, University Children’s Hospital Muenster, Albert-Schweitzer-Str. 33, D-48149 Muenster, Germany; 2Department of Pediatric Cardiology,
Evelina Children’s Hospital, Guy’s & St Thomas NHS Foundation Trust, Lambeth-Palace Road, London SE1 7EH, UK; 3Klinikum Minden, Kinderklinik, Portastraße 7-9, 32427 Minden,
Germany; and 4Institute of Biomedical Statistics, Westfalian Wilhelms-University Muenster, Albert-Schweitzer-Str. 33, D-48149 Muenster, Germany

Received 24 March 2007; revised 24 June 2008; accepted 18 September 2008; online publish-ahead-of-print 2 October 2008

Aims

The study was designed to detect changes in corrected QT intervals over day and night in both sexes in healthy
children.
.....................................................................................................................................................................................
Methods
The corrected QT interval was calculated from 24 h ECGs obtained from 282 healthy children aged 6 months to
and results
18 years. The QTc interval as measured by the 24 h recording differs to the standard ECG measurement which is
in average of 40 –50 ms shorter. The QTc interval changes little over a 24 h period and is remarkably constant
despite significant heart rate changes in healthy children.
.....................................................................................................................................................................................
Conclusion
The routine ECG—even if the calculated values differ markedly from those obtained over 24 h—seems to be a good
screening method for the measurement of corrected QT intervals, because the corrected QT interval is kept
constant over the whole day in healthy children.

----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords

QT-interval † 24-hour-ECG † Children

Introduction
More than 100 years ago, in 1903, William Eindhoven described
the electrocardiogram; and prolonged recordings were first
made almost 60 years later by Holter in 1961.1
It is now known that during growth from the neonate to the
adolescent, the size and position of the heart changes in relation
to the whole body as well as the right ventricular pressure.
Thus, the normal ECG of a small child might be considered to
be pathological in adulthood. It is therefore essential to have
normal values (or at least guide values) for each age group.
Davignon et al.,2 Garson,3 Stoermer and Heck,4 or Rijnbeck
et al. 5 performed several 1000 routine ECGs in healthy children
and published their normal values of the routine ECG.
Measurement of the QT interval is difficult even with high
quality electrocardiography. It is usually carried out in lead II to
avoid U waves. However, James cited in Garson3 stated 40 years
ago: ‘In electrocardiography there is no more nebulous measurement than the QT interval.’ The QT interval, however, is an
important measurement because QT prolongation is associated

with severe ventricular arrhythmias in the congenital and drug
induced long QT syndromes.
There are only very few studies on QT interval in children out of
the neonatal age where measurements are particularly difficult to
interpret, for example the one conducted by Eberle et al.6 Their
youngest child was 5.2 years and their oldest 16.5 years. They
only looked at the QT interval on the routine ECG, but did not
perform a 24 h study. The very few Holter ECG studies on children focus on the heart rate.7 – 11 Until now, there has been no
data on the QT interval in children at different times of the 24 h
cycle, which have been shown in adults.12,13
In 1920, Bazett14 corrected the QT interval to make it in different heart rates comparable. Several formulas have been developed
since then,15 – 18 but worldwide the commonest in use is still
Bazett’s formula. Interestingly, in comparison to other formulas,
when group-based regression parameters were applied to individuals, no formula had a clear advantage over Bazett’s formula.19
Our study was designed to detect any differences of the corrected QT intervals during sleep and being awake in healthy children of both genders, and differences between the sexes, too.

* Corresponding author. Tel: þ44 20 71884562, Fax: þ44 20 71884556, Email: thomas.krasemann@gstt.nhs.uk
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

........7 Maximum 66 Standard deviation 8..... To minimize the problems of distinguishing between T.... which were then averaged................... Analysis of the Holter ECGs was performed with the software Mars PC version 6... We defined night as the time when all children were asleep and day as the time when all children were awake.....00–5.. and were not on any medication... If the child did not tolerate the electrodes for the whole of 24 h.......... average and standard deviation of heart rate.....74 23...........0 8..... weight and length were measured..............99 29...09 Mean 25..4 Standard deviation 1...........00 o’clock) and nighttime (0. and the sex ratio..95 Minimum 18... All channels were compared with each other.. 2 1 – ........... the number of children in each group.......3 Mean 18.. .. heart rate and QT intervals were Table 1 Number of participants Group Age (years) Number C Number F Number overall Group Age (years) Parameter Weight F (kg) Weight C (kg) ... Parents reported the time when the children were asleep and when they woke up... and QT interval. The sampling rate was 128 Hz... If a heart murmur was present.. Adult studies suggested that excessive body weight may have an influence on the QT duration........ the sum of both does not equal 24 h..5 3 5 8 8 13 6 19 14 32 4 5– ....18 5 4 9 Statistical analysis For each age group and sexes.. The study population was divided into different age groups similar to those used by Davignon et al.... if there were too many artefacts (i...3 Standard deviation 8.......... This software allows a QT measurement......6 15....... 3 3 – .. All Holter ECGs were edited manually to rule out artefacts.3 Mean 12..........5 ....... free from any chronic diseases..81 60. The included children were healthy with an unremarkable physical examination..8 43 30 73 5 6 8– .... 6 12– .6 35........97 Minimum 21................. we aimed for 17 participants of each gender in each age group.......15 Minimum 7........... model 9657578.... Siemens... the student’s t-test for related groups was used to compare the mean values of the day and night intervals. 1 6 months– . If the routine-ECG showed rhythm disturbances or the corrected QT interval exceeded 480 mL/s or rhythm disturbances were visible..7 0.... The information leaflet contained information about the inclusion criteria....and U-waves16...........74 16...3 2...4 4..5 69......2 14 21 2..1 Maximum 61...1 Maximum 15..e..12 52....14 Holter ECG was performed using hydrogel electrodes (Blazoner Medical) and digital recorders (Seer MC...... On 24 h ECG.. After a two-sided analysis of variance showed differences...1 2 3 1– ......52 35. while day time was 9 am to 7 pm............... GE Medical Systems.... T-wave amplitude very low) either lead III or V5 were used. Children with known frequent ectopics were excluded.. Thus....2 To reach a power of 80%......00–19......8 ........2 Standard deviation 2.85 ..16 34 23 57 32 91 55 7 16– ..........2 12....9 7..... echocardiography confirmed that this was innocent... Table 1 shows the different age groups.. including the fact that we were seeking healthy children free of chronic or acute diseases.......... The corrected QT interval was calculated with the use of Bazett’s formula............6 9...57 11.... A routine 12 lead ECG was performed at a paper speed of 50 mm/s and 10 mm/mV using a Megacart Elima AB... 1 6 months– ......31 .......76 Mean Minimum Maximum Standard deviation 48... It is noteworthy that due to the definition of daytime (9...1 Mean 8.... the QT-interval was measured in lead II........23...... whose parents could then decide whether their children were allowed to participate.. Table 2 shows the weight distribution...............3 3– ....0 Maximum 24...... The QT intervals were measured in 15 s intervals..1 80 13.....8 Minimum 59 Maximum 73 Standard deviation 6... Milwaukee..1 Maximum 10........1 Standard deviation 1........203 Changes of the corrected QT interval in healthy children Method Table 2 Age and weight We recruited healthy children aged 6 months to 18 years from kindergartens and schools between October 2000 and March 2002...73 Mean 35.. WI......................20 – 22 Even if this was not proven for children at the time of the recruitment..... and between the .. rhythm... The three leads were defined as shown in Figure 1.. An information leaflet was distributed to all children.....16 .12 12– ...................0 (GE Medical Systems).................8 45 72.... Bazett’s formula then was applied........ the children were excluded from the study.........4 7........ USA)... this was taken into account (see below)....... 4 5 – . only children with a weight between the 10th and 90th percentile were included...... 5 8 – ..... QT interval and corrected QT interval were calculated for each of the Holter channels over the 24 h period and for the day and night periods.. night time was between midnight and 5 am.....8 Mean 62.00 o’clock)............19 24...........12 ..71 35 73 9...........4 Minimum 11. 7 16– 18 measured in 15 s intervals.................56 7.. In all cases..73 Minimum 15..........8 17.......... Two independent investigators measured the heart rate..............

a stress ECG is used as well. In 1956. There was a suggestion that older girls had longer QTc at night in channel 3.25 – 28 Typically. Our data show that there is a significant difference between the QTc obtained from routine ECG and any of the channels of the 24 h ECG. the confidence interval in the groups with small numbers of children is relatively large. Since then. One boy was excluded for known frequent ectopics.23 An association of QT prolongation with sudden infant death syndrome has been suspected. two were excluded because their bodyweight exceeded the 90th percentile. because it is known that the corrected QT interval prolongs under physical activity. and 4821 in channel 3 (range 4108–5392). Fewer 15 s intervals were satisfactory for QTc-calculation with an average of 4692 in channel 1 (range 4342 –5528).15 One advantage of Bazett’s formula is its simplicity. Results Of 290 children screened for inclusion. These might lead to fatal Torsade de pointes and ventricular fibrillation. thus his night recording was not complete. Discussion Figure 1 Lead position for 24 h ECG. Statistical analysis was performed with software SPSS version 11. Bazett showed that the QT interval is dependent on the heart rate. The baseline ECG data are shown in Table 3. Krasemann et al. the defined night and day times are highlighted. the average corrected QT interval over 24 h is significantly longer than in the routine ECG. One boy in group 1 did not tolerate the leads for 24 h. Jervell and Lange-Nielsen24 described the long QT syndrome. Thus. which remains the most commonly used.30 Davignon et al. Microsoft Corporation USA). The QTc on the routine ECG was compared to the mean of the QTc over 24 h in each channel and for the day and night periods using student’s t-test as well.001). A 24 h ECG might be useful in these age groups if normal values for the QTc are available.19. According to our data. The Ethical Committee of the Westphalian Wilhelms University and the Aerztekammer Westfalen-Lippe approved the study on 17 May 2000. he described his formula. This is independent of the time of day. The comparison of day and night as well as both sexes concerning the parameters heart rate and QT in all channels are depicted in Table 5. sexes the student’s t-test for non-related groups was used.0. 282 children were included in the study. The night time heart rate was lower in all age groups.31 In a recent paper. Table 4 shows the average and standard deviation of the heart rate and QTc intervals in different channels. Normal values for QT intervals and corrected QT intervals in routine ECGs2 are not directly applicable to the 24 h ECG. showing more the intraindividual changes (online Supplementary figures 2–15).29 Several other formulas have been developed. Five children were on medication and were excluded as well. Chicago. measurements of the QT interval were . The quality and number of artefacts in 15 s-intervals were evenly distributed over the 24 h period. None was excluded for an abnormal corrected QT-interval. To establish or rule out the diagnosis of a long QT syndrome in adults. 2 used Bazett’s formula for the QTc calculation to establish normal values for the paediatric ECG. There was no significant difference between the sexes for the QTc in any period (Table 5).56. For a better overview. 0. 32 recently found longer maximum QTc intervals on Holter ECGs than in routine ECGs in children with Turner syndrome.5 for windows (SPSS Incorporated. usually Bazett’s formula is used. To compare the QT interval of different patients. The QTc calculated from routine ECG was approximately 40 –50 ms shorter than QTc measurements in each channel over 24 h (P . Ninety-five per cent confidence intervals were calculated and are depicted in the online Supplementary figures 2–15. 3830 in channel 2 (range 2883 – 4891). but is yet to be proven conclusively. Dalla Pozza et al. comparing routine ECG and short periods of the 24 h tape will mislead. Over the 24 h period. These differences were similar when comparing the baseline ECG QTc to any of the channels in the day and night periods alone. an average of 5422 15 s intervals (theoretical maximum of 5760) was obtained for heart rate with a range from 4624 to 5601 for the different age groups.23 This method is not applicable to small children. Unfortunately.05 was considered to be significant. It is noteworthy that in our study. For this. but not in the paediatric population. Differences between standard ECGs and ambulatory ECGs have been described previously.204 T. A P-value of . a routine ECG is obtained and the QTc calculated. several types of long QT syndrome have been described. Thus.14 As early as 1920. USA) and Microsoft Excel 2003 (11.

...........8.. our data do not allow us to answer if a shorter QTc during the 24 h study means an abnormal foreshortened QT in routine ECGs or what the cut-off for a pathologically prolonged QT-interval is..11 340 300 420 20 390 360 440 20 84 58 128 14.........................................36 – 38 we did not find significant difference of the heart rate between both sexes in all age groups................... Children aged below 6 years (in our study 54%) and all children above 11 years (in our study 64 children..........13.. heart rate slowed with increasing age..............................................................................................22 Earlier studies on corrected QT intervals in all the ECGs either had very few participants or showed methodological weaknesses........................... children are physically more active than during night time...............33... 23%) were not included.......10................................67 340 300 400 30 400 350 430 20 Mean Minimum Maximum Standard deviation 76 60 97 15...... such as heart rate.7..............45 260 200 320 60 400 360 440 40 Mean Minimum Maximum Standard deviation 112 98 144 16..... There is only one published study to date focusing on the corrected QT intervals in 24 h ECGs in healthy children...............10...........8 320 280 360 20 390 350 420 20 Mean Minimum Maximum Standard deviation 80 55 110 12...11 Different from other investigations...4 330 300 380 20 390 350 440 20 Mean Minimum Maximum Standard deviation 81 59 110 11...........35 290 260 310 20 400 390 420 10 Mean Minimum Maximum Standard deviation 96 80 118 10... these were the female infants aged 6 to 12 months and the male adolescents aged 16 to 18 years.........72 340 320 370 20 390 340 410 30 85 74 96 9........................ As expected. 5 ................... As only children with a normal QTc duration on the routine ECG were included in our study...................................... The ......... Probably............................................ In our study.........205 Changes of the corrected QT interval in healthy children Table 3 Routine ECG Group Parameter HR F (bpm) QT F (ms) QTc F (ms) HF C (bpm) QT C (ms) QTc C (ms) 1 Mean Minimum Maximum Standard deviation 125 110 138 13 270 260 290 10 390 370 420 20 146 116 192 40.. 7 not carried out exactly at the same time in routine and ambulatory ECG......... It has to be taken into account that the lead positions in the ambulatory ECG are different from the routine-ECG....... we focused on the QTc differences between day and night........ QT intervals during day time and night time were compared as well.......7............................ representing the time of day when all children were either awake or asleep.......................................................92 300 280 320 20 380 370 400 10 Mean Minimum Maximum Standard deviation 87 61 125 14..................... There were only two age groups in which we did not find a significant difference between day and night heart rate....................... and ideally a routine ECG is obtained at rest... and age...................... We think that it is essential for the comparison of QT values measured in Holter ECG to have defined leads................................................................................................................11..... the low number of participants did not allow the difference to become significant................................................15 320 280 350 20 390 350 440 20 90 65 120 11...............34 The QT interval is dependent on several physiological variables.......... 4 .... In adult studies..........35 About 25 years ago....10 Southall et al.......................... 2 ..........................................................................5............. We can assume that during day time.... as the leads are defined in the routine ECG...... 6 ..................57 310 260 320 20 390 340 420 20 102 79 125 14............................ Further studies on affected individuals with a short QT or long QT syndrome are needed to answer these questions...... we could rule out that non-identical lead positions have an influence on the QT measurement.......................... 11 and Lindinger and Hoffmann... .............7 These showed a nocturnal heart rate that was lower than the diurnal heart rate........43 290 250 320 30 390 350 420 20 114 104 133 9..................................6................... three studies on the circadian pattern of the heart rate in healthy children were carried out by Scott et al...................... This was comparable to our study............................35 This study included only 20 boys and 12 girls aged 6 to 11 years........................59 350 300 400 30 400 350 450 20 85 62 118 14............... sex.... 3 .........................88 350 330 370 20 410 390 420 10 ....... This is in concordance with earlier studies... With our defined lead position...

............ mean/STD) QTc3 (ms....................1 1– ..... mean/STD) QTc1 (ms......12 12– ... Our age groups were based on the study of Davignon et al. To have a statistical power of 80% each group should have contained a minimum of 17 children.... Especially........ and it is not clear whether the different leads were positioned in a defined manner.....8 8– ...3 3– ....16 16– 18 6 months– .12 12– ... the first year of life might be of interest because the relationship of prolonged QT interval and sudden infant death syndrome has been assumed...................5 5– ...................3 3– ........... Thus.3 3– ..... we can assume the same normal values as for adults........ mean/STD) QTc2 (ms.............3 3– ................... standard deviation......... The small number of participants in these groups might be the reason why we did not observe shorter QT intervals in the post puberty male group as described by Rautaharju et al.......2 While most of our age groups contained a reasonable number of children.8 8– ..16 16– 18 117 + 18 93 + 16 96 + 13 87 + 11 83 + 9 82 + 7 77 + 7 108 + 30 109 + 9 105 + 10 92 + 8 85 + 8 84 + 8 80 + 2 439 + 14 443 + 19 430 + 17 438 + 15 441 + 16 441 + 12 424 + 21 448 + 14 441 + 11 433 + 13 440 + 15 440 + 15 444 + 17 448 + 19 438 + 12 444 + 18 431 + 19 439 + 21 442 + 17 440 + 15 422 + 17 449 + 20 440 + 18 437 + 16 438 + 19 444 + 16 442 + 18 454 + 29 441 + 11 437 + 15 424 + 19 436 + 16 441 + 16 441 + 13 421 + 20 443 + 20 438 + 10 427 + 13 435 + 15 439 + 15 444 + 17 447 + 18 6 months– ..39 while we used digital data storage to avoid undulations............ 24 h F C ....................1 1– ... Krasemann et al.......8 8– ...........5 5– ...................... study has another disadvantage compared to our study: the Holter recorder only had two channels......................... Historical studies have used tape recorders...........12 12– ....1 1– .. a few did not: for the 16 to 18 year old children.................... as typically these adolescents already finished their puberty.......... night...... day.......35............ there is no other study on the subject in these age groups available...8 8– .12 12– ....5 5– . Unfortunately..3 3– ... we were not forced to increase the numbers of subjects.............. ...5 5– ........16 16– 18 128 + 16 106 + 21 110 + 14 98 + 14 93 + 11 93 + 8 86 + 12 115 + 33 123 + 9 119 + 9 105 + 10 95 + 11 95 + 10 89+5 439 + 13 445 + 20 434 + 17 438 + 15 440 + 16 441 + 12 425 + 20 442 + 18 443 + 12 436 + 13 440 + 14 438 + 13 443+15 446+19 440 + 15 445 + 18 433 + 22 440 + 21 442 + 18 440 + 16 425 + 15 447 + 18 442 + 20 439 + 18 439 + 20 445 + 14 443+19 453+30 442 + 9 441 + 18 426 + 19 434 + 15 438 + 16 441 + 12 422 + 18 438 + 25 439 + 11 426 + 15 433 + 15 435 + 14 440+17 443+18 6 months– ..1 1– ......12 12– ......206 T......12 12– . Day F C ..3 3– ....................8 8– .......16 16– 18 97+20 80+15 79+11 72+9 68+9 64+7 62+9 102+24 93+9 89+9 76+8 71+8 70+8 63+1 441+20 444+22 423+24 439+17 444+20 442+17 421+21 453+9 440+10 431+14 432+51 441+22 448+24 451+19 440+16 445+17 427+24 439+23 445+25 4391+21 415+25 453+25 442+19 437+18 432+52 443+25 441+21 455 + 29 442+18 438+18 422+22 440+19 446+20 443+18 420+24 451+15 4404+13 427+12 431+51 443+20 447+20 451 + 18 ................... Night F C STD..40 It is less satisfactory to have only a small number of children in the infant age groups (6 months to 3 years)..1 1– ................5 5– .. Table 4 24 h ECG Daytime Gender Age (years) Heart rate (bpm...8 8– ............27 The values obtained from the other groups can be used as guide values to interpret QTc measurements in Holter ECGs obtained from children (Table 4)................5 5– .................................... mean/STD) 6 months– ............1 1– ..........16 16– 18 6 months– .16 16– 18 6 months– .........

....2688 16– 18 ........6731 0......0078 5 – ...7060 0..0886 0.38 Our study did not show any significant differences between both sexes in any age group.6677 16– 18 0.5452 0...1712 0...1765 0..5385 0......8496 0.3 QTc2 .1074 0.12 0.. F (night) P5 ..4285 0.0228 0.. but interestingly these were not significant in all groups.. We hope to add some sufficient data for the interpretation of the paediatric 24 h and routine ECG.7137 0.5990 0.4472 0........ While the heart rate showed typical differences between night and day......0018 0...7085 0.......9648 0...7233 0......5 0...3169 0........207 Changes of the corrected QT interval in healthy children Table 5 Differences of heart rate and QTc between day and night.4842 0.3012 0.1 1 – . but it is much more likely to miss them in a routine ECG..........5353 0..0001 0.5868 0...36.3314 16– 18 0.7838 0.....5579 0....16 0.....4744 16– 18 0. because...... One has to take into account that mathematically significant differences here show an absolute maximum of 10 ms..........3 3 – ......2099 0..6403 0...0001 0.8885 0..0705 0......2442 0.12.....5179 0. The routine ECG seems to be a good screening method for the measurement of corrected QT intervals.0008 0......0969 0.16 0..........6558 0....6864 0.0919 0.......3376 0.........................2725 0.......6666 0...4026 0.6172 0.....12 12– ............5 0...............5124 0......4491 8 – ....5094 0..4738 0.8075 0.3905 12– ..9261 0..0603 0.. It is not clear whether this is a statistical problem (small number of participants) or is caused by methodological weakness (lead position not defined)..4604 0.0417 <0....7473 3 – .....7873 0...0001 <0..8 8 – ..2692 0.0217 0......1233 0............ the QTc interval differs between genders in the routine ECG..........8577 0...............0065 <0...4144 0.....8472 0...8504 .......6529 0.4071 5 – ....8 <0. 6 months– .....6934 0..... we only accepted children with a body weight between the 10th and 90th percentile....6300 0.....8081 0.0001 <0......1 1 – ....1486 0...0266 0........ or not in all leads (Table 5)........0273 0.........1012 0.5 0..7430 0..........1251 0....0009 0.. In adults...... F (24 h) P5 C vs...1787 5 – .0001 <0............4915 0...............1 HF 1 – ...........0030 0.......33....8322 0..........1709 0...0001 0.......12 12– .........3297 0...................1160 0......’ ...... One could assume that rapid QT changes might be overseen in a 24 h ECG....6939 0. Molnar et al.......16 <0.3785 0....... because the corrected QT interval is kept constant over the whole day..........8912 0..6881 0....0001 <0............. The QTc was shorter while the adults were awake.0566 0. With increased number of participants in the different age groups.......3816 0....7446 0. night (F) P5 Day vs..0604 0....3841 0.. F (day) P5 C vs..... we could not find this for the QTc interval...8969 0.......1 QTc1 1 – ......5707 0..0837 There were only a few significant differences of the QTc interval between night and day time..0587 0..........1105 0.9846 0.........0287 0...2455 0......41 To rule out the influence of abnormal body weight.........0001 <0....3265 0...5 5 – .3 3 – . Our definition of day and night was based on parental observations and therefore we could be certain when all children were either asleep or awake during the defined times.................. 6 months– .8486 0...... night (C) P5 C vs..7961 0...0001 0....8456 0........16 0......0182 0.8 0....5681 0....8848 0..1135 0.0004 0....3 QTc3 3 – .......0001 <0.. 6 months– ..7026 12– .. and between the genders (significancant values are boldfaced) Age (years) Parameter Day vs.8826 0.1839 0..5340 0..5240 0.7708 0.... More recent studies have shown that the obesity leads to prolonged QT intervals and QTc prolongation as well.......0444 8 – .....8029 0.....0090 0.......... the confidence interval becomes smaller..7667 0.12 0.......0142 0..8393 0..8 8 – ....9327 0.1585 0.......... 6 months– ...... 33 showed a marked change in the QTc interval over 24 h in 21 adults.8157 0. as Frank Wilson pointed out:3 ‘There are comparatively few people who are not in greater danger of having their peace and happiness destroyed by an erroneous diagnosis of cardiac abnormality based on a faulty interpretation of an electrocardiogram than being injured or killed by an atomic bomb......6624 0.7205 0...5162 0.2635 0.............. The clinical bearing of these differences is not yet clear.

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