The Development of Circadian Rhythms in Human Infants

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The following questions are to be addressed in this thesis. � What is the pattern of physiological development in human infants in overnight core body temperature during sleep during the first four postnatal months and what is the nature of the change (gradual versus abrupt)? � Is there a pattern of change of cortisol secretion in human infants in the early postnatal period and how does it relate to maturation of body temperature? � Is there a pattern in the secretion of melatonin with increase in postnatal age and how does it relate to physiological maturation state in terms of core body temperature? � What are the characteristics changes in infant night time sleep as babies get older and is there any relationship with physiological development using overnight core body temperature as a marker of maturity? � What if any are the factors which have an effect on the development of core body temperature maturation, secretion of cortisol and melatonin and the development of infant sleep? � Is there any suggestion of ordering/timing of physiological events in human infants in the first four postnatal months? � Can the genetic output of the clock be detected and measured in human infants from buccal swabs and are there any longitudinal changes with age? 56
Chapter 2 Methods
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The Development of Circadian Rhythm
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Table of Contents LIST OF FIGURES .
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7.1 Analysis of infant sleep measur
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List of Figures Figure 1.1 - Diagra
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List of Tables Table 3.1 - Descript
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1 Introduction Happiness is not a m
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Each of these independently is impo
Page 15 and 16: There is general agreement, that al
Page 17 and 18: Summary 1. Development encompasses
Page 19 and 20: Figure 1.1 - Diagram illustrating c
Page 21 and 22: A phase shift is used to describe a
Page 23 and 24: 1.4 Ontogeny in Human Infants Well
Page 25 and 26: 1.5.2 Circadian Rhythms in Temperat
Page 27 and 28: 1.5.4 Factors affecting Temperature
Page 29 and 30: 1.6 Melatonin (Reviewed in Cardinal
Page 31 and 32: mechanism by which this occurs is n
Page 33 and 34: It is at this time that infant slee
Page 35 and 36: 1.7 Cortisol Cortisol is a hormone,
Page 37 and 38: 1.7.3 Circadian pattern of Cortisol
Page 39 and 40: In a separate study, Weerth et al u
Page 41 and 42: Summary 1. Cortisol is crucial to a
Page 43 and 44: NREM sleep has 4 stages. It occupie
Page 45 and 46: 1.8.1 Functions of Sleep The functi
Page 47 and 48: 1.8.3 Ontogeny of Sleep in Infants
Page 49 and 50: Sleep can clearly be used as marker
Page 51 and 52: For the purpose of this study, the
Page 53 and 54: Summary 1. Sleep is defined by lack
Page 55 and 56: Overall the SCN generates signals (
Page 57 and 58: Figure 1.2 - The mammalian circadia
Page 59 and 60: 1.9.3 Molecular Components of the C
Page 61 and 62: Figure 1.3 - Mechanisms from SCN to
Page 63 and 64: 1.9.7 Melatonin and Clock Melatonin
Page 65: The links between the central clock
Page 69 and 70: There were strict inclusion and exc
Page 71 and 72: This personal contact on the postna
Page 73 and 74: 2.1.3 Home monitoring visits The fi
Page 75 and 76: 2.1.4 Further monitoring informatio
Page 77 and 78: Core body temperature was taken sim
Page 79 and 80: 2.3 Collection of urine samples Pai
Page 81 and 82: were read against air at 429 nm aft
Page 83 and 84: allowed the display and comprehensi
Page 85 and 86: 2.8.1 RNA preparation and cDNA synt
Page 87 and 88: In total three methods were trialle
Page 89 and 90: 2.11 Statistical methods For compar
Page 91 and 92: test that each infant‟s height an
Page 93 and 94: Power calculation Sample size: Fift
Page 95 and 96: 3 Results 3.1 Recruited subjects an
Page 97 and 98: predominantly affluent areas of the
Page 99 and 100: Birth history and past medical hist
Page 101 and 102: 3.1.3 Socioeconomic demographics of
Page 103 and 104: her best friend losing her battle w
Page 105 and 106: Sleep environment of infants All mo
Page 107 and 108: Summary 1. This study had higher ra
Page 109 and 110: 4 Results 4.1 Core body temperature
Page 111 and 112: Degrees Celsius 36.70 36.60 36.50 3
Page 113 and 114: 11-13 weeks There is no significant
Page 115 and 116: Core body temperature (degrees Cels
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Number of infants 10 8 6 4 2 0 7 8
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Mean minimum rectal temperature in
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Mean minimum rectal temperature in
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Figure 4.7 shows the changes in the
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Chapter 5 Result
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4 or 6 hourly samples. Circadian rh
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Figure 5.1 - Distribution of mean n
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5.1.2 Emergence of diurnal rhythm f
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Figure 5.3 - Histogram showing dist
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Figure 5.4 - Changes in night time
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Night-day difference in melatonin s
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Summary 1. There is an increase in
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6 Results DESCRIPTION OF THE URINAR
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6.1.2 Emergence of diurnal rhythm f
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Figure 6.3 - Histogram showing dist
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Cortisol values were corrected to a
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6.1.4 Relationship between night an
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Chapter 7 Results
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Mean Length of Sleep/ Wake Bouts Th
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Sleep parameters were recorded as m
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7.3 Development of infant sleep rel
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Figure 7.2 - Changes in infant slee
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Figure 7.4 - Changes in percentage
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Figure 7.5 - Changes in infant frag
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Figure 7.7 - Changes in number of m
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Figure 7.9 - Changes in the percent
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Sleep efficiency (%) 100.0 90.0 80.
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Chapter 8 Results
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Considering only those weeks of mea
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8.2 Description of peripheral gene
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18:30 hours 0.9927; 01:00 ours 1.01
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The weeks after temperature maturat
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Further peripheral gene graphical r
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Raw data points are represented by
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H3f3b/Gap H3f3b/Gap H3f3b/Gap H3f3b
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8.3 Detailed gene expression analys
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Summary 1. H3f3b was selected as ge
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9 Results FACTORS AFFECTING SLEEP A
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Care and infant related factors �
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Table 9.3 - Effect of family occupa
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* Class 7 used as reference group
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Table 9.6 - Effect of measured infa
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Summary: 1. A mature physiological
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10 Results 10.1 Circadian rhythms -
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value of above 0.5 for R squared wa
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Table 10.1 - Temporal relationship
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Chapter 11 Discussion
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� What if any are the factors whi
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11.1 Physiological development - ag
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There are other proven factors whic
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drawbacks of the spread of data - a
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presented in table 6.1 do not have
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separate methods were applied to th
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significant. Sleep latency was cons
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The function of sleep in developmen
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Melatonin secretion was higher on n
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In this study sleeping in the same
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Timing of sleep maturation was diff
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systematic, ordered developmental p
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individual gene plots that provide
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temperature recording devices adapt
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Both melatonin and cortisol rhythms
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Extension of this period of monitor
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Second, we demonstrated the gene of
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Cortisol and melatonin Slope based
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Summary and Future work This study
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� Maximise technique for measurin
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“There is a science of infant car
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References
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Bajanowski, T., Vege, Å., Byard, R
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Chamley, C.A., Carson P, Randall D,
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Frank, M.G., Heller, H.C., 2003. Th
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intrahypothalamic administration of
Page 267 and 268:
Mirmiran, M. & Ariagno, R.L., 2000.
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Rawson, D., Petersen, S.A., Wailoo,
Page 271 and 272:
Stokkan, K.A., Yamazaki, S., Tei, H
Page 273 and 274:
Winter, J.S.D., 1985. The adrenal c
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The Development of Circadian Rhythms in Human Infants

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