The Development of Circadian Rhythms in Human Infants

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proportion of the total variance of the observed data that is „explained‟ by the fitting pattern. For the 93 infant weeks that were sampled the mean amplitude was 0.0288 with maximum and minimum values 0.0035 and 0.1092 respectively. The resultant graphs for infants 16003 and 16004 are shown for direct comparison (Fig 8.3.). Data on all infants is included in appendix 4. Graphs were drawn using R statistical package (R version 2.7.2 2008 The R Foundation for Statistical Computing). For clarity a description of the symbols used in the gene plots and a key are given below: Separate graphs have been prepared for each observed week of each infant showing the level of expression plotted against time, with two curves superimposed: i) the fitted sinusoidal curve for that week‟s data, as an unbroken line and ii) the fitted sinusoidal curve from the week (for the same infant) that has the best fit, corresponding to the greatest amplitude of the pattern, as a broken line. In other words, the week with greatest amplitude of gene expression was superimposed (represented by broken line) onto each week of individual measurement (represented by unbroken line) for ease of comparison. For each infant, therefore, the plot for that week with the best fit does not have a second curve superimposed. Each of these graphs is annotated with the amplitude, hour of maximum fitted level, the R-squared statistic, and the P-value from that individual linear regression 176
Raw data points are represented by open circles. The best fit curves for the raw data are represented by an unbroken continuous line. The curve for the week with the best sinusoidal curve for all weeks of measurement is represented using a broken line on these weeks. The week of best fit for gene expression is shown the week the open circles and sine wave curve have the closest fit. On this week there is a solitary is continuous unbroken line representing line of best fit. Sine wave curves had the following standardised values calculated. distance between maximum and minimum point of sine wave Amp � 2 2 � � Rsq � measure of goodness of best fit R Peak hour gives the clock time that maximum amplitude for gene expression was achieved. The week of best fit had the highest values for amplitude (Amp) and R 2 . For infant 16003 the week of best fit for clock gene expression is week 11 (week of highest amplitude and with corresponding R 2 values). For infant 16004 this occurs at week 18. H3f3b appears to cycle at some weeks of measurements for most infants (see appendix 4). The cycle was not present in all weeks. On visual inspection for a percentage of the infants, the initial weeks had no cycle and the depth of amplitude 177
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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
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There is general agreement, that al
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Summary 1. Development encompasses
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Figure 1.1 - Diagram illustrating c
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A phase shift is used to describe a
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1.4 Ontogeny in Human Infants Well
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1.5.2 Circadian Rhythms in Temperat
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1.5.4 Factors affecting Temperature
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1.6 Melatonin (Reviewed in Cardinal
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mechanism by which this occurs is n
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It is at this time that infant slee
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1.7 Cortisol Cortisol is a hormone,
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1.7.3 Circadian pattern of Cortisol
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In a separate study, Weerth et al u
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Summary 1. Cortisol is crucial to a
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NREM sleep has 4 stages. It occupie
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1.8.1 Functions of Sleep The functi
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1.8.3 Ontogeny of Sleep in Infants
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Sleep can clearly be used as marker
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For the purpose of this study, the
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Summary 1. Sleep is defined by lack
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Overall the SCN generates signals (
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Figure 1.2 - The mammalian circadia
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1.9.3 Molecular Components of the C
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Figure 1.3 - Mechanisms from SCN to
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1.9.7 Melatonin and Clock Melatonin
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The links between the central clock
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Chapter 2 Methods
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There were strict inclusion and exc
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This personal contact on the postna
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2.1.3 Home monitoring visits The fi
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2.1.4 Further monitoring informatio
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Core body temperature was taken sim
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2.3 Collection of urine samples Pai
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were read against air at 429 nm aft
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allowed the display and comprehensi
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2.8.1 RNA preparation and cDNA synt
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In total three methods were trialle
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2.11 Statistical methods For compar
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test that each infant‟s height an
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Power calculation Sample size: Fift
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3 Results 3.1 Recruited subjects an
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predominantly affluent areas of the
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Birth history and past medical hist
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3.1.3 Socioeconomic demographics of
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her best friend losing her battle w
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Sleep environment of infants All mo
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Summary 1. This study had higher ra
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4 Results 4.1 Core body temperature
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Degrees Celsius 36.70 36.60 36.50 3
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11-13 weeks There is no significant
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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
Page 135 and 136: Figure 5.4 - Changes in night time
Page 137 and 138: Night-day difference in melatonin s
Page 139 and 140: Summary 1. There is an increase in
Page 141 and 142: 6 Results DESCRIPTION OF THE URINAR
Page 145 and 146: 6.1.2 Emergence of diurnal rhythm f
Page 147 and 148: Figure 6.3 - Histogram showing dist
Page 151 and 152: Cortisol values were corrected to a
Page 153 and 154: 6.1.4 Relationship between night an
Page 155 and 156: Chapter 7 Results
Page 157 and 158: Mean Length of Sleep/ Wake Bouts Th
Page 159 and 160: Sleep parameters were recorded as m
Page 161 and 162: 7.3 Development of infant sleep rel
Page 163 and 164: Figure 7.2 - Changes in infant slee
Page 165 and 166: Figure 7.4 - Changes in percentage
Page 167 and 168: Figure 7.5 - Changes in infant frag
Page 169 and 170: Figure 7.7 - Changes in number of m
Page 171 and 172: Figure 7.9 - Changes in the percent
Page 173 and 174: Sleep efficiency (%) 100.0 90.0 80.
Page 175 and 176: Chapter 8 Results
Page 177 and 178: Considering only those weeks of mea
Page 179 and 180: 8.2 Description of peripheral gene
Page 181 and 182: 18:30 hours 0.9927; 01:00 ours 1.01
Page 183 and 184: The weeks after temperature maturat
Page 185: Further peripheral gene graphical r
Page 189 and 190: H3f3b/Gap H3f3b/Gap H3f3b/Gap H3f3b
Page 191 and 192: 8.3 Detailed gene expression analys
Page 193 and 194: Summary 1. H3f3b was selected as ge
Page 195 and 196: 9 Results FACTORS AFFECTING SLEEP A
Page 197 and 198: Care and infant related factors �
Page 199 and 200: Table 9.3 - Effect of family occupa
Page 201 and 202: * Class 7 used as reference group
Page 203 and 204: Table 9.6 - Effect of measured infa
Page 205 and 206: Summary: 1. A mature physiological
Page 207 and 208: 10 Results 10.1 Circadian rhythms -
Page 209 and 210: value of above 0.5 for R squared wa
Page 211 and 212: Table 10.1 - Temporal relationship
Page 213 and 214: Chapter 11 Discussion
Page 215 and 216: � What if any are the factors whi
Page 217 and 218: 11.1 Physiological development - ag
Page 219 and 220: There are other proven factors whic
Page 221 and 222: drawbacks of the spread of data - a
Page 223 and 224: presented in table 6.1 do not have
Page 225 and 226: separate methods were applied to th
Page 227 and 228: significant. Sleep latency was cons
Page 229 and 230: The function of sleep in developmen
Page 231 and 232: Melatonin secretion was higher on n
Page 233 and 234: In this study sleeping in the same
Page 235 and 236: 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
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Mirmiran, M. & Ariagno, R.L., 2000.
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Rawson, D., Petersen, S.A., Wailoo,
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Stokkan, K.A., Yamazaki, S., Tei, H
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Winter, J.S.D., 1985. The adrenal c
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