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We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
Three-dimensional (3D) wafer-level integration is receiving increased attention with various wafer bonding approaches being evaluated. Recently, we explored an alternative lowtemperature Ti/Si-based wafer bonding, in which an oxidized silicon wafer was successfully bonded with a prime silicon wafer at 400°C using 30 nm sputtered Ti as adhesive. The bonded pairs show excellent bonding uniformity and mechanical integrity. Rutherford backscattering spectrometry (RBS) was applied to confirm the interdiffusion occurred in the interlayer. The bonding interface was examined by high-resolution transmission electron microscopy (HRTEM) assisted with electron energy loss spectroscopy (EELS) elemental mapping and energy dispersive X-ray spectroscopy (EDX). Characterization of the bonding interface indicates the strong adhesion achieved is attributed to an amorphous layer formed by interdiffusion of Si and oxygen into Ti interlayer and the unique ability to reduce native oxide (SiO2) by Ti even at low temperatures.
After the initial resuscitation of an encephalopathic infant, the extended management of the patient becomes critical in order to prevent as much secondary damage as possible. There are many different management protocols that are acceptable, and it is not the intent of this chapter to review all of them used for the various conditions encountered in neonatal intensive care. Rather, we focus on the early transitional period following birth and resuscitation, during which the condition of the depressed infant can be substantially improved by expert care.
As noted in Chapters 2 and 42, the encephalopathic period involves a continuum of biologic events associated with secondary energy failure lasting up to 48–72 hours after the initial insult. These include the reperfusion period with the elaboration of oxygen free radicals and various cytokines as well as necrosis and apoptosis that then ensue. It is imperative that the extended management of these infants be carried out in an optimal fashion at a center that can provide hypothermia or other novel neuroprotective interventions that may be developed.
Unfortunately, the windows of opportunity may be short and variable depending upon the nature of the intervention, and could change as further research informs practice. Thus there is an obligation for the practitioner to be well informed about progress in the standard of care and to stay current with respect to neuroprotective strategies. Various neuroprotective mechanisms after hypoxic–ischemic injury are discussed in detail in Chapter 42.
The term kernicterus was originally used to describe the deposition of bilirubin in the basal ganglia. It was first described in 1903 by Schmorl. More recently, the term has also been used in reference to the chronic and permanent clinical sequelae of bilirubin toxicity. For the acute manifestations of bilirubin toxicity, the term acute bilirubin encephalopathy or ABE has been adopted. Another acronym, BIND, has been adopted to describe any bilirubin-induced neurologic dysfunction. Although technically the diagnosis of kernicterus can only be confirmed at autopsy, brain magnetic resonance imaging (MRI) studies may now aid in the confirmation of the diagnosis in a living child with severe jaundice. The MRI signature for kernicterus includes high signal intensity on T1-weighted (T1W) images in the globus pallidus, internal capsule, thalamus, and hippocampi (Fig. 27.1). The associated T2W images have abnormal increased signal in the globus pallidus and thalamus in the same regions as the high signal on the T1W images (Fig. 27.2). Loss of demarcation between globus pallidus, internal capsule, and the anterior thalamus was the major finding. The source of these abnormal signals has not been definitively identified, and therefore the MRI findings should not be considered diagnostic in themselves, but only consistent with the diagnosis of kernicterus in the context of severe neonatal jaundice and the acute and chronic clinical features of bilirubin toxicity (Table 27.1).
Following the birth of a depressed newborn, the infant's caretakers are involved in providing appropriate resuscitative techniques, stabilizing the infant's biochemical and physiological abnormalities, and evaluating the infant's response to these measures. The caretakers must also ascertain the cause of the infant's depression, attempt to determine when the event or events leading to the depression occurred, and develop a plan for follow-up evaluation and treatment that will be required. The determination of causation and timing not only has medical–legal implications, but also is becoming extremely important in order to evaluate the types of therapy that may be utilized to mitigate the effects of an asphyxial event. If the infant had suffered significant damage days or weeks prior to birth, then these rescue forms of therapy will have little, if any, beneficial effect on the infant's eventual outcome. In many situations, this determination is very difficult to make, as there may be a myriad of events that could have occurred prior to the time of birth, and overlapping of significant problems makes this exercise an almost impossible task at times.
Identification of the etiology of a cerebral injury is a critical prerequisite to the determination of its timing. For example, lactic acidemia immediately after birth and an elevated serum creatine kinase (CK) level at 24 hours of age in an infant with abnormal intensities of T1- and T2-weighted signals in the basal ganglia on MRI obtained at 2 weeks of age might point to intrapartum timing of an acute hypoxic–ischemic insult.
To evaluate the 137-item Utah Picture-sort Food-frequency Questionnaire (FFQ) in the measurement of usual dietary intake in older adults.
The picture-sort FFQ was administered at baseline and again one year later. Three seasonal 24-hour dietary recall interviews were collected during the year between the two FFQs. Mean nutrient intakes were compared between methods and between administrations of the FFQ.
The FFQ interviews were administered in respondents' homes or care-centres. The 24-hour diet recalls were conducted by telephone interview on random days of the week.
Two-hundred-and-eight men and women aged 55–84 years were recruited by random sample of controls from a case–control study of nutrition and bone health in Utah.
After adjustment for total energy intake, median Spearman rank correlation coefficients between the two picture-sort FFQs were 0.69 for men aged ≤69 years, 0.66 for men aged >69 years; and 0.68 for women aged ≤69 years, 0.67 for women aged >69 years. Median correlation coefficients between methods were 0.50 for men ≤69 years old, 0.52 for men >69 years old; 0.55 for women ≤69 years old, 0.46 for women >69 years old.
We report intake correlations between methods and administrations comparable to those reported in the literature for traditional paper-and-pencil FFQs and one other picture-sort method of FFQ. This dietary assessment method may improve ease and accuracy of response in this and other populations with low literacy levels, poor memory skill, impaired hearing, or poor vision.
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