X-ray tomography for the advancement of laser powder bed fusion additive manufacturing.

X-ray computed tomography is a powerful tool to nondestructively inspect additively manufactured parts. Additive manufacturing of metals, especially laser powder bed fusion, is increasingly being adopted for serial production of critical components in aerospace, automotive and various other industries. The technology holds huge potential for more efficient material usage and light weighting of components, among the many advantages. As this new production method is being ramped up and refined in various industry sectors, X-ray tomography is critical to the advancement of the quality of the produced components. X-ray tomography allows the nondestructive evaluation of the structural integrity of the parts produced, which in turn provides confidence in the expected performance of the parts. Besides final inspection of parts for porosity/defects and dimensional tolerances for a pass/fail decision, X-ray tomography also has a critical role to play in advancing and improving the additive manufacturing processes. This process improvement refers to the inspection of small representative coupon samples on a microscopic scale, in order to optimize the process parameters such as laser power, speed, scan strategy and various others. In this work, we describe the evaluation of small solid cube coupon samples and lattice structure coupon samples. These examples are meant to improve the understanding of the potential of X-ray tomography in advancing additive manufacturing processes (in contrast to its usual use for nondestructive testing of final parts), thereby providing support towards qualification of these processes and the parts produced in these processes. X-ray tomography, therefore, plays a key role in the adoption and qualification of high-quality metal additive manufacturing.

Delayed cortical development in fetuses with complex congenital heart disease.

Neurologic impairment is a major complication of complex congenital heart disease (CHD). A growing body of evidence suggests that neurologic dysfunction may be present in a significant proportion of this high-risk population in the early newborn period prior to surgical interventions. We recently provided the first evidence that brain growth impairment in fetuses with complex CHD has its origins in utero. Here, we extend these observations by characterizing global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a progressive third trimester fall-off in cortical gray and white matter volumes (P < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS. Significant delays in cortical gyrification were also evident in HLHS fetuses (P < 0.001). In the HLHS fetus, local cortical folding delays were detected as early as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions and appear to precede volumetric brain growth disturbances, which may be an early marker of elevated risk for third trimester brain growth failure.

Impact of a multidisciplinary approach to ultrasound- guided thyroid fine-needle aspiration biopsy at Tygerberg Hospital, Cape Town, South Africa: A retrospective audit.

BACKGROUND: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA). OBJECTIVES: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA. METHODS: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics. RESULTS: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient. CONCLUSIONS: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

Mechanisms of fatigue crack initiation and propagation in auxetic meta-biomaterials.

The fatigue performance of additively manufactured auxetic meta-biomaterials made from commercially pure titanium has been studied only recently. While certain assumptions have been made regarding the mechanisms underlying their fatigue failure, the exact mechanisms are not researched yet. Here, we studied the mechanisms of crack formation and propagation in cyclically loaded auxetic meta-biomaterials. Twelve different designs were subjected to compression-compression fatigue testing while performing full-field strain measurement using digital image correlation (DIC). The fatigue tests were stopped at different points before complete specimen failure to study the evolution of damage in the micro-architecture of the specimens using micro-computed tomography (micro-CT). Furthermore, finite element models were made to study the presence of stress concentrations. Structural weak spots were found in the inverted nodes and the vertical struts located along the outer rim of the specimens, matching the maximum principal strain concentrations and fracture sites in the DIC and micro-CT data. Cracks were often found to originate from internal void spaces or from sites susceptible to mode-I cracking. Many specimens maintained their structural integrity and exhibited no signs of rapid strain accumulation despite the presence of substantial crack growth. This observation underlines the importance of such microscale studies to identify accumulated damage that otherwise goes unnoticed. The potential release of powder particles from damaged lattices could elicit a foreign body response, adversely affecting the implant success. Finding the right failure criterion, therefore, requires more data than only those pertaining to macroscopic measurements and should always include damage assessment at the microscale. STATEMENT OF SIGNIFICANCE: The negative Poisson's ratio of auxetic meta-biomaterials makes them expand laterally in response to axial tension. This extraordinary property has great potential in the field of orthopedics, where it could enhance bone-implant contact. The fatigue performance of additively manufactured auxetic meta-biomaterials has only recently been studied and was found to be superior to many other bending- and stretch-dominated micro-architectures. In this study, we go beyond these macroscopic measurements and focus on the crack initiation and propagation. Full-field strain measurements and 3D imaging are used to paint a detailed picture of the mechanisms underlying fatigue. Using these data, specific aspects of the design and/or printing process can be targeted to improve the performance of auxetic meta-biomaterials in load-bearing applications.

Regional Differences in Gamma-Aminobutyric Acid and Glutamate Concentrations in the Healthy Newborn Brain.

BACKGROUND AND PURPOSE: Gamma-aminobutyric acid and glutamate system disruptions may underlie neonatal brain injury. However, in vivo investigations are challenged by the need for special 1H-MR spectroscopy sequences for the reliable measurement of the neurotransmitters in this population. We used J-edited 1H-MR spectroscopy (Mescher-Garwood point-resolved spectroscopy) to quantify regional in vivo gamma-aminobutyric acid and glutamate concentrations during the early postnatal period in healthy neonates. MATERIALS AND METHODS: We prospectively enrolled healthy neonates and acquired Mescher-Garwood point-resolved spectroscopy spectra on a 3T MR imaging scanner from voxels located in the cerebellum, the right basal ganglia, and the right frontal lobe. CSF-corrected metabolite concentrations were compared for regional variations and cross-sectional temporal trends with advancing age. RESULTS: Fifty-eight neonates with acceptable spectra acquired at postmenstrual age of 39.1 (SD, 1.3) weeks were included for analysis. Gamma-aminobutyric acid (+ macromolecule) (2.56 [SD, 0.1]) i.u., glutamate (3.80 [SD, 0.2]), Cho, and mIns concentrations were highest in the cerebellum, whereas NAA (6.72 [SD, 0.2]), NAA/Cho, Cr/Cho, and Glx/Cho were highest in the basal ganglia. Frontal gamma-aminobutyric acid (1.63 [SD, 0.1]), Glx (4.33 [SD, 0.3]), Cr (3.64 [SD, 0.2]), and Cho concentrations were the lowest among the ROIs. Glx, NAA, and Cr demonstrated a significant adjusted increase with postmenstrual age (ß = 0.2-0.35), whereas gamma-aminobutyric acid and Cho did not. CONCLUSIONS: We report normative regional variations and temporal trends of in vivo gamma-aminobutyric acid and glutamate concentrations reflecting the functional and maturational status of 3 distinct brain regions of the neonate. These measures will serve as important normative values to allow early detection of subtle neurometabolic alterations in high-risk neonates.

Mechanical behavior of in-situ alloyed Ti6Al4V(ELI)-3 at.% Cu lattice structures manufactured by laser powder bed fusion and designed for implant applications.

In the present study, cellular lattice structures for implant applications are reported for the first-time incorporating copper directly by in-situ alloying in the laser powder bed fusion process. The aim to incorporate 3 at.% Cu into Ti6Al4V(ELI) is selected for improved antibacterial properties while maintaining appropriate mechanical properties. Previously, topologically optimized Ti6Al4V(ELI) lattice structures were successfully designed, manufactured and studied for implant applications. The development of a new alloy produced by in-situ alloying of elemental powder mixture of Ti6Al4V(ELI) and pure Cu powders was used here for the production of identical lattice structures with improved antibacterial properties. One of the same as-designed CAD models was used for the manufacturing of these lattices compared to previous work on pure Ti6Al4V(ELI) lattices, making direct comparison of mechanical properties possible. Similar manufacturability highlights the applicability of this alloying technique to other lattice designs. Microstructural characterization was performed by optical and electron microscopies, as well as microCT. Mechanical characterization was performed by means of compression tests and hardness measurements. Results showed that in-situ alloying with copper leads to the formation of localized Cu-rich regions, refinement of martensitic phase and the formation of CuTi2 intermetallic precipitates, which increased the hardness and strength of the material. Deviations in wall thickness between the as-designed and as-manufactured lattices led to anisotropy of the mechanical properties of the lattices. Higher compressive strength values were obtained when thicker walls were oriented along the loading direction. Nevertheless, alloying with Cu had a higher impact on the compressive strength of lattice structure than the wall thickness deviations. The direct in-situ alloying of copper in Ti6Al4V(ELI) is a promising route for direct manufacturing of antibacterial implants.

Fatigue performance of auxetic meta-biomaterials.

Meta-biomaterials offer a promising route towards the development of life-lasting implants. The concept aims to achieve solutions that are ordinarily impossible, by offering a unique combination of mechanical, mass transport, and biological properties through the optimization of their small-scale geometrical and topological designs. In this study, we primarily focus on auxetic meta-biomaterials that have the extraordinary ability to expand in response to axial tension. This could potentially improve the longstanding problem of implant loosening, if their performance can be guaranteed in cyclically loaded conditions. The high-cycle fatigue performance of additively manufactured (AM) auxetic meta-biomaterials made from commercially pure titanium (CP-Ti) was therefore studied. Small variations in the geometry of the re-entrant hexagonal honeycomb unit cell and its relative density resulted in twelve different designs (relative density: ~5-45%, re-entrant angle = 10-25°, Poisson's ratio = -0.076 to -0.504). Micro-computed tomography, scanning electron microscopy and mechanical testing were used to respectively measure the morphological and quasi-static properties of the specimens before proceeding with compression-compression fatigue testing. These auxetic meta-biomaterials exhibited morphological and mechanical properties that are deemed appropriate for bone implant applications (elastic modulus = 66.3-5648 MPa, yield strength = 1.4-46.7 MPa, pore size = 1.3-2.7 mm). With an average maximum stress level of 0.47 σy at 106 cycles (range: 0.35 σyσy- 0.82 σyσy), the auxetic structures characterized here are superior to many other non-auxetic meta-biomaterials made from the same material. The optimization of the printing process and the potential application of post-processing treatments could improve their performance in cyclically loaded settings even further. STATEMENT OF SIGNIFICANCE: Auxetic meta-biomaterials have a negative Poisson's ratio and, therefore, expand laterally in response to axial tension. Recently, they have been found to restore bone-implant contact along the lateral side of a hip stem. As a result, the bone will be compressed along both of the implant's contact lines, thereby actively reducing the risk of implant failure. In this case the material will be subjected to cyclic loading, for which no experimental data has been reported yet. Here, we present the first ever study of the fatigue performance of additively manufactured auxetic meta-biomaterials based on the re-entrant hexagonal honeycomb. These results will advance the adoption of auxetic meta-biomaterials in load-bearing applications, such as the hip stem, to potentially improve implant longevity.

Neurodevelopmental outcome of fetuses referred for ventriculomegaly.

OBJECTIVE: To characterize the delivery and postnatal neurodevelopmental outcomes of fetuses referred for ventriculomegaly (VM). METHODS: Under an internal review board-approved protocol, pregnant women were referred for magnetic resonance imaging (MRI) after sonographic diagnosis of VM and classified into one of four diagnostic groups: Group 1, normal central nervous system (CNS); Group 2, isolated mild VM (10-12 mm); Group 3, isolated VM > 12 mm; and Group 4, other CNS findings. Pregnancy outcome was obtained. Follow-up visits were offered with assessment of neurodevelopmental, adaptive and neurological functioning at 6 months and 1 year and/or 2 years of age. Atrial diameter and VM group differences in developmental outcomes were evaluated using repeated measures logistic regression and Fishers exact test, respectively. RESULTS: Of 314 fetuses, 253 (81%) were liveborn and survived the neonatal period. Fetuses in Groups 4 and 3 were less likely to progress to live delivery and to survive the neonatal period (60% and 84%, respectively) than were those in Groups 2 or 1 (93% and 100%, respectively, P < 0.001). Of the 143 fetuses followed postnatally, between 41% and 61% had a Bayley Scales of Infant Development (BSID-II) psychomotor developmental index score in the delayed range (< 85) at the follow-up visits, whereas the BSID-II mental developmental index and Vineland Adaptive Behavior composite scores were generally in line with normative expectations. Among those that were liveborn, neither VM group nor prenatal atrial diameter was related to postnatal developmental outcome. CONCLUSIONS: Diagnostic category and degree of fetal VM based on ultrasound and MRI measurements are associated with the incidence of live births and thus abnormal outcome. Among those undergoing formal postnatal testing, VM grade is not associated with postnatal developmental outcome, but motor functioning is more delayed than is cognitive or adaptive functioning.

Cerebellar cleft: confirmation of the neuroimaging pattern.

We recently described the neuroimaging and clinical findings in 6 children with cerebellar clefts and proposed that they result from disruptive changes following prenatal cerebellar hemorrhage. We now report an additional series of 9 patients analyzing the clinical and neuroimaging findings. The clefts were located in the left cerebellar hemisphere in 5 cases, in the right in 3, and bilaterally in one child who had bilateral cerebellar hemorrhages as a preterm infant at 30 weeks gestation. In one patient born at 24 weeks of gestation a unilateral cerebellar hemorrhage has been found at the age of 4 months. Other findings included disordered alignment of the folia and fissures, an irregular gray/white matter junction, and abnormal arborization of the white matter in all cases. Supratentorial abnormalities were found in 4 cases. All but 2 patients were born at term. We confirm the distinct neuroimaging pattern of cerebellar clefts. Considering the documented fetal cerebellar hemorrhage in our first series, we postulate that cerebellar clefts usually represent residual disruptive changes after a prenatal cerebellar hemorrhage. Exceptionally, as now documented in 2 patients, cerebellar clefts can be found after neonatal cerebellar hemorrhages in preterm infants. The short-term outcome in these children was variable.

Suppressor of fused links fused and Cubitus interruptus on the hedgehog signalling pathway.

The Hedgehog (Hh) family of signalling proteins [1] mediate inductive interactions either directly or by controlling the transcription of other secreted proteins through the action of Gli transcription factors, such as Cubitus interruptus (Ci) [2]. In Drosophila, the transcription of Hh targets requires the activation of the protein kinase Fused (Fu) and the inactivation of both Suppressor of fused (Su(fu)) and Costal-2 (Cos-2) [3]. Fu is required for Hh signalling in the embryo and in the wing imaginal disc and acts also as an antitumorigen in ovaries [4]. All fu- phenotypes are suppressed by the loss of function of Su(fu) [5]. Fu, Cos-2 and Ci are co-associated in vivo in large complexes that are bound to microtubules in a Hh-dependent manner [6,7]. Here we investigate the role of Su(fu) in the intracellular part of the Hh signalling pathway. Using the yeast two-hybrid method and an in vitro binding assay, we show that Su(fu), Ci and Fu can interact directly to form a trimolecular complex, with Su(fu) binding to both its partners simultaneously. Su(fu) and Ci also co-immunoprecipitate from embryo extracts. We propose that, in the absence of Hh signalling, Su(fu) inhibits Ci by binding to it and that, upon reception of the Hh signal, Fu is activated and counteracts Su(fu), leading to the activation of Ci.

Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of demodectic mange in dogs.

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against demodectic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and individually housed. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20mg/kg of each of metaflumizone and amitraz, 0.133ml/kg) on Days 0, 28, and 56. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28, 42, 56, and 70. Mite numbers were estimated from skin scrapings taken on Days -3 to -1, 28, 56, and 84. Clinical signs of mange and the extent of demodectic lesions on each dog were evaluated when skin scrapings were conducted. Efficacy of the treatment was based on a reduction in mite numbers and an assessment of the clinical signs associated with canine demodectic mange. Treatment at monthly or two-weekly intervals for 3 months resulted in a rapid reduction in mite numbers (>94 and >99% for the monthly and two-weekly treatments, respectively) and an improvement in clinical signs. Success rates, based on zero mite counts in skin scrapings at Day 84 were 42.9 and 62.5% of dogs for the monthly and two-weekly regimens, respectively.

Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of sarcoptic mange in dogs.

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against sarcoptic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and were housed individually. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20mg/kg of each of metaflumizone and amitraz, at a dose volume of 0.133ml/kg) on Days 0 and 28. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28 and 42. To enumerate Sarcoptes scabiei mites, skin scrapings were taken on each of Days 2, 14, 28, 42 and 56. Clinical signs of mange and the extent of sarcoptic lesions were evaluated on each dog when scrapings were made. Evaluation of the efficacy of the treatment was based on the absence of mites supported by the absence of clinical signs associated with canine sarcoptic mange. Treatment with metaflumizone plus amitraz at the minimum proposed dose rate at monthly (two treatments) or two-weekly (four treatments) intervals resulted in a rapid reduction of mites and improved clinical signs. The overall cure rates at Day 56, based on zero mite counts and/or resolution of clinical signs were 75% and 83% of dogs for the monthly and two-weekly regimens, respectively.

Identification of QRS complex in non-stationary electrocardiogram of sick infants.

BACKGROUND: Due to the high-frequency of routine interventions in an intensive care setting, electrocardiogram (ECG) recordings from sick infants are highly non-stationary, with recurrent changes in the baseline, alterations in the morphology of the waveform, and attenuations of the signal strength. Current methods lack reliability in identifying QRS complexes (a marker of individual cardiac cycles) in the non-stationary ECG. In the current study we address this problem by proposing a novel approach to QRS complex identification. METHOD: Our approach employs lowpass filtering, half-wave rectification, and the use of instantaneous Hilbert phase to identify QRS complexes in the ECG. We demonstrate the application of this method using ECG recordings from eight preterm infants undergoing intensive care, as well as from 18 normal adult volunteers available via a public database. We compared our approach to the commonly used approaches including Pan and Tompkins (PT), gqrs, wavedet, and wqrs for identifying QRS complexes and then compared each with manually identified QRS complexes. RESULTS: For preterm infants, a comparison between the QRS complexes identified by our approach and those identified through manual annotations yielded sensitivity and positive predictive values of 99% and 99.91%, respectively. The comparison metrics for each method are as follows: PT (sensitivity: 84.49%, positive predictive value: 99.88%), gqrs (85.25%, 99.49%), wavedet (95.24%, 99.86%), and wqrs (96.99%, 96.55%). Thus, the sensitivity values of the four methods previously described, are lower than the sensitivity of the method we propose; however, the positive predictive values of these other approaches is comparable to those of our method, with the exception of the wqrs approach, which yielded a slightly lower value. For adult ECG, our approach yielded a sensitivity of 99.78%, whereas PT yielded 99.79%. The positive predictive value was 99.42% for both our approach as well as for PT. CONCLUSIONS: We propose a novel method for identifying QRS complexes that outperforms common currently available tools for non-stationary ECG data in infants. For stationary ECG our proposed approach and the PT approach perform equally well. The ECG acquired in a clinical environment may be prone to issues related to non-stationarity, especially in critically ill patients. The approach proposed in this report offers superior reliability in these scenarios.

Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy.

OBJECTIVE: To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1ß, TNF-α, IFN-λ) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21). The following HRV metrics were quantified in the time domain: alpha_S, alpha_L, root mean square (RMS) at short time scales (RMS_S), RMS at long time scales (RMS_L), while low-frequency power (LF) and high-frequency power (HF) were quantified in the frequency domain. The relationships between HRV metrics and cytokines were evaluated using mixed-models. RESULT: IL-6, IL-8, IL-10, and IL-13 levels were inversely related to selected HRV metrics. CONCLUSION: Inflammation-modulating cytokines may be important mediators in the autonomic dysfunction observed in newborns with HIE.

Cerebral modulation of the autonomic nervous system in term infants.

OBJECTIVE: Central topography of autonomic nervous system (ANS) function has yet to be fully deciphered. In adults it has been shown to lateralize sympathetic and parasympathetic influence predominantly to the right and left cerebral hemispheres, respectively. We examined functional topography of central ANS in newborn subjects utilizing spectral analysis of heart rate variability (HRV), an established measure of ANS function. STUDY DESIGN: We studied newborns with hypoxic-ischemic encephalopathy participating in a prospective study undergoing a therapeutic hypothermia protocol.We included subjects with continuous heart rate data over the first 3 h of normothermia (post rewarming) and brain magnetic resonance imaging, which was reviewed and scored according to a 4 region scheme. HRV was evaluated by spectral analysis in the low-frequency (0.05 to 0.25 Hz) and high-frequency (0.3 to 1 Hz) ranges. The relationship between injured brain regions and HRV was studied using multiple regressions. RESULTS: Forty eight newborns were included. When examined in isolation, right hemisphere injury had a significant negative effect on HRV (-0.088; 95% CI: -0.225,-0.008). The combination of posterior fossa region injury with right hemispheric injury or left hemispheric injury demonstrated significant positive (0.299; 95% CI: 0.065, 0.518) and negative (-0.475; 95% CI: -0.852, -0.128) influences on HRV, respectively. The association between brain injury location and HRV in the high-frequency range did not reach significance. CONCLUSION: Our data support the notion that lateralized cerebral modulation of the ANS, specifically of its sympathetic component, is present in the term newborn, and suggest complex modulation of these tracts by components of the posterior fossa.

Elucidating Metabolic Maturation in the Healthy Fetal Brain Using 1H-MR Spectroscopy.

BACKGROUND AND PURPOSE: (1)H-MRS provides a noninvasive way to study fetal brain maturation at the biochemical level. The purpose of this study was to characterize in vivo metabolic maturation in the healthy fetal brain during the second and third trimester using (1)H-MRS. MATERIALS AND METHODS: Healthy pregnant volunteers between 18 and 40 weeks gestational age underwent single voxel (1)H-MRS. MR spectra were retrospectively corrected for motion-induced artifacts and quantified using LCModel. Linear regression was used to examine the relationship between absolute metabolite concentrations and ratios of total NAA, Cr, and Cho to total Cho and total Cr and gestational age. RESULTS: Two hundred four spectra were acquired from 129 pregnant women at mean gestational age of 30.63 ± 6 weeks. Total Cho remained relatively stable across the gestational age (r(2) = 0.04, P = .01). Both total Cr (r(2) = 0.60, P < .0001) as well as total NAA and total NAA to total Cho (r(2) = 0.58, P < .0001) increased significantly between 18 and 40 weeks, whereas total NAA to total Cr exhibited a slower increase (r(2) = 0.12, P < .0001). Total Cr to total Cho also increased (r(2) = 0.53, P < .0001), whereas total Cho to total Cr decreased (r(2) = 0.52, P < .0001) with gestational age. The cohort was also stratified into those that underwent MRS in the second and third trimesters and analyzed separately. CONCLUSIONS: We characterized metabolic changes in the normal fetal brain during the second and third trimesters of pregnancy and derived normative metabolic indices. These reference values can be used to study metabolic maturation of the fetal brain in vivo.

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

BACKGROUND AND PURPOSE: Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MATERIALS AND METHODS: MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. RESULTS: Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. CONCLUSIONS: Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery.

EEG maturation and stability of cerebral oxygen extraction in very low birth weight infants.

OBJECTIVE: Fractional cerebral tissue oxygen extraction (FTOE) can be continuously monitored by simultaneous near-infrared spectroscopy (NIRS) and pulse oximetry. The objective of this study is to test the hypothesis that in very low birth weight (VLBW) infants, the more mature EEG activity is, the less variable FTOE is. STUDY DESIGN: A prospective study was conducted on VLBW infants (< 1500 g and ⩽ 34 weeks gestation) without significant brain injury. Simultaneous continuous two-channel electroencephalography (EEG), NIRS and pulse oximetry were recorded. Absolute and relative powers of EEG in the delta, theta, alpha, beta and total frequency bands have been calculated. FTOE variability was calculated on two scales: short scales (3 to 20 s) and long scales (20 to 150 s). FTOE variability was examined against changes in relative spectral power of different EEG bands. RESULT: We evaluated 67 studies performed on 46 VLBW infants. Average study duration was 21.3 ± 5.5 h. Relative power of delta band positively correlated with FTOE short- and long-scale variability (r=0.45, P<0.001; r=0.44, P<0.001, respectively). Relative power of alpha bands negatively correlated with FTOE short- and long-scale variability (r=-0.38, P=0.002; r=-0.42, P<0.001, respectively). These correlations continued to be significant when controlling for sex, small for gestational age, postmenstrual age, being on respiratory support, hemoglobin concentration, systemic oxygen saturation and transcutaneous carbon dioxide tension. CONCLUSION: Increased maturation of EEG activity is associated with decreased variability in cerebral oxygen extraction. The implications of increased variability in FTOE on brain injury in premature infants need further exploration.

Site-specific recombination determined by I-SceI, a mitochondrial group I intron-encoded endonuclease expressed in the yeast nucleus.

The Saccharomyces cerevisiae mitochondrial endonuclease I-SceI creates a double-strand break as the initiating step in the gene conversional transfer of the omega+ intron to omega- DNA. We have expressed a galactose-inducible synthetic I-SceI gene in the nucleus of yeast that also carries the I-SceI recognition site on a plasmid substrate. We find that the galactose-induced I-SceI protein can be active in the nucleus and efficiently catalyze recombination. With a target plasmid containing direct repeats of the Escherichia coli lacZ gene, one copy of which is interrupted by a 24-bp cutting site, galactose induction produces both deletions and gene conversions. Both the kinetics and the proportion of deletions and gene conversions are very similar to analogous events initiated by a galactose-inducible HO endonuclease gene. We also find that, in a rad52 mutant strain, the repair of double-strand breaks initiated by I-SceI and by HO are similarly affected: the formation of deletions is reduced, but not eliminated. Altogether, these results suggest either that the two endonucleases act in the same way after double-strand break formation or that the two endonucleases are not involved in subsequent steps.

Squamous carcinoma arising from a true tracheal bronchus: Management and case report.

A case of a squamous carcinoma arising in a "True" tracheal bronchus is described. The presentation and management of this case is discussed.