Spectroscopic gas detection using a Bragg grating - stabilized external cavity laser, custom written in planar integrated silica-on-silicon.

We present the development of an external cavity Bragg grating stabilized laser for tunable diode laser spectroscopy (TDLS). Our design uses a planar integrated silica-on-silicon platform incorporating a custom written Bragg grating as the wavelength-selective element of the laser cavity. We have developed a prototype singlemode laser at 1651 nm and performed a detailed characterization of its performance for the purpose of spectroscopic measurement of methane at this wavelength using a 25 cm path-length single-pass cell. Mode hop-free tuning of 0.13 nm has been demonstrated at frequencies of up to 10 kHz. A single-point limit of detection for TDLS of ΔI/I0 = 8.3 × 10-5 AU was achieved, which is consistent with the performance of standard distributed feedback lasers. The new device exhibits a side-mode suppression ratio of -40 dB and a low RIN of <-150 dB/Hz, and thus avoids the high levels of noise or instability normally associated with larger, mechanically driven external cavity lasers. The silica-on-silicon platform has the potential for low-volume manufacturing of special lasers at the custom wavelengths required for gas detection, without the need for investment in foundry solutions.

Perioperative thrombocytopenia: evidence, evaluation, and emerging therapies.

Thrombocytopenia is a common perioperative clinical problem. While global haemostasis is influenced by many patient- and procedure-related factors, the contribution of thrombocytopenia to bleeding risk is difficult to predict, as platelet count does not linearly correlate with likelihood of bleeding. Thus, the widely used definition of thrombocytopenia and grading of its severity have limited clinical utility. We present a summary and analysis of the current recommendations for invasive procedures in thrombocytopenic patients, although the platelet count at which any given procedure may safely proceed is unknown. The benefits and risks of preoperative platelet transfusions should be assessed on a patient-by-patient basis, and alternatives to platelet transfusion should be considered. In non-emergent surgeries or in postoperative thrombocytopenic patients, haematology consultation should be considered to guide diagnostics and management. We present a pragmatic approach to the evaluation of perioperative thrombocytopenia.

Multifaceted roles of GSK-3 and Wnt/ß-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.

Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/ß-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets.

Developmental coordination disorder at 8 years of age in a regional cohort of extremely-low-birthweight or very preterm infants.

The aims of this study were to determine the motor outcome of extremely-low-birthweight (ELBW; <1000g) or very preterm (<28wks) children compared with normal birthweight (NBW) children, to establish the perinatal associations of developmental coordination disorder (DCD) and its cognitive and behavioural consequences. Participants were consecutive surviving ELBW or very preterm children and randomly selected NBW(>2499g) children born in the state of Victoria, Australia, in 1991 or 1992. Main outcomes were: (1) results of the Movement Assessment Battery for Children (MABC) at 8 years of age; (2) cognitive function; (3) academic progress; and (4) behaviour. Of 298 consecutive ELBW/very preterm survivors, 255 (85.6%; 117 males, 138 females) had the MABC at a mean age of 8 years 8 months. More ELBW/very preterm children (9.5%) had DCD than the NBW group (2%, p=0.001). Only male sex increased the likelihood of DCD in ELBW/very preterm children (p=0.017). ELBW/very preterm children with DCD had worse cognitive function and academic test scores (up to 1SD below those without DCD); they also had more adaptive behaviour and externalizing problems, but not internalizing problems. DCD is more common in ELBW/very preterm children, has few perinatal correlates, and is associated with poor cognitive and academic performance as well as increased behaviour problems.

Extremely low birth weight and body size in early adulthood.

AIMS: To determine the body size of extremely low birth weight (ELBW, birth weight 500-999 g) subjects in early adulthood. METHODS: Cohort study examining the height and weight of 42 ELBW survivors free of cerebral palsy between birth and 20 years of age. Weight and height measurements were converted to Z (SD) scores. RESULTS: At birth the subjects had weight Z scores substantially below zero (mean birth weight Z score -0.90, 95% CI -1.25 to -0.54), and had been lighter than average at ages 2, 5, and 8 years. However, by 14, and again at 20 years of age their weight Z scores were not significantly different from zero. At ages 2, 5, 8, 14, and 20 years of age their height Z scores were significantly below zero. Their height at 20 years of age was, however, consistent with their parents' height. As a group they were relatively heavy for their height and their mean body mass index (BMI) Z score was almost significantly different from zero (mean difference 0.42, 95% CI -0.02 to 0.84). Their mean BMI (kg/m2) was 24.0 (SD 5.2); 14 had a BMI >25, and four had a BMI >30. CONCLUSIONS: Despite their early small size, by early adulthood the ELBW subjects had attained an average weight, and their height was consistent with their parents' height. They were, however, relatively heavy for their height.

An assessment of water quality, physical habitat, and biological integrity of an urban stream in Wichita, Kansas, prior to restoration improvements (phase I).

Urban development alters the natural hydrological conditions of many streams and rivers often resulting in the degradation of water quality, physical habitat, and biotic integrity of lotic systems. Restoration projects attempt to improve and maintain the ecological integrity of urban streams; however, few projects have quantified improvements to stream ecology following implementation of restoration measures. This paper summarizes pre-restoration data collected as part of an urban stream restoration project on Gypsum Creek in Wichita, Kansas. Water quality monitoring revealed eutrophic conditions in the stream and the presence of pesticides. Channelization has led to changes in physical habitat including bank erosion, sedimentation, loss of substrate and channel diversity, elimination of in-stream aquatic habitat, removal of riparian vegetation, and decreased base flows. Benthic macroinvertebrate communities appear degraded with more than 90% of individuals collected described as tolerant to anthropogenic stressors. Fish communities were assessed with an Index of Biotic Integrity and were rated as poor to fair, with trophic structure dominated by generalists, no sensitive species present, and one-third of the species collected considered non-native. Overall, the data collected strongly suggest that site-specific restoration measures need to be implemented in order to improve and maintain the ecological condition of Gypsum Creek. Recommendations for improvements have been made to city managers, with implementation beginning in spring 2003 (dependent upon funding availability).

Cloning and expression of a novel cysteine-rich secreted protein family member expressed in thyroid and pancreatic mesoderm within the chicken embryo.

We have isolated a new chicken gene that is a member of the cysteine-rich secreted protein family (CRISP). The CRISP family is composed of over 70 members that are found in many phyla of organisms, including: vertebrates, plants, fungi, yeast, and insects. Here we describe the cloning of a novel member of this family, SugarCrisp, and its expression pattern throughout chicken embryogenesis. We also describe its utility as a marker of thyroid and pancreatic mesoderm in the developing chicken embryo and its expression within the human and mouse in glandular tissue.

Auditory function at 14 years of age of very-low-birthweight.

The aim of the study was to determine audiological function at 14 years of age of very-low-birthweight (VLBW < or = 1500 g) children compared with a cohort of normal birthweight (NBW > 2499 g) children. Participants were consecutive surviving preterm children of birthweight < 1000 g born between 1977 and 1982 (n=86) and of birthweight 1000 to 1500 g born between 1980 and 1982 (n=124) and randomly selected NBW children born between 1981 and 1982 (n=60). Audiometric tests included pure tone audiometry, tympanometry, stapedius muscle reflexes, and measures of central auditory processing. Psychometric tests included measures of IQ, academic achievement, and behaviour. There were no significant differences in rates of hearing impairment, abnormal tympanograms, figure-ground problems, or digit recall between VLBW children and NBW control children. VLBW children had higher rates of some central auditory processing problems, which in turn were associated with poorer intellectual, academic, and behavioural progress.

Birth weight <1501 g and respiratory health at age 14.

AIMS: To determine the respiratory health in adolescence of children of birth weight <1501 g, and to compare the results with normal birthweight controls. METHODS: Prospective cohort study of children born in the Royal Women's Hospital, Melbourne. Two cohorts of preterm children (86 consecutive survivors 500-999 g birth weight, and 124 consecutive survivors 1000-1500 g birth weight) and a control group of 60 randomly selected children >2499 g birth weight were studied. Children were assessed at 14 years of age. A paediatrician determined the clinical respiratory status. Lung function was measured according to standard guidelines. RESULTS: Of 180 preterm children seen at age 14, 42 (23%) had bronchopulmonary dysplasia (BPD) in the newborn period. Readmission to hospital for respiratory ill health was infrequent in all groups and the rates of asthma were similar (15% in the 500-999 g birth weight group, 21% in the 1000-1500 g birth weight group, 21% in controls; 19% BPD, 18% no BPD). Overall, lung function was mostly within the normal range for all cohorts; few children had lung function abnormalities in clinically significant ranges. However, the preterm children had significantly lower values for variables reflecting flow. Lung function in children of 500-999 g birth weight was similar to children of 1000-1500 g birth weight. Preterm children with BPD had significantly lower values for variables reflecting flow than children without BPD. CONCLUSIONS: The respiratory health of children of birth weight <1501 g at 14 years of age is comparable to that of term controls.

Very low birth weight and growth into adolescence.

OBJECTIVE: To compare the growth and pubertal development of very low-birth-weight (VLBW) children (birth weight <1500 g) and normal-birth-weight (NBW) children (birth weight >2499 g) to adolescence to determine if, and at what age, VLBW children "catch up." DESIGN: Inception cohort study to age 14 years. SETTING: Royal Women's Hospital, Melbourne, Australia. PATIENTS: Eighty-six consecutive survivors with a birth weight less than 1000 g, 120 consecutive survivors with a birth weight of 1000 to 1499 g, and 60 randomly selected NBW controls. Children with cerebral palsy at age 14 years were excluded. MAIN OUTCOME MEASURES: Weight, height, and head circumference measurements at birth and ages 2, 5, 8, and 14 years converted to z (SD) scores. RESULTS: At age 14 years, pubertal development was similar in NBW and VLBW children. At ages 2, 5, 8, and 14 years, VLBW children were significantly shorter and lighter and had smaller head circumferences than NBW children. The differences in height and weight between VLBW and NBW children were less apparent as SD scores improved in VLBW children over time. Within the VLBW group, compared with children with a birth weight of 1000 to 1499 g, those with a birth weight less than 1000 g had significantly lower weight z scores earlier in childhood but not at age 14 years, significantly lower height z scores only at age 2 years, and significantly lower head circumference z scores throughout childhood. CONCLUSION: This group of VLBW children experienced late catch-up growth to age 14 years but remain smaller than their NBW peers. Arch Pediatr Adolesc Med. 2000;154:778-784

Antenatal corticosteroids and outcome at 14 years of age in children with birth weight less than 1501 grams.

OBJECTIVE: To determine whether exposure to antenatal corticosteroid therapy was associated with adverse effects on growth, sensorineural outcome, or lung function of children of birth weight <1501 g at 14 years of age. DESIGN: Cohort study. SETTING: The Royal Women's Hospital, Melbourne, Australia. SUBJECTS: One hundred fifty-four consecutive survivors born from October 1, 1980 to March 31, 1982. INTERVENTIONS: The mothers of 78 survivors (51%) had been given corticosteroids antenatally to accelerate fetal lung maturation. Treatment with antenatal corticosteroids was nonrandom. No mother received >1 course of corticosteroids. OUTCOME MEASURES: The children were assessed at 14 years of age, corrected for prematurity. All assessors were unaware of the exposure of the child to antenatal corticosteroids. The assessments included measurements of growth and neurological, cognitive, and lung function. Growth measurements were converted into z scores (standard deviation) for the appropriate age and gender. RESULTS: Of the 154 survivors, 130 (84%) were assessed at 14 years of age. Overall, the children exposed to antenatal corticosteroids were significantly taller (height z score; mean difference:.39; 95% confidence interval:.001-. 79) and had better cognitive functioning (Wechsler Intelligence Scale for Children-Third Edition Full Scale; IQ mean difference: 6. 2; 95% confidence interval:.8-11.6) than those not exposed to corticosteroids. There were no other differences in sensorineural outcomes between the groups. Lung function was not significantly different between the groups. No conclusions were altered by adjustment for confounding variables. CONCLUSIONS: Exposure to 1 course of antenatal corticosteroid therapy was associated with some clinically and statistically improved outcomes at 14 years of age in children of birth weight <1501 g, with no obvious adverse effects on growth or on sensorineural, cognitive, or lung function. corticosteroids, growth, cognitive, IQ, lung function, adolescence.

Survival, cranial ultrasound and cerebral palsy in very low birthweight infants: 1980s versus 1990s.

OBJECTIVE: To determine the changes in the rates of survival, cranial ultrasound abnormalities and cerebral palsy in very low birthweight (VLBW) (birthweight 500-1499 g) infants between the early 1980s and the early 1990s. METHODOLOGY: A cohort study of consecutive VLBW live births in one tertiary perinatal hospital during two distinct eras was performed at The Royal Women's Hospital, Melbourne, a level-III perinatal centre. Consecutive VLBW infants born over the 18-month period from 1 October 1980 (n = 222), and over the 12-month period from 1 January 1992 (n = 202) were identified. The main outcome measures were the proportions of live births surviving to 5 years of age, rates of cranial ultrasound abnormalities, and rates of cerebral palsy at 5 years of age. RESULTS: Over the 18 months from 1 October 1980, 68% (150/222) VLBW live births survived to 5 years of age. The survival rate rose substantially to 82% (165/202) during 1992 (odds ratio 2.1, 95% confidence interval 1.4-3.2). The survival rate increased over time more for those of 500-999 g birthweight than for those of 1000-1499 g birthweight. The rates of cerebroventricular haemorrhage (CVH) were similar inlive births and survivors from both eras, as were the rates of cerebral palsy (7.5% in 1980-82; 7.8% in 1992) in survivors seen at 5 years of age. The positive predictive value of CVH for cerebral palsy was low, but cystic periventricular leucomalacia was followed by cerebral palsy in seven of eight survivors from the 1992 cohort. CONCLUSIONS: Despite the increasing survival rate with improvements in perinatal care, including more antenatal steroid therapy and the introduction of exogenous surfactant, the rates of CVH and of cerebral palsy in survivors have not diminished.

Methylxanthines and sensorineural outcome at 14 years in children < 1501 g birthweight.

OBJECTIVES: Methylxanthines, including theophylline, have been used extensively and successfully to treat apnoea in preterm infants. However, long-term consequences of such therapy are largely unknown. The aim of this study was to determine the relationship between theophylline therapy and outcome at 14 years of age in surviving preterm children of birthweight < 1501 g. METHODOLOGY: The subjects of this study were 154 consecutive survivors with birthweights < 1501 g born from 1 October 1980 to 31 March 1982; 130 (84.4%) were assessed at 14 years of age. Outcomes included motor function, psychological test scores, and growth. RESULTS: Of the 130 children assessed, 69 (53.1%) had been exposed to theophylline; 13.0% had cerebral palsy, significantly higher than 1.6% in the 61 children not exposed to theophylline (P < 0.02). This difference remained statistically significant after adjusting for potential confounding variables including the presence of cerebroventricular haemorrhage. In contrast, after adjusting for known confounding variables, children who had received theophylline achieved higher psychological test scores. There was no association between theophylline therapy and growth. CONCLUSIONS: Theophylline therapy in the newborn period is associated with some evidence of harmful, but also helpful sensorineural effects at 14 years of age.

Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children.

Antenatal corticosteroid therapy substantially improves the survival rate of preterm infants, with few side effects. Higher blood pressure in adulthood has been described in several animal species after exposure to antenatal corticosteroids, but there are no similar reports in humans. The objective of the present study was to determine the relationship between exposure to antenatal corticosteroid therapy and blood pressure at 14 years of age. This was a cohort study of 210 preterm survivors with birthweights of <1501 g born in the Royal Women's Hospital, Melbourne, between 1 January 1977 and 31 March 1982. Blood pressure was measured in 177 subjects (84.3%) at 14 years of age with a standard mercury sphygmomanometer. Children exposed to antenatal corticosteroids (n=89) had higher systolic and diastolic blood pressures than those not exposed to corticosteroids (n=88) [mean difference (95% confidence interval) (mmHg): systolic, 4.1 (0.1-8.0); diastolic, 2.8 (0.05-5.6)]. However, few had blood pressure in the hypertensive range. It is concluded that antenatal corticosteroid therapy is associated with higher systolic and diastolic blood pressures in adolescence, and might lead to clinical hypertension in survivors well beyond birth.

Changes in lung function between age 8 and 14 years in children with birth weight of less than 1,501 g.

We set out to determine whether lung function of children with a birth weight of <1,501 g changed relative to expectations between the ages of 8 and 14 years. We hypothesized that changes in lung function may differ between those of birth weight above and below 1,000 g. The subjects of this study were born in the Royal Women's Hospital, Melbourne. There were 86 consecutive survivors with birth weights <1,000 g born between January 1, 1977 and March 31, 1982, and 124 consecutive survivors with birth weights 1,000-1,500 g born between October 1, 1980 and March 31, 1982. Lung function was measured at both age 8 and 14 years, corrected for prematurity in 78% (67/86) of those with birth weight <1,000 g, and in 69% (86/124) of those with birth weight 1,000-1,500 g. Overall, lung function was similar to predicted values at both 8 and 14 years of age [e.g., (forced expired volume in 1 s, FEV1% predicted) at age 8 years mean 88.5% (SD 14.7) and at age 14 years, mean 94.9% (SD 13.8)]. There were significant changes, mostly improvements, in lung function between age 8-14 years relative to predicted values: FEV1 (% predicted) increased between 8-14 years of age by a mean of 6.4 (95% confidence interval, 4.4-8.3). The improvements in some lung function variables were significantly greater in those of birth weight <1,000 g compared with those of birth weight 1,000-1,500 g: improvement in FEV1 (% predicted) between age 8-14 years in infants with birth weight <1,000 g had a mean of 10.3 (SD 13.1), and in those with birthweight 1,000-1,500 g a mean of 3.3 (SD 10.1). We conclude that lung function improved significantly relative to predicted values in children of birth weight <1,501 g between age 8-14 years. The improvements were greatest in those of birth weight <1,000 g.

Aberrant splicing of a mouse disabled homolog, mdab1, in the scrambler mouse.

Although accurate long-distance neuronal migration is a cardinal feature of cerebral cortical development, little is known about control of this migration. The scrambler (scm) mouse shows abnormal cortical lamination that is indistinguishable from reeler. Genetic and physical mapping of scm identified yeast artificial chromosomes containing an exon of mdab1, a homolog of Drosophila disabled, which encodes a phosphoprotein that binds nonreceptor tyrosine kinases. mdab1 transcripts showed abnormal splicing in scm homozygotes, with 1.5 kb of intracisternal A particle retrotransposon sequence inserted into the mdab1 coding region in antisense orientation, producing a mutated and truncated predicted protein. Therefore, mdab1 is most likely the scm gene, thus implicating nonreceptor tyrosine kinases in neuronal migration and lamination in developing cerebral cortex.

Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain.

The Pax-6 gene encodes a transcription factor that is expressed in regionally restricted patterns in the developing brain and eye. Here we describe Pax-6 expression in the early forebrain (prosencephalon) on embryonic day 9.5 (E9.5) to E10.5 using both whole-mount in situ hybridization and antibody labeling. We find close correlations between Pax-6+ domains and initial neural patterning, and identify corresponding defects in embryos homozygous for the Pax-6 allele, Small eye (Sey). Pax-6 expression defines the prosencephalon-mesencephalon boundary, and mutant embryos lack this morphological boundary. Markers of the caudal prosencephalon are lost (Pax-6, Lim-1, Gsh-1) and a marker for mesencephalon is expanded rostrally into the prosencephalon (Dbx). We conclude that the caudal prosencephalon (prosomere 1) is at least partially transformed to a mesencephalic fate. This transformation results in a specific deficit of posterior commissure axons. Sey/Sey embryos also exhibit an axon pathfinding defect specific to the first longitudinal tract in the prosencephalon (tpoc, tract of the postoptic commissure). In wild type, tpoc axons fan out upon coming in contact with a superficial patch of Pax-6+ neuron cell bodies. In the mutant, the tpoc axons have normal initial projections, but make dramatic errors where they contact the neuron cell bodies, and fail to pioneer this first tract. Thus Pax-6 is required for local navigational information used by axons passing through its domain of expression. We conclude that Pax-6 plays multiple roles in forebrain patterning, including boundary formation, regional patterning, neuron specification and axon guidance.

Axon tracts correlate with netrin-1a expression in the zebrafish embryo.

Netrins are secreted molecules that can attract or repel growth cones from a variety of organisms. In order to clarify the extent and scope of the effects of netrins for guiding growth cones, we have analyzed netrin-1a within the relatively simple and well-characterized nervous system of zebrafish embryos. netrin-1a is expressed in dynamic patterns that suggest that it guides the growth cones of a wide variety of neurons. The spatiotemporal relationship of netrin-1a expression and extending growth cones further suggests that netrins may act to delineate specific pathways and stimulate axonal outgrowth in addition to attracting and repelling growth cones. Furthermore, aberrant outgrowth by commissural growth cones in the spinal cords of floating head mutants, in which netrin-1a expression is altered, is consistent with an in vivo, chemoattractive action of netrin-1a. These data suggest that netrins act on many growth cones and influence their behavior in a variety of ways.