Using Ultrathin Parylene Films as an Organic Gate Insulator in Nanowire Field-Effect Transistors.

We report the development of nanowire field-effect transistors featuring an ultrathin parylene film as a polymer gate insulator. The room temperature, gas-phase deposition of parylene is an attractive alternative to oxide insulators prepared at high temperatures using atomic layer deposition. We discuss our custom-built parylene deposition system, which is designed for reliable and controlled deposition of <100 nm thick parylene films on III-V nanowires standing vertically on a growth substrate or horizontally on a device substrate. The former case gives conformally coated nanowires, which we used to produce functional Ω-gate and gate-all-around structures. These give subthreshold swings as low as 140 mV/dec and on/off ratios exceeding 103 at room temperature. For the gate-all-around structure, we developed a novel fabrication strategy that overcomes some of the limitations with previous lateral wrap-gate nanowire transistors. Finally, we show that parylene can be deposited over chemically treated nanowire surfaces, a feature generally not possible with oxides produced by atomic layer deposition due to the surface "self-cleaning" effect. Our results highlight the potential for parylene as an alternative ultrathin insulator in nanoscale electronic devices more broadly, with potential applications extending into nanobioelectronics due to parylene's well-established biocompatible properties.

Maternal and infant factors associated with neonatal adiposity: results from the Tasmanian Infant Health Survey (TIHS).

OBJECTIVE: To examine the maternal and neonatal factors associated with offspring adiposity and the role of birth and placental weight as potential mediators in such associations. DESIGN: The Tasmanian Infant Health Survey was a prospective cohort study conducted between 1988 and 1995 in Australia to investigate the cause of Sudden Infant Death Syndrome. This large infant cohort provides measurement of skinfolds on 7945 mothers and their offspring. SUBJECTS: Participants included singletons born ≥37 weeks gestation who were at high risk of sudden infant death syndrome identified through a composite score that included birth weight, maternal age, neonatal gender, season of birth, duration of second-stage labor and intention to breastfeed. MEASUREMENTS: Neonatal adiposity was assessed from skinfold measurements of the subscapular (SSF) and triceps folds (TSF) taken at birth. Maternal early-pregnancy body mass index (BMI) was calculated from self-reported height and weight. Neonatal data were extracted from birth records. Data relating to other environmental exposures were obtained from questionnaires administered when neonates were ∼4-days old. RESULTS: In multivariable models, higher maternal adiposity, increasing maternal age, gestation age, delivery by Caesarian section and female gender were associated with larger SSF independent of placental and birth weight (P<0.001). Maternal age and delivery by Caesarian section were significantly associated with larger TSF, whereas gestational age and male gender were associated with thinner TSF independent of placental and birth weight. Higher early-pregnancy BMI, maternal weight gain, maternal age, parity and gestational age were significantly associated with larger placental and birth weight. Smoking during pregnancy was associated with smaller birth weight but not with placental weight. CONCLUSION: In addition to birth weight, maternal adiposity and placental weight were important additional factors associated with neonatal adiposity.

An anterior cruciate ligament injury prevention framework: incorporating the recent evidence.

Anterior cruciate ligament (ACL) injury rates have increased by ∼50% over the last 10 years. These figures suggest that ACL focused research has not been effective in reducing injury rates among community level athletes. Training protocols designed to reduce ACL injury rates have been both effective (n = 3) and ineffective (n = 7). Although a rationale for the use of exercise to reduce ACL injuries is established, the mechanisms by which they act are relatively unknown. This article provides an injury prevention framework specific to noncontact ACL injuries and the design of prophylactic training protocols. It is also apparent that feedback within this framework is needed to determine how biomechanically relevant risk factors like peak joint loading and muscular support are influenced following training. It is by identifying these links that more effective ACL injury prevention training programs can be developed, and, in turn, lead to reduced ACL injury rates in the future.

Maternal antenatal peanut consumption and peanut and rye sensitization in the offspring at adolescence.

BACKGROUND: There is considerable controversy whether maternal peanut ingestion during pregnancy might influence sensitization in later life. Objective To examine whether maternal peanut ingestion during pregnancy might increase sensitization in the offspring. METHODS: A population-based longitudinal cohort study with 16 years follow-up was conducted (N=373). Subjects were recruited at birth as part of an infant health study. Maternal antenatal peanut consumption was documented at birth and peanut and rye sensitization were determined by measurement of serum-specific IgE at age 16. RESULTS: Peanut sensitization was common (14%). In the entire cohort (n=310), there was no association between antenatal peanut ingestion and peanut sensitization (P=0.17). However, there was a strong association between antenatal peanut ingestion and decreased risk of rye sensitization and peanut sensitization in those (n=201) without a family history (FH) of asthma (Rye OR 0.30, 95% CI 0.14-0.63, P=0.001 and Peanut OR 0.18, 95% CI 0.04-0.78, P=0.02). There was an increased risk of rye sensitization in those (n=108) with a FH of asthma and antenatal peanut ingestion (Rye OR 2.69, 95% CI 1.11-6.51 P=0.03). It was considered that these sensitizations were likely to be related to the presence of IgE antibodies to cross-reacting carbohydrate epitopes common to rye and peanut allergens. CONCLUSIONS AND CLINICAL RELEVANCE: Antenatal peanut ingestion may influence the development of IgE antibody to cross-reacting carbohydrate epitopes in later life. Genetic factors may modify this association.

Electronic transport in conducting polymer nanowire array devices.

We report on the temperature dependent conductivity and current-voltage (I-V) properties of novel polyaniline nanowire array devices. Below 60 K, I-V measurements show a transition to non-linear behaviour, leading to the onset at 30 K of a threshold voltage, for potentials below which little current flows. By considering an intrinsic morphology of small conducting regions separated by tunnel junctions, we show that charging of the conducting regions leads to Coulomb blockade effects that can account for this behaviour.

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial.

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Recovery of threatened plant species and their habitats in the biodiversity hotspot of the Southwest Australian Floristic Region.

The Southwest Australian Floristic Region (SWAFR) is a global biodiversity hotspot with high plant diversity and endemism and a broad range of threatening processes. An outcome of this is a high proportion of rare and threatened plant species. Ongoing discovery and taxonomic description of new species, many of which are rare, increases the challenges for recovery of threatened species and prioritisation of conservation actions. Current conservation of this diverse flora is based on integrated and scientific evidence-based management. Here we present an overview of current approaches to the conservation of threatened flora in the SWAFR with a focus on active management through recovery and restoration that is integrated with targeted research. Key threats include disease, fragmentation, invasive weeds, altered fire regimes, grazing, altered hydro-ecology and climate change. We highlight the integrated approach to management of threats and recovery of species with four case studies of threatened flora recovery projects that illustrate the breadth of interventions ranging from In situ management to conservation reintroductions and restoration of threatened species habitats. Our review and case studies emphasise that despite the scale of the challenge, a scientific understanding of threats and their impacts enables effective conservation actions to arrest decline and enhance recovery of threatened species and habitats.

The association between maternal smoking in pregnancy, other early life characteristics and childhood vision: the Twins Eye Study in Tasmania.

PURPOSE: To investigate the association between maternal smoking in pregnancy, early-life environment and childhood vision. METHODS: Twin and triplet children enrolled in the Twins Eye Study in Tasmania underwent a comprehensive ophthalmic examination and their parents/guardians retrospectively answered a questionnaire regarding crawling, walking and other measures. A subset of these twins was also in the Tasmanian Infant Health Survey, which prospectively collected data on antenatal smoking, gestation, birth weight and other factors. RESULTS: The mean age of the 346 individuals (172 multiple birth sets) at the time of examination was 9.25+/-2.4 years. Mean unaided visual acuity was 0.0 (6/6). The mean spherical equivalent was +0.87D, and decreased with increasing child age (p<0.01). A prospective analysis, accounting for birth set clustering and relevant confounders, showed increasing levels of maternal smoking in the third trimester was associated with poor stereoacuity on the Titmus test (worse (>) than 100'', p=0.05) and Lang test (p=0.001) and also with the presence of esotropia (p=0.02). These associations persisted after adjustment for infant postnatal smoke exposure at one month of age. Poor stereoacuity on Titmus stereo test circles was associated with late age of first crawling (RR=1.23 (1.06, 1.42) p=0.005 per month) and late age of first walking (RR 1.18 (1.05, 1.22) p=0.001 per month). CONCLUSIONS: Antenatal smoking was independently associated with poor stereovision and the presence of esotropia. Poor stereoacuity may be associated with delayed age at first crawling or walking.

Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth.

AIM: A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. DESIGN: We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. RESULTS: In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0; P=0.02). Protein intake was also associated negatively with ponderal index (beta=-0.01; 95% CI: -0.02, -0.00; P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. CONCLUSIONS: This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.

Autologous olfactory ensheathing cell transplantation in human spinal cord injury.

Olfactory ensheathing cells transplanted into the injured spinal cord in animals promote regeneration and remyelination of descending motor pathways through the site of injury and the return of motor functions. In a single-blind, Phase I clinical trial, we aimed to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. Participants were three male paraplegics, 18-55 years of age, with stable, complete thoracic injuries 6-32 months previously, with stable spinal column, no implanted prostheses, and no syrinx. Olfactory ensheathing cells were grown and purified in vitro from nasal biopsies and injected into the region of damaged spinal cord. The trial design includes a matched injury group as a control for the assessors, who are blind to treatment status. Assessments, made before transplantation and at regular intervals subsequently, include MRI, medical, neurological and psychosocial assessments, and standard American Spinal Injury Association and Functional Independence Measure assessments. One year after cell implantation, there were no medical, surgical or other complications to indicate that the procedure is unsafe. There is no evidence of spinal cord damage nor of cyst, syrinx or tumour formation. There was no neuropathic pain reported by the participants, no change in psychosocial status and no evidence of deterioration in neurological status. Participants will be followed for 3 years to confirm long-term safety and to compare neurological, functional and psychosocial outcomes with the control group. We conclude transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to one year post-implantation.

Toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea in human cell lines with different DNA repair phenotypes.

We examined the toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea (ENU) in three Epstein-Barr virus-transformed human lymphoblastoid cell lines, each with a different DNA repair phenotype. One cell line lacks O6-alkylguanine-DNA alkyltransferase (AGT) activity; another, derived from a patient with xeroderma pigmentosum, complementation group A, lacks nucleotide exicision repair (NER) capability, and the third is competent in both repair functions. ENU-induced toxicity and mutagenicity at the hypoxanthine-guanine phosphoribosyltransferase locus were increased to a similar degree relative to the repair-competent cells in both AGT-deficient and NER-deficient cells. We determined the mutational spectra for ENU by identifying DNA sequence changes at the hypoxanthine-guanine phosphoribosyltransferase locus in at least 26 clones resistant to 6-thioguanine from each cell line. Of the characterized mutations, 89% were single-base pair substitutions. Transitions and transversions were found at AT and GC base pairs in all three cell lines. The biggest difference within the spectra was in the rate of transitions at GC base pairs. Compared to the repair-competent cell line, this mutation was elevated about 8-fold in the AGT-deficient cells and about 3-fold in the NER-deficient cells. We conclude that both AGT and NER play an important role in protecting human cells from the toxic and mutagenic effects of ENU. Furthermore, the mutational spectra suggest that both of these repair systems participate in the repair of O6-ethylguanine adducts.

Clonally unrelated BCR-ABL-negative acute myeloblastic leukemia masquerading as blast crisis after busulphan and interferon therapy for BCR-ABL-positive chronic myeloid leukemia.

We report a patient with Philadelphia (Ph)-positive, BCR-ABL rearrangement positive, chronic myeloid leukemia (CML) with a prolonged chronic phase of 24 years who was first prescribed alpha-2 interferon 22 years after initial diagnosis. This therapy was tolerated poorly on account of thrombocytopenia, but an eventual major cytogenetic response was followed soon afterwards by transformation to terminal acute myeloid leukemia (AML). Cytogenetic studies indicated that the transformed myeloblasts were karyotypically normal and Ph negative. Although polymerase chain reaction (PCR) analysis of total leukemic mRNA remained BCR-ABL positive, other molecular studies, including Southern blotting and fluorescent in situ hybridization (FISH) analyses, showed that myeloblasts were BCR-ABL rearrangement negative. PCR-based clonality studies using an X-chromosome-linked restriction fragment polymorphism within the phosphoglycerate kinase gene (PGK1) further showed that the Ph-negative blast cells had a different clonal origin from the Ph-positive clone of chronic phase. We suggest that cases of underlying Ph-negative leukemic transformation in Ph-positive CML warrant further study and should be considered for trial of intensive remission induction therapy as appropriate for acute leukemia.

A doubly responsive probe for the detection of Cys4-tagged proteins.

Recombinant proteins bearing a tag are crucial tools for assessing protein location or function. Small tags such as Cys4 tag (tetracysteine; Cys-Cys-X-X-Cys-Cys) are less likely disrupt protein function in the living cell than green fluorescent protein. Herein we report the first example of the design and synthesis of a dual fluorescence and hyperpolarized (129)Xe NMR-based sensor of Cys4-tagged proteins. This sensor becomes fluorescent when bound to such Cys4-tagged peptides, and the (129)Xe NMR spectrum exhibits a specific signal, characteristic of the biosensor-peptide association.

The Larimer County Children's Clinic. A public-private partnership to provide medical care to indigent children.

OBJECTIVE: To describe a unique collaboration between private and public entities to provide comprehensive health care to medically indigent children in rural Larimer County, Colo. SETTING: The Children's Clinic, Fort Collins, Colo. STUDY PARTICIPANTS: Uninsured children and those eligible for Medicaid, living in families with incomes below 150% of the federal poverty level. SELECTION PROCEDURES: Eligible patients have been enrolled in the Children's Clinic on a first-come, first-served basis. INTERVENTIONS: A community collaboration involving an interactive system with the Children's Clinic staff, the Larimer County Department of Health and Environment, private primary care and subspecialty physicians, ancillary health providers, and the family practice residency program at Poudre Valley Hospital, Fort Collins. Funding for this endeavor has been composed of city and county funds, public and private grants, community business support, and local fund-raising efforts, as well as Medicaid reimbursements. MEASUREMENTS/MAIN RESULTS: Since 1989, comprehensive pediatric care has been provided to a growing number of eligible children. At present, 3619 children, aged birth to 18 years, from 2230 families are being served. From this population, there were 8945 office visits to the Children's Clinic, 1392 patient contacts by the clinic social workers, 1287 visits to the Larimer County Department of Health and Environment for well-child care, 543 referrals to subspecialists and other community health care providers, and 615 after-hours visits to the Poudre Valley Hospital emergency department between July 1, 1992, and June 30, 1993. The clinic's professional staff consists of 2 1/4 full-time pediatric care providers, one nurse, one medical social worker, one receptionist, and one administrator, with an expenditure of $356,471. CONCLUSIONS: The Children's Clinic collaboration has provided comprehensive pediatric health care to a population that previously received only fragmented care. The next step is to assess the impact of this program on the frequency of emergency department visits for these patients.

Computer simulation of O2 transport and utilization mechanisms at the onset of exercise.

During transitions in work rate, O2 uptake (VO2) kinetics at the working tissue level might be rate limited by O2 transport and/or by O2 utilization. A computer model with parallel working and non-working tissue compartments, connected to an ideal lung by a variable-sized venous blood volume, was developed to study this. The time constant for working tissue O2 demand (tau T) was set by a first-order linear metabolic response. The model attempted to replicate the VO2 response at the alveolar level of a single subject performing step transitions on a cycle ergometer from 25 to 105 W [total lag time (equivalent to 63% increase above baseline) = 40.2 s]. Measured cardiac output kinetics (total lag time = 44.1 s) were used as a model parameter. Blood flow to the nonworking tissue (QNW) was kept constant at 4.5 or 5.0 l/min. A critical PO2 of 20 Torr was set, and the Bohr effect on the O2-hemoglobin dissociation curve was included. The "best" simulation had tau T = 36 s, QNW = 4.5 l/min, and venous blood volume = 2 liters and was not O2 transport limited. The approximation to the real data was good in all but the phase 1 response, where the model underpredicted the measured response. However, when QNW was increased to 5.0 l/min, the model was O2 transport limited; yet the predicted VO2 response at the alveolar level was not notably different from the subject's data.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency domain analysis of ventilation and gas exchange kinetics in hypoxic exercise.

The kinetics of O2 up-take (VO2), CO2 output (VCO2), ventilation (VE), and heart rate (HR) were studied during exercise in normoxia and hypoxia [inspired O2 fraction (FIO2) 0.14]. Eight male subjects each completed 6 on- and off-step transitions in work rate (WR) from low (25 W) to moderate (100-125 W) levels and a pseudorandom binary sequence (PRBS) exercise test in which WR was varied between the same WRs. Breath-by-breath data were linearly interpolated to yield 1-s values. After the first PRBS cycle had been omitted as a warm-up, five cycles were ensemble-averaged before frequency domain analysis by standard Fourier methods. The step data were fit by a two-component (three for HR) exponential model to estimate kinetic parameters. In the steady state of low and moderate WRs, each value of VO2, VCO2, VE, and HR was significantly greater during hypoxic than normoxic exercise (P less than 0.05) with the exception of VCO2 (low WR). Hypoxia slowed the kinetics of VO2 and HR in on- and off-step transitions and speeded up the kinetics of VCO2 and VE in the on-transition and of VE in the off-transition. Frequency domain analysis confined to the range of 0.003-0.019 Hz for the PRBS tests indicated reductions in amplitude and greater phase shifts in the hypoxic tests for VO2 and HR at specific frequencies, whereas amplitude tended to be greater with little change in phase shift for VCO2 and VE during hypoxic tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Faster O2 uptake kinetics at onset of supine exercise with than without lower body negative pressure.

The kinetics of oxygen uptake (VO2) were observed at the onset of submaximal cycling exercise in seven men and one woman [mean age 22.6 +/- 0.9 (SE) yr] in the upright and supine positions and the supine position with -40 mmHg lower body negative pressure (LBNP). There was no significant difference for peak VO2 and ventilatory threshold between the supine (3,081 +/- 133 and 1,954 +/- 138 ml/min, respectively) and the supine + LBNP positions (3,062 +/- 152 and 1,973 +/- 122 ml/min); however, both were reduced compared with upright exercise (3,483 +/- 200 and 2,353 +/- 125 ml/min). Kinetic analysis applied to six repetitions by each subject indicated a slowing from a mean total lag time (time required to achieve 63% of the difference in VO2 between baseline and new steady state) of 36.3 +/- 2.7 s in upright exercise to 44.1 +/- 3.5 s in the supine position. However, total lag time for the supine + LBNP position (36.0 +/- 2.8 s) did not differ from upright exercise but was significantly faster than supine exercise. These data have been interpreted in support of an O2 transport limitation to VO2 kinetics at the onset of supine exercise that is countered by LBNP, likely through a more rapid increase in perfusion to the exercising muscle at these submaximal work rates.

Resting metabolic rate is influenced by anxiety in college men.

The effects of psychological parameters on resting metabolic rate (RMR) have been inadequately researched. The purpose of this study was to investigate relationships between anxiety and RMR. Seventy-nine male college students completed the trait portion (form Y-2) of the State-Trait Anxiety Inventory (C. D. Spielberger, R. L. Gorsuch, R. Lushene, P. R. Vagg, and G. A. Jacobs. Self-evaluation questionnaire (form Y). In: Manual for the State-Trait Anxiety Inventory. Palo Alto, CA, Consulting Psychologists Press, 1983) as a screening. Volunteers whose trait anxiety scores were > or = 1 SD above (52.7 +/- 2.7, n = 9) or below (26.5 +/- 3.0, n = 11) the male college student normal values (38 +/- 9) participated in the study. Fat-free weight was assessed using a seven-site skinfold equation (A. S. Jackson and M. L. Pollock. Phys. Sports Med. 13: 76-90, 1985). Resting metabolism was measured (Sensormedics metabolic cart model 2900) at two separate trials (1-2 wk apart) in the early morning after a 12-h fast and 36 h postexercise. An analysis of covariance with fat-free weight as the covariate revealed a significantly greater (P < 0.005) RMR in the high trait anxious group than in the low trait anxious group. State anxiety (form Y-1) assessments made before and after each RMR measurement revealed a significant main effect of group such that state anxiety was higher in the high trait anxious than in the low trait anxious group for both trials before and after RMR measurement. Moreover, a significant (P < 0.003) main effect for the time factor was found showing that state anxiety was reduced after the RMR procedure. The results of this study show that a statistically significant portion of the variance in RMR can be accounted for by individual differences in anxiety.