Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nanocell logic gates for molecular computing

Molecular electronics seeks to build electrical devices to implement computation - logic and memory - using individual or small collections of molecules. These devices have the potential to reduce device size and fabrication costs, by several orders of magnitude, relative to conventional CMOS. However, the construction of a practical molecular computer will require the molecular switches and their related interconnect technologies to behave as large-scale diverse logic, with input/output wires scaled to molecular dimensions. It is unclear whether it is necessary or even. possible to control the precise regular placement and interconnection of these diminutive molecular systems. This paper describes genetic algorithm-based simulations of molecular device structures in a nanocell where placement and connectivity of the internal molecular switches are not specifically directed and the internal topology is generally disordered. With some simplifying assumptions, these results show that it is possible to use easily fabricated nanocells as logic devices by setting the internal molecular switch states after the topological molecular assembly is complete. Simulated logic devices include an inverter, a NAND gate, an XOR gate and a 1-bit adder. Issues of defect and fault tolerance are addressed.     

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.     

Remote sensing of species mixtures in conifer plantations using LiDAR height and intensity data

In even-aged, single species conifer plantations LiDAR height data can be modelled to provide accurate estimates of tree height and volume. However, it is apparent that growth models developed for single species stands are not directly transferable to a more general situation of mixed species plantations. This paper evaluates the ability of small footprint, dual-return, pulsed airborne LiDAR data to estimate the proportion of the productive species when mixed with a nurse crop in closed canopy plantations. A study area located in Galloway Forest District in Scotland is used as an example of Lodgepole pine and Sitka spruce mixed plantation; this area contains good examples of a wide range of pure and mixed species plantation types. Three species groups are studied: areas of pure Sitka spruce, areas of pure Lodgepole pine and areas where the two species have been planted together. Two approaches are assessed for detection of plantation mixtures: the first uses LiDAR intensity data to separate spruce and pine species and the second uses LiDAR-derived canopy density measures, coefficient of variation, skewness, percent of ground returns (which provides a measure of canopy openness) and the mean canopy height, which enables areas with height variations to be identified. From analysis of LiDAR data extracted from 54 study plots using logistic regression, the coefficient of variation and LiDAR intensity data provide the most useful predictors of the proportion of spruce in a pine/spruce mixture with coefficients of determination (R²) of 0.914 and 0.930 respectively. The method could be developed as a mapping tool, which in combination with existing inventory data should help to improve timber volume forecasting for mixed species even-aged plantations.     

Optimization of gas-sensitive polymer arrays using combinations of heterogeneous and homogeneous subarrays

Results for optimizing an array of conducting polymer gas sensors for sensing one of five analytes in the presence of up to four interferents are presented. The optimized array consists of subarrays of homogeneous (like) sensors contributing to a larger heterogeneous array of up to ten points (unlike sensors) in multidimensional sensor space. The optimization techniques presented here are linear, since the polymer sensors in their useful (low concentration) operating range exhibit linear and additive response characteristics. The optimization of these arrays produces maximum separability between analytes, demonstrating the trade-off between the addition of both information and variability induced by increasing the size of the heterogeneous array. Optimization results for sensing acetone, hexane, THF, toluene, and ethanol in the presence of interferents result in array sizes that are significantly less than the maximum available number of sensors (ten in the heterogeneous partition of the array). This result adds fuel to the argument that fewer sensors are better; the argument for more sensors, however, is also made in the context of the electronic nose systems where significant chemical diversity is required. Homogeneous subarrays of up to four elements each improve the separability of analytes in these optimized heterogeneous arrays by over 10% and also effectively flag broken or unhealthy sensors in a manner that is independent of analyte and concentration.     

Sensor technologies for monitoring metabolic activity in single cells-part I: optical methods

A review of optical, chemical, and biological sensors to detect metabolic activity at the single-cell level is presented in the context of the development of lab-on-a-chip research instrumentation. The sensors reviewed include optical sensors, at both research and commercial levels, that can optically detect intracellular metabolites including adenosine triphosphate, nicotinamide-adenine dinucleotide, reduced flavin adenine dinucleotide, and other metabolites, including oxygen, carbon dioxide, and glucose. Methods to optically detect pH changes which are a general indicator of activity in extracellular space are also briefly reviewed. Performance metrics such as sensitivity, sensor size, drift, time response, and sensing range are included when available. Highly suitable optical sensor technologies for monitoring cellular metabolic activity include luminescent (fluorescent, phosphorescent, and chemiluminescent) and colorimetric optical probes. Different approaches to extracting luminescent and colorimetric information are reviewed, including benchtop techniques, fiber-optic approaches, and the use of probes encapsulated by biologically localized embedding. A brief discussion of alternate optical sensor technologies, such as surface plasmon resonance and infrared absorption spectroscopy, is also presented.     

Ophthalmologic findings in Usher syndrome type 2A

Thirty-seven patients, comprising 24 familial cases and 13 isolated patients with Usher syndrome type II (USH2), underwent ophthalmologic examination. Based on the degree of hearing loss, normal vestibular function, and gene-linkage analysis, familial cases were assumed to have USH2A. An analysis of genetic heterogeneity failed to reveal the presence of a second locus in the Dutch population. Although the patients appear to belong to a genetically homogeneous group, remarkable ophthalmologic variability was found. Corrected visual acuity decreased with age and remarkable differences in visual acuity were found within one family. Fundoscopic findings were classified as type A if attenuated vessels and bone corpuscles in all quadrants were found or as type B if findings other than these were found. The prevalence of type A significantly increased with age.     

The effect of a split in WAIS-R VIQ and PIQ scores on patients with cognitive impairment and psychiatric illness

To determine the most effective treatment for acrodermatitis chronica atrophicans, several clinical trials were undertaken in recent years to evaluate whether a 2-week course of ceftriaxone would be superior to oral antibiotics. Of the 46 patients suffering from acrodermatitis chronica atrophicans, 14 were treated with ceftriaxone 2g for 15 days. The remaining patients received either oral penicillin V 1.5 million IU t.i.d. or doxycycline 100 mg b.i.d. for 20 to 30 days. Patients were followed up for at least 1 year. Of the 14 ceftriaxone-treated patients four showed incomplete regression of the inflammatory skin changes after 6 to 12 months. Two out of five patients who were monitored for Borrelia burgdorferi DNA excretion were still positive after 12 months as compared to none of six patients who were treated orally for 20-30 days. Six out of 11 patients treated orally for only 20 days needed retreatment after 6 months because of continuing skin manifestations, neuropathy or arthralgia. A 30-day duration of treatment with oral antibiotics and not the chosen antibiotic is crucial for curing acrodermatitis chronica atrophicans. The duration of treatment with ceftriaxone needed for eradication of Borrelia in acrodermatitis chronica atrophicans has yet to be determined in future studies.