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PubMed2004

Electromyographic activity and strength during maximum isometric pronation and supination efforts in healthy adults.

There exists a lack of quantitative data in the literature related to the torque produced during axial forearm rotation and the electromyographic (EMG) activity of the muscles involved. Therefore, the purpose of this study was to compare the relative EMG activity of four forearm muscles during resisted forearm rotation. A custom-built device capable of measuring torque in the absence of grip was employed. Fourteen healthy volunteers performed maximum isometric voluntary contractions in five positions of axial forearm rotation for both pronation and supination. EMG data were collected simultaneously from the supinator, biceps, pronator quadratus (deep and superficial heads), and pronator teres muscles using fine-wire bipolar electrodes. Data were analyzed to determine the contributions of each muscle to pronation and supination torque over five positions of forearm rotation. In the absence of grip no significant difference was found between supination and pronation torque in neutral position. Supination torque generation was greater in the pronated forearm positions, and pronation torque was greater in the supinated positions (p<0.05). A root-mean-square EMG analysis verified the major contributions of the pronator teres and both heads of the pronator quadratus muscle to pronation torque, and supinator and biceps to supination torque. The deep head of the pronator quadratus was active during both pronation and supination, lending support to the theory that it may act primarily as a dynamic distal radioulnar joint stabilizer. This information may be helpful in upper extremity modeling, surgical treatments, and rehabilitation strategies.

Adult↗

PubMed2006

High-performance, static-coated silicon microfabricated columns for gas chromatography.

A procedure is described for the preparation of high-performance etched silicon columns for gas chromatography. Rectangular channels, 150 mum wide by 240 mum deep are fabricated in silicon substrates by gas-phase reactive ion etching. A 0.1-0.2-mum-thick film of dimethyl polysiloxane stationary phase is deposited on the channel walls by filling the channel with a dilute solution in 1:1 n-pentane and dichloromethane and pumping away the solvent. A thermally activated cross-linking agent is used for in situ cross-linking. A 3-m-long microfabricated column generated approximately 12 500 theoretical plates at optimal operating conditions using air as carrier gas. A kinetic model for the efficiency of rectangular cross-section columns is used to evaluate column performance. Results indicate an additional source of gas-phase dispersion beyond longitudinal diffusion and nonequilibrium effects, probably resulting from numerous turns in the gas flow path through the channel. The columns are thermally stable to at least 180 degrees C using air carrier gas. Temperature programming is demonstrated for the boiling point range from n-C5 to n-C12. A 3.0-m-long column heated at 10 degrees C/min obtains a peak capacity of over 100 peaks with a resolution of 1.18 and a separation time of approximately 500 s. With a 0.25-m-long column heated at 30 degrees C/min, a peak capacity of 28 peaks is obtained with a separation time of 150 s. Applications are shown for the analysis of air-phase petroleum hydrocarbons and the high-speed analysis of chemical warfare agent and explosive markers.

Air Pollutants↗

PubMed2002

Cortical sources of the early components of the visual evoked potential.

This study aimed to characterize the neural generators of the early components of the visual evoked potential (VEP) to isoluminant checkerboard stimuli. Multichannel scalp recordings, retinotopic mapping and dipole modeling techniques were used to estimate the locations of the cortical sources giving rise to the early C1, P1, and N1 components. Dipole locations were matched to anatomical brain regions visualized in structural magnetic resonance imaging (MRI) and to functional MRI (fMRI) activations elicited by the same stimuli. These converging methods confirmed previous reports that the C1 component (onset latency 55 msec; peak latency 90-92 msec) was generated in the primary visual area (striate cortex; area 17). The early phase of the P1 component (onset latency 72-80 msec; peak latency 98-110 msec) was localized to sources in dorsal extrastriate cortex of the middle occipital gyrus, while the late phase of the P1 component (onset latency 110-120 msec; peak latency 136-146 msec) was localized to ventral extrastriate cortex of the fusiform gyrus. Among the N1 subcomponents, the posterior N150 could be accounted for by the same dipolar source as the early P1, while the anterior N155 was localized to a deep source in the parietal lobe. These findings clarify the anatomical origin of these VEP components, which have been studied extensively in relation to visual-perceptual processes.

Adolescent↗

PubMed2002

Risk reduction in pediatric procedural sedation by application of an American Academy of Pediatrics/American Society of Anesthesiologists process model.

OBJECTIVE: Guidelines for risk reduction during procedural sedation from the American Academy of Pediatrics (AAP) and the American Society of Anesthesiologists (ASA) rely on expert opinion and consensus. In this article, we tested the hypothesis that application of an AAP/ASA-structured model would reduce the risk of sedation-related adverse events. METHODS: Prospectively coded sedation records were abstracted by a hospital quality improvement specialist with practical and administrative experience in pediatric sedation. Process variables included notation of nulla per os (NPO) status, performance of a guided risk assessment, assignment of ASA physical status score, obtaining informed consent, generation of a sedation plan, and assessment of sedation level using a quantitative scoring system. Content variables included adherence to AAP NPO guidelines, ASA class, target sedation level, actual sedation level, age, procedure, and drugs used. Complication risk was assessed by logistic regression and Mantel-Haenszel odds ratios (OR). RESULTS: Complications were identified in 40 of 960 records (4.2%). The complication rate was 34 of 895 (3.8%) with planned conscious sedation and 6 of 65 (9.2%) with planned deep sedation ([DS]; OR: 2.6). Complications were reduced by performance of structured risk assessment (OR: 0.10), adherence to all process guidelines (OR: 0), and avoiding actual DS (OR: 0.4). The only drug associated with higher risk was chloral hydrate (OR: 2.1). Failure to adhere to NPO guidelines did not increase risk in this assessment; however, the adverse event rate was 0 if all process guidelines were followed. CONCLUSIONS: Presedation assessment reduces complications of DS. Repeated assessment of sedation score reduces the risk of inadvertent DS. The data provide direct evidence that AAP/ASA guidelines can reduce the risk of pediatric procedural sedation.

Anesthesia↗

PubMed2003

Selective hyperthermia using magnetoliposomes to target cervical lymph node metastasis in a rabbit tongue tumor model.

The effect of hyperthermia on cervical lymph node metastasis of VX7 tongue cancer in female Japanese white rabbits was investigated. Magnetoliposomes (MLs) with a neutral surface charge and a size of 94.1 nm were used as heating mediators. MLs were injected into the tongue 20 days after tumor transplantation, and we examined whether they reached the metastatic deep cervical lymph node. The highest magnetite concentration 24 h after ML injection was detected in the lymph node, followed by tongue, spleen, blood, and liver. Rabbits were separated into three groups: group I as the control; group II with ML injection alone; and group III with ML injection and hyperthermia 24 h after ML injection, generated by applying an alternating magnetic field (118 kHz, 384 Oe) to the neck region. The hyperthermic effect was evaluated in terms of the percentage of necrosis in proportion to the metastatic tumor and the apoptotic index (AI), defined as the ratio of TUNEL-positive cells. The temperature of lymph nodes in group III reached over 44 degrees C. The mean area of necrosis in group III was 58.0%, which was significantly higher than that in group I (19.6%) or group II (20.4%). The AI in group III was 22.9%, significantly higher than in group I (1.67%) or II (1.42%). The difference between group I and II was not statistically significant. Group III tumor sites around MLs showed necrosis or apoptosis-positive cells induced by hyperthermia. These results indicate that MLs injected into the tongue can target cervical lymph node metastases and accumulate there at concentrations sufficient to generate therapeutically effective temperatures.

Animals↗

PubMed2001

Glycolipid targets of CD1-mediated T-cell responses.

Members of the CD1 family of antigen-presenting molecules bind and present a variety of mammalian and microbial glycolipids for specific recognition by T cells. CD1 proteins accomplish their antigen-presenting function by binding the alkyl chains of the antigens within a deep, hydrophobic groove on the membrane distal surface of CD1, making the hydrophilic elements of the antigen available for contact with the variable regions of antigen-specific T-cell receptors. Most models of CD1-restricted T cells function in infectious, neoplastic, or autoimmune diseases and are based on the premise that CD1-restricted T-cell responses are initiated by alterations in cellular glycolipid content. Although a growing number of self, altered self and foreign glycolipid antigens have been identified, the cellular mechanisms that could lead to the generation of antigenic glycolipids within cells, or control the presentation of particular classes of altered self or microbial glycolipids in disease states have only recently come under investigation. Here we review the structures of known glycolipid antigens for T cells and discuss how the chemical nature of these antigens, which is quite different from that of peptides, influences their recognition by T cells.

Animals↗

PubMed1997

Rupture of lens cataract: a novel hereditary recessive cataract model in the mouse.

The RLC is a new mouse model of hereditary cataract. In this mutant, opacity of lens developed spontaneously at 35-60 days of age. The initial histological change was irregular swelling, condensation, degeneration and fragmentation of lens fibers in the deep cortex, leading to rupture of the lens capsule at the posterior pole at 45-100 days of age. Following rupture, the lens nucleus dislocated behind the lens or occasionally in the anterior chamber. Both eyes were affected. Genetic analysis indicated that the mutation was dictated by a single autosomal recessive gene with complete penetrance. Homozygotes of either sex developed cataract with rupture of lens capsule. We named the responsible gene as rupture of lens cataract (rlc) and the mouse strain as RLC. Neither allelism nor linkage was found between rlc and nct, another recessive gene in Nakano cataract mice. The rlc mutation is now fixed in a inbred background since the RLC has been maintained over 20 inbred generations in the laboratory. Although no direct homologous disease of this unusual cataract is found in human, this mutant will provide a valuable tool to investigate the mechanism involved in maintainance of lens.

Animals↗

PubMed1994

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Adult↗

PubMed2004

Complete mitochondrial genome DNA sequence for two ophiuroids and a holothuroid: the utility of protein gene sequence and gene maps in the analyses of deep deuterostome phylogeny.

The complete mitochondrial genome sequences have been determined for the holothuroid Cucumaria miniata and two ophiuroid species Ophiopholis aculeata and Ophiura lütkeni. In addition, the nucleotide sequence of the mitochondrial protein-coding genes for the asteroid Pisaster ochraceus has been completed. Maximum-likelihood and LogDet distance analyses of concatenated protein-coding sequences produced a series of trees that did not conclusively support generally accepted models of echinoderm phylogeny. The ophiuroid data consistently demonstrated accelerated nucleotide divergence rates and lack of stationarity. This confounds the phylogenetic analyses. Molecular investigations using individual protein-coding gene alignments demonstrated that the cytochrome b gene exhibits the least deviation in rate and stationarity and generated some trees consistent with proposed echinoderm phylogenies. Phylogenies based on echinoderm mitochondrial gene rearrangements also proved problematic because of extensive variation in gene order between and within classes. A comparison of the two distinctive ophiuroid mitochondrial gene orders supports the hypothesis that O. lütkeni has a more derived mitochondrial gene order versus O. aculeata. The variation in the echinoderm mitochondrial gene maps reinforces the limitations of the application of mitochondrial gene rearrangements as a global phylogenetic tool.

Animals↗

PubMed2000

Numerical simulation of ultrasound-thermotherapy combining nonlinear wave propagation with broadband soft-tissue absorption.

Ultrasound (US) thermotherapy is used to treat tumours, located deep in human tissue, by heat. It features by the application of high intensity focused ultrasound (HIFU), high local temperatures of about 90 degrees C and short treating time of a few seconds. Dosage of the therapy remains a problem. To get it under control, one has to know the heat source, i.e. the amount of absorbed US power, which shows nonlinear influences. Therefore, accurate simulations are essential. In this paper, an improved simulation model is introduced which enables accurate investigations of US thermotherapy. It combines nonlinear US propagation effects, which lead to generation of higher harmonics, with a broadband frequency-power law absorption typical for soft tissue. Only the combination of both provides a reliable calculation of the generated heat. Simulations show the influence of nonlinearities and broadband damping for different source signals on the absorbed US power density distribution.

Computer Simulation↗

PubMed2001

Phylogenetic and familial estimates of mitochondrial substitution rates: study of control region mutations in deep-rooting pedigrees.

We studied mutations in the mtDNA control region (CR) using deep-rooting French-Canadian pedigrees. In 508 maternal transmissions, we observed four substitutions (0.0079 per generation per 673 bp, 95% CI 0.0023-0.186). Combined with other familial studies, our results add up to 18 substitutions in 1,729 transmissions (0.0104), confirming earlier findings of much greater mutation rates in families than those based on phylogenetic comparisons. Only 12 of these mutations occurred at independent sites, whereas three positions mutated twice each, suggesting that pedigree studies preferentially reveal a fraction of highly mutable sites. Fitting the data through use of a nonuniform rate model predicts the presence of 40 (95% CI 27-54) such fast sites in the whole CR, characterized by the mutation rate of 274 per site per million generations (95% CI 138-410). The corresponding values for hypervariable regions I (HVI; 1,729 transmissions) and II (HVII; 1,956 transmissions), are 19 and 22 fast sites, with rates of 224 and 274, respectively. Because of the high probability of recurrent mutations, such sites are expected to be of no or little informativity for the evaluation of mutational distances at the phylogenetic time scale. The analysis of substitution density in the alignment of 973 HVI and 650 HVII unrelated European sequences reveals that the bulk of the sites mutate at relatively moderate and slow rates. Assuming a star-like phylogeny and an average time depth of 250 generations, we estimate the rates for HVI and HVII at 23 and 24 for the moderate sites and 1.3 and 1.0 for the slow sites. The fast, moderate, and slow sites, at the ratio of 1:2:13, respectively, describe the mutation-rate heterogeneity in the CR. Our results reconcile the controversial rate estimates in the phylogenetic and familial studies; the fast sites prevail in the latter, whereas the slow and moderate sites dominate the phylogenetic-rate estimations.

Canada↗

PubMed1983

Capillary transport of H2 gas generated locally in renal tissue.

Previous measurements by microspheres have shown a higher blood flow in outer cortex and a lower blood flow in inner cortex than found by diffusible tracers. During vasodilation microspheres have indicated a disproportionate increase in deep cortical blood flow, whereas diffusible tracer distributions remained unchanged. These discrepancies could possibly be explained by a variable net inward transport of diffusible tracers in postglomerular vessels, the transport existing in control, but disappearing during vasodilation. To test this hypothesis H2 gas was produced electrolytically for 1 s at a platinum electrode in midcortex and the resulting gas concentration curve measured polarographically at two electrodes placed above and below the source. Analysis of a mathematical model showed that the ratio of the curve maxima at the two electrodes (Cmo/Cmi) would best reveal a radial net transport. Average Cmo/Cmi at 25 positions in 7 clamped dog kidneys was close to unity, but rose to 1.24 at control flow. During acetylcholine infusion Cmo/Cmi rose to 1.68. Local washout rates at the two electrodes increased equally. Calculations indicated a small outwardly directed net transport in control (3 X 10(-4) cm/s), becoming slightly reinforced during vasodilation (5 X 10(-4) cm/s). Thus the control transport direction is opposite to the hypothesis, and the change during vasodilation was estimated to be too small to explain the disparity between diffusible tracer uptake and microsphere distribution in control. H2 concentration maximum was obtained earlier under control flow than in the clamped kidney, indicating an increase in apparent D of the gas in tissue from 3 X 10(-5) cm2/s to 5 X 10(-5) cm2/s, probably due to mixing of H2 gas in the capillary net work.

Acetylcholine↗

PubMed1997

Possibilities and limitations of magnetic source imaging of methohexital-induced epileptiform patterns in temporal lobe epilepsy patients.

The usefulness of MEG-based techniques in lateralizing and localizing the epileptogenic area was investigated in the present study. Spontaneous and methohexital-induced spikes were studied in a group of 15 patients with temporomesial epilepsy using a 37-channel neuromagnetometer. The accuracy of the magnetic source imaging was compared to the results of electrocorticographic (ECoG) recordings. Differences of drug-induced spike densities in the MEG recordings between both sides confirmed a similar lateralizing power of the MEG and ECoG recordings. Source location analyses based on a moving dipole model resp. a rotating dipole model were performed using a spherical head model. After subdivision of the volume of each patient's head, 8 cm3 cubicles containing at least 3 source locations were projected onto the individual MRI scan and resulted in source locations within or close to the presurgically defined primary epileptogenic area only in 3 of the 15 patients. Spike induction by methohexital has the advantage of shortening the recording period as compared to recordings of interictal epileptiform discharges. However, the correlation analyses of spike densities from MEG and ECoG recordings and the source location analyses from MEG recordings indicate that spike generated in deep temporomesial structures may escape the MEG registration.

Adolescent↗

PubMedDate not supplied

Thermal stress study of two different artery cryopreservation methods.

Two methods used in artery deep cryopreservation, "Cryopreservation in Medium" and "Cryopreservation in Air", were studied. For the former method, samples were frozen together with a certain amount of cryoprotectants (CPA) in the cryovial or cryobag, while for the other method the arteries were first exposed to CPA and then frozen without the CPA medium surrounding in the cryovial. Study of the cryopreserved arteries using these two methods found that "cryopreservation in air" could substantially reduce the fracture rate of the arteries. To explain the difference theoretically, a two-compartment model is presented to study the thermal stresses generated during the freezing and thawing processes. The properties were measured as inputs to the model. Numerical results showed that the thermal stresses occurring in the "cryopreservation in air" process were much smaller than in the other method. The maximum thermal stress during cryopreservation occurs in the thawing process. The theoretical results could well explain published experimental results.

Air↗

PubMed2006

Reduced mixing generates oscillations and chaos in the oceanic deep chlorophyll maximum.

Deep chlorophyll maxima (DCMs) are widespread in large parts of the world's oceans. These deep layers of high chlorophyll concentration reflect a compromise of phytoplankton growth exposed to two opposing resource gradients: light supplied from above and nutrients supplied from below. It is often argued that DCMs are stable features. Here we show, however, that reduced vertical mixing can generate oscillations and chaos in phytoplankton biomass and species composition of DCMs. These fluctuations are caused by a difference in the timescales of two processes: (1) rapid export of sinking plankton, withdrawing nutrients from the euphotic zone and (2) a slow upward flux of nutrients fuelling new phytoplankton production. Climate models predict that global warming will reduce vertical mixing in the oceans. Our model indicates that reduced mixing will generate more variability in DCMs, thereby enhancing variability in oceanic primary production and in carbon export into the ocean interior.

Biomass↗

PubMed1998

Measurement of serosal temperatures and depth of thermal injury generated by thermal balloon endometrial ablation in ex vivo and in vivo models.

OBJECTIVE: To evaluate the safety profile of endometrial ablation performed with a thermal balloon as defined by serosal temperature elevation and depth of injury. DESIGN: Observational study with histopathologic correlation conducted in ex vivo and in vivo phases. SETTING: Academic medical center. PATIENT(S): Twenty patients undergoing total abdominal hysterectomy. INTERVENTION(S): Endometrial ablation with a thermal balloon. MAIN OUTCOME MEASURE(S): Serosal temperature elevation and histologic depth of injury. RESULT(S): Ex vivo phase results revealed serosal temperatures remained within a safe physiologic range (<45 degrees C). Greatest depth of myometrial injury in the premenopausal uteri was 5.8 mm over the anterior lower uterine segment. In postmenopausal uterus. the greatest depth of myometrial injury was 3.8 mm in the anterior midline. In vivo phase results revealed mean (+/- SD) peak serosal temperatures of 36.1 +/- 1.6 degrees C. As with the ex vivo phase. histologic examination revealed deep endometrial and superficial myometrial damage to all areas. The greatest depth of myometrial injury occurred in the midfundus at 3.4 mm. CONCLUSION(S): No patients experienced complications or adverse events secondary to treatment. Results showed that transuterine thermal injury is a highly unlikely scenario. In both phases of this study, histologic examination revealed that temperatures exposed to the endometrial layer were sufficient to cause tissue damage.

Adult↗

PubMed2025

Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pretrained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Selection, Genetic↗

PubMed2005

Gamma scintigraphic evaluation of a miniaturized AERx pulmonary delivery system for aerosol delivery to anesthetized animals using a positive pressure ventilation system.

The purpose of this study was to characterize performance of a miniaturized AERx((R)) Pulmonary Delivery System designed for aerosol administration to large animal models. The miniaturized AERx System was developed through a systematic scaling down of the AERx System used for humans to allow for operation in certain animal models with lower inspiratory flow rates and inhaled volumes than those used for humans. We used gamma scintigraphy to characterize the in vivo particle deposition achieved with the miniaturized AERx System in two dogs. The dogs were 3-4 years old, and weighed 10.4 kg and 13.6 kg. Acepromazine was used as pre-anesthetic medication. Anesthesia was induced with 5% isoflurane. The trachea was intubated using an endotracheal tube (internal diameter 8.5 mm), and the dogs were ventilated using positive pressure during the exposure using the LRRI puff generator. An inhalation of aerosol was initiated by activation of the puff generator though the computer-controlled interface. Each dog inhaled approximately 0.8 L per puff, of which the aerosol volume comprised approximately 0.25 L, at a target flow rate of 15 L/min. The dogs were exposed to 10 AERx Strips in 10 puffs. The mass median aerodynamic diameter of the aerosolized formulation was approximately 1.25 microm with a fine particle fraction <3.5 microm of 0.976. The scintigraphic images showed uniform bilateral lung deposition following aerosol delivery with the AERx System. Total lung deposition for the two dogs was 10.7% and 18% of the loaded dose from the AERx Strip. The corresponding peripheral lung: inner lung (P/I) ratios were 0.83 and 0.75, suggestive of deposition in the deep lung. Only 0.1% to 0.2% of the loaded dose was exhaled. These results show the miniature AERx System can efficiently deliver aerosols to the deep lung of dogs. The miniaturized AERx System would be a valuable tool for conducting proof-of-concept studies as well as safety and tolerability analysis of inhaled drug candidates in large animal models.

Administration, Inhalation↗