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We present quantitative pulse-shaping-based two-photon fluorescence resonance energy transfer microscopy. We tailor the spectral phase of the excitation pulses to achieve selective excitation of donor and acceptor, demonstrating the method in live cells.

The nondelegation doctrine prohibits a legislature from delegating its power to an administrative agency, yet it is famously underenforced—even when the delegation results in the creation of criminal offenses (so-called “administrative crimes”). While this practice appears to scandalize the hornbook presumption that legislatures alone define criminal offenses, it has long been ratified by the Supreme Court and has received little scholarly attention. The few commentators who have addressed administrative crimes highlight the intuition that criminal sanctions are uniquely severe and thus deserving of a more rigorous nondelegation analysis, but they stop there. They do not precisely link the severe aspects of criminal punishment with a requirement for the type of institutions that can create criminal law. This Article provides that link. I argue that the two most significant dimensions of criminal punishment—community condemnation and liberty deprivation—implicate the concerns of two prominent political theories of punishment: expressivism and liberalism. A latent but mostly unstated premise of both theories, I claim, is that criminalization must be undertaken by a democratic institution. Given this, administrative crimes should be seen as illegitimate under either conception of state punishment.

The development of nosocomial ventilator-associated pneumonia (VAP) has been linked to the presence of specific bacteria found in the biofilm that develops in intubated endotracheal tubes of critical care patients. Presence of biofilm has been difficult to assess clinically. Here, we use Optical coherence tomography (OCT), to visualize the biofilm at both the proximal and distal tips. Ultimately, the goal will be to determine if OCT can be a tool to visualize biofilm development and potential interventions to reduce the incidence of VAP.

Humans now play a major role in altering Earth and its biota. Finding ways to ameliorate human impacts on biodiversity and to sustain and restore the ecosystem services on which we depend is a grand scientific and societal challenge. Conservation paleobiology is an emerging discipline that uses geohistorical data to meet these challenges by developing and testing models of how biota respond to environmental stressors. Here we (a) describe how the discipline has already provided insights about biotic responses to key environmental stressors, (b) outline research aimed at disentangling the effects of multiple stressors, (c) provide examples of deliverables for managers and policy makers, and (d) identify methodological advances in geohistorical analysis that will foster the next major breakthroughs in conservation outcomes. We highlight cases for which exclusive reliance on observations of living biota may lead researchers to erroneous conclusions about the nature and magnitude of biotic change, vulnerability, and resilience.

Our theoretical findings on instability of Faraday waves at megahertz (MHz) drive frequency and realization of silicon-based MHz multiple-Fourier horn ultrasonic nozzles (MFHUNs) together have enabled generation of mono-disperse droplets of controllable diameter (2.5-6.0 μm) at very low electrical drive power (

A versatile silicon-based ultrasonic nebulizer that utilizes a twin-nozzle of multiple Fourier horns at 1-2 MHz drive frequencies has been realized to perform simultaneous aerosolization of cobinamide and magnesium thiosulfate drug solutions. The drive frequency of the individual nozzle for a desirable aerosol diameter was individually designed. Using the 2.0 MHz 4-Fourier horn twin-nozzle aerosols of the two drug solutions with mass median diameter (MMD) of 3.0±0.1μm and geometrical standard deviation (GSD) of 1.18±0.02 and total flow rate up to 400μL/min were produced.

Background and purposeHydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity.MethodsNew Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2--IV hydroxocobalamin (N = 7); Group 3--IV aquohydroxocobinamide (N = 6); Group 4--IV sulfitocobinamide (N = 6); Group 5--intramuscular (IM) sulfitocobinamide (N = 6); and Group 6-IM dinitrocobinamide (N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS).ResultsCompared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control.ConclusionsCobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration.

A versatile silicon-based ultrasonic nebulizer that utilizes a twin-nozzle of multiple Fourier horns at 1-2 MHz drive frequencies has been realized to perform simultaneous aerosolization of cobinamide and magnesium thiosulfate drug solutions. The drive frequency of the individual nozzle for a desirable aerosol diameter was individually designed. Using the 2.0 MHz 4-Fourier horn twin-nozzle aerosols of the two drug solutions with mass median diameter (MMD) of 3.0±0.1μm and geometrical standard deviation (GSD) of 1.18±0.02 and total flow rate up to 400μL/min were produced.

This Article presents evidence that police are writing laws that they enforce. This newly discovered phenomenon compounds the existing understanding of police "making" law through the exercise of discretion. They make law in a far more direct way, functioning as quasi-legislators at the local level--identifying a social problem, drafting an offense to address it, and directly proposing their offense for enactment. The conduct targeted, and the reasons for doing so, are diverse. For example, in one city a police chief successfully criminalized public intoxication so that intoxicated people would go to jails instead of hospitals; in another, a chief pushed through an anti-vaping ordinance because of news articles he read about the dangers of e-nicotine. Contextualizing police-made law within policing theory and local government structure makes it less surprising, but we should be critical of it in many cases. Democratic political theory sets requirements for when bureaucratic interest groups may legitimately influence legislative deliberation, and police often fail to meet these. Basic expectations of neutrality and expertise, derived from administrative law, are often lacking. Moreover, the power of police to use violence makes them more analogous to military officials than to administrative agencies. This should trigger a strong norm of civilian control and a presumption against advocacy in policymaking. Police-made law changes how we understand the role of police in governance. Rather than being the downstream recipients of extraneously conferred authority, they are active participants in the expansion of their own power. Police are not mere agents of the mass misdemeanor system--they are also its architects. [ABSTRACT FROM AUTHOR]

Silicon-based MHz ultrasonic multiple Fourier horns in resonance are capable of producing high-throughput micrometer-sized droplets at low drive power. The centimeter-sized nozzles together with low power requirement enabled most recent realization of the first pocket-sized ultrasonic nebulizer (8.6 × 5.6 × 1.5 cm3) that contains nozzle, IC electronic driver, cell-phone battery, micro pump, drug reservoir, and liquid feed. A variety of common drugs for asthma, chronic obstructive pulmonary disease (COPD), diabetics, cyanide poisoning, pulmonary fibrosis, etc. such as albuterol, Humulin U-100, cobinamide, interferon-γ, and budesonide suspension have been nebulized with desirable aerosol size and throughput. © 2013 IEEE.

Detoxification of massive cyanide (CN) poisoning by inhalation of antidotes is recognized to be superior to intra venous (IV) or intra muscular (IM) treatment with regard to ease of administration, self-administration, and rapidity of onset. However, there are currently no effective, portable, high-throughput inhalers that can be produced in large quantities and distributed for such purpose. A hand-held inhaler has been realized using silicon-based ultrasonic nozzle to produce high-throughput of monodisperse cobinamide antidote solution for detoxification of CN poisoning in a rabbit model. © 2012 IEEE.

For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy. We report our progress on the probe design and imaging system for achieving a miniature catheter that is capable for in vivo animal study. The integrated IVUS-OCT catheter is featured by a sequential arrangement of an ultrasound transducer and an OCT probe. The capability of the integrated IVUS-OCT imaging catheter and system is demonstrated by in vitro and in vivo imaging experiments of rabbit abdominal aorta. © 2012 IEEE.

A miniature integrated optical coherence tomography (OCT) - ultrasound (US) probing system for real-time intravascular imaging has been developed. The outer diameter of the integrated probe is 0.69 mm, which is small enough for imaging in human coronary arteries. This probe, which has high resolution and deep tissue penetration, is designed to identify vulnerable atherosclerotic plaques in coronary arteries. The first in vivo images of a rabbit abdominal aorta obtained by the integrated OCT-US probe are presented. © 2012 SPIE.

A miniature integrated intravascular optical coherence tomography (OCT) - ultrasound (US) catheter for real-time imaging of atherosclerotic plaques has been developed, providing high resolution and deep tissue penetration at the same time. This catheter, with an outer diameter of 1.18mm, is suitable for imaging in human coronary arteries. The first in vivo 3D imaging of atherosclerotic microstructure in a rabbit abdominal aorta obtained by an integrated OCT-US catheter is presented. In addition, in vitro imaging of cadaver coronary arteries were conducted to demonstrate the imaging capabilities of this integrated catheter to classify different atherosclerotic plaque types.

ObjectiveTo characterize Alexander disease (AxD) phenotypes and determine correlations with age at onset (AAO) and genetic mutation. AxD is an astrogliopathy usually characterized on MRI by leukodystrophy and caused by glial fibrillary acidic protein (GFAP) mutations.MethodsWe present 30 new cases of AxD and reviewed 185 previously reported cases. We conducted Wilcoxon rank sum tests to identify variables scaling with AAO, survival analysis to identify predictors of mortality, and χ(2) tests to assess the effects of common GFAP mutations. Finally, we performed latent class analysis (LCA) to statistically define AxD subtypes.ResultsLCA identified 2 classes of AxD. Type I is characterized by early onset, seizures, macrocephaly, motor delay, encephalopathy, failure to thrive, paroxysmal deterioration, and typical MRI features. Type II is characterized by later onset, autonomic dysfunction, ocular movement abnormalities, bulbar symptoms, and atypical MRI features. Survival analysis predicted a nearly 2-fold increase in mortality among patients with type I AxD relative to those with type II. R79 and R239 GFAP mutations were most common (16.6% and 20.3% of all cases, respectively). These common mutations predicted distinct clinical outcomes, with R239 predicting the most aggressive course.ConclusionsAAO and the GFAP mutation site are important clinical predictors in AxD, with clear correlations to defined patterns of phenotypic expression. We propose revised AxD subtypes, type I and type II, based on analysis of statistically defined patient groups.

We report on the development of a multimodal optical coherence tomography (OCT) - ultrasound (US) system and miniaturized OCT-US probe for intravascular imaging. Both OCT optical components and a US transducer were integrated into a single probe, enabling both OCT and US imaging at the same time. A miniaturized OCT-US probe using a single element transducer was designed with a maximum outer diameter of 0.8 mm, which is suitable for in vivo intravascular imaging. The integrated OCT-US imaging system adopted a two-channel data acquisition card to digitize both OCT and US signals. Simultaneous OCT and US data processing and image display were also achieved using our home-developed software. In vitro OCT and US imaging of human aortic tissue was performed using this multimodal imaging system, which demonstrated the feasibility of the OCT-US system in intravascular imaging and its potential in detection of atherosclerotic plaques. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

In this study, we hypothesized that non-invasive continuous wave near-infrared spectroscopy (CWNIRS) can determine the severity or reversibility of muscle damage due to ischemia/reperfusion (I/R), and the results will be highly correlated with those from physical examination and histological analysis. To test this hypothesis, we performed CWNIRS measurements on two groups of male Sprague-Dawley rats ( approximately 400 g) that underwent 2 h (n = 6) or 3 h (n = 7) of pneumatic tourniquet application (TKA). Tissue oxyhemoglobin [HbO(2)] and deoxyhemoglobin [Hb] concentration changes were monitored during the 2 h or 3 h of 250 mmHg TKA and for an additional 2 h post-TKA. Rats were euthanized 24 h post-TKA and examined for injury, edema and viability of muscles. Contralateral muscles served as controls for each animal. In both groups, [HbO(2)] dropped immediately, then gradually decreased further after TKA and then recovered once the tourniquet was released. However, releasing after 2 h of TKA caused [HbO(2)] to overshoot above the baseline during reperfusion while the 3 h group continued to have lower [HbO(2)] than baseline. We found a significant correlation between the elapsed time from tourniquet release to the first recovery peak of [HbO(2)] and the muscle weight ratio between tourniquet and contralateral limb muscles (R = 0.86). Hemodynamic patterns from non-invasive CWNIRS demonstrated significant differences between 2 h and 3 h I/R. The results demonstrate that CWNIRS may be useful as a non-invasive prognostic tool for conditions involving vascular compromise such as extremity compartment syndrome.

We present a three-dimensional (3-D) endoscopic optical coherence tomography (OCT) system using a dual axis scanning mirror. The MEMS device employed in this study utilized a 1.2 mm mirror and exhibited x and y-axis resonant frequencies greater than 1 kHz. The developed probe was packaged and integrated with an OCT system which has a scan rate of 3∼8 frames/s. Preliminary in vivo and in vitro 3-D OCT images of biological tissue, such as human finger, vocal cord, rabbit trachea, were visualized to verify the achieved performance of the device.

Serial blood draws for the assessment of trauma patients' hemoglobin (sHgb) and hematocrit (sHct) is standard practice. A device that would allow for continuous real-time, non-invasive monitoring of hemoglobin and tissue perfusion would potentially improve recognition, monitoring and resuscitation of blood loss. We developed a device utilizing diffuse optical spectroscopy (DOS) technology that simultaneously measures tissue scattering and near-infrared (NIR) absorption to obtain non-invasive measurements of oxy- (Hb-O(2)), deoxyhemoglobin (Hb-R) concentrations and tissue hemoglobin concentration (THC) in an animal model of hypovolemic shock induced by successive blood withdrawals. Intubated New Zealand White rabbits (N = 16) were hemorrhaged via a femoral arterial line every 20 min until a 20% blood loss (10-15 cc kg(-1)) was achieved to attain hypovolemia. A broadband DOS probe placed on the inner thigh was used to measure muscle concentrations of Hb-O(2) and Hb-R, during blood withdrawal. THC and tissue hemoglobin saturation (S(T)O(2)) were calculated from DOS [Hb-O(2)] and [Hb-R]. Broadband DOS-measured values were compared against traditional invasive measurements: systemic sHgb, arterial oxygen saturation (S(a)O(2)) and venous oxygen saturation (S(v)O(2)) drawn from arterial and central venous blood. DOS and traditional invasive measurements versus blood loss were closely correlated (r(2) = 0.96) showing a decline with removal of blood. S(T)O(2) and [Hb-O(2)] followed similar trends with hemorrhage, while [Hb-R] remained relatively constant. These measurements may be limited to some extent by the inability to distinguish between hemoglobin and myoglobin contributions to DOS signals in tissue at this time. Broadband DOS provides a potential platform for reliable non-invasive measurements of tissue oxygenated and deoxygenated hemoglobin and may accurately reflect the degree of systemic hypovolemia and compromised tissue perfusion.

Optical coherence tomography (OCT) is a new modality capable of cross sectional imaging of biological tissue. Due to its many technical advantages such as high image resolution, fast acquisition time, and noninvasive capabilities, OCT is potentially useful in various medical applications. Because OCT systems can function with a fiber optic probe, they are applicable to almost any anatomic structures accessible either directly, or by endoscopy. OCT has the potential to provide a fast and noninvasive means for early clinical detection, diagnosis, screening, and monitoring of precancer and cancer. With an imaging depth range of 2-3 mm, OCT diagnostics are particularly suitable for the oral mucosa. Currently, it is difficult to detect premalignant and malignant oral lesions due to their often multifocal nature and need for repeated biopsies. The goal of this study was to evaluate the feasibility of OCT for the diagnosis of multiple stages of oral cancer progression. In this paper, we present not only conventional 2-D OCT images, but also 3-D volume images of normal and precancerous lesions. Our results demonstrate that OCT is a potential tool for cancer detection with comprehensive diagnostic images. © 2005 IEEE.

BackgroundMethods for obtaining real-time in vivo histologic resolution by means of noninvasive endoscopic optical imaging would be a major advance for thoracic surgical diagnostics and treatment. Optical coherence tomography is a rapidly evolving technology based on near-infrared interferometry that might provide these capabilities. The purpose of this study is to investigate the feasibility of real-time 2- and 3-dimensional optical coherence tomographic imaging of airway, pleural, and subpleural lung tissues in normal, inflammatory, and malignant animal models and patients with known or suspected airway malignancy.MethodsFreshly excised lungs and pleural tissue obtained from rabbits with inhalation lung injury and induced empyema, metastatic sarcomas, and pleural sarcomas and from patients with airway disease were imaged by using 2- and 3-dimensional optical coherence tomography with a prototype superluminescent diode optical coherence tomographic system constructed in our laboratory. Lungs and pleural tissue were subsequently processed for standard hematoxylin and eosin histology for comparison with optical coherence tomography.ResultsOptical coherence tomographic imaging achieved an ex vivo resolution of 10 microm and an in vivo resolution of about 30 microm with a depth penetration of 1 to 2 mm with 2- and 3- dimensional reconstruction capabilities. Tumors as small as 500 microm were detectable with optical coherence tomography. The acquired images closely matched histologic images, demonstrating details at the level of mucosal layers, glands, alveoli, and respiratory bronchioles.ConclusionsOptical coherence tomography with near-infrared interferometric methods enables near real-time in vivo near-histologic resolution optical imaging. With further advances, optical coherence tomography has the potential for real-time accurate and early pleural and subpleural diagnostics by using small-diameter flexible fiberoptic endoscopic probes for a wide range of thoracic surgical applications.

We suggest that Optical coherence tomography (OCT) is a potential imaging modality capable of assisting diagnosis in pulmonary medicines. OCT can provide extremely high resolution imaging and be performed with flexible fiber-optic bronchoscopy with small diameter endoscopic probes. In this study, animal models of trachea, and lung surface were to investigate utility of OCT in pulmonary. Normal, malignant, and infectious disease animal model samples measured by OCT were compared to standard histologic H&E light microscopic imaging of the same sites.