The optic nerve head, lamina cribrosa, and nerve fiber layer in non-myopic and myopic children.

The purpose of this study was to evaluate the optic nerve head, lamina cribrosa, retina, and choroid in school age children using spectral domain optical coherence tomography (SD-OCT) and to assess these structural parameters in relation to age, axial length, and refractive error. Healthy children, ages 11.15 ± 2.62 years (range 6-15 years, n = 53), underwent cycloplegic autorefraction, biometry, and SD-OCT imaging in both eyes. Images were analyzed using custom written programs in MATLAB, after adjustment for lateral magnification. Peripapillary retinal nerve fiber layer (RNFL) thickness, retinal and choroidal thicknesses, Bruch's membrane opening (BMO) area, minimum rim width (MRW), and anterior lamina cribrosa surface depth (ALCSD) were determined and analyzed with age, axial length, and refraction. Results show that axial length increased and refractive error became more myopic with increasing age (R2 = 0.25, ß = 0.18, P < 0.0001 and R2 = 0.27, ß = -0.37, P < 0.0001, respectively). Minimum foveal thickness and central 1 mm retinal thickness increased with increasing age (R2 = 0.15, ß = 2.38, P < 0.01 and R2 = 0.11, ß = 3.16, P < 0.05, respectively). Age-adjusted raw values for peripapillary RNFL thickness decreased with increasing axial length (R2 = 0.11, ß = -3.18, P < 0.05); however, this relationship was not present when image magnification was corrected (R2 = 0.07, ß = 2.72, P = 0.09). BMO area increased with myopic refractive error (R2 = 0.16, ß = -0.10, P < 0.01). Age-adjusted vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error (R2 = 0.12, ß = -0.05, P < 0.05 and R2 = 0.11, ß = 0.03, P = 0.05, respectively). Mean MRW, mean ALCSD, and peripapillary choroidal thickness were not associated with age, axial length, or refraction. Mean MRW was significantly thinner in eyes with deeper ALCS (R2 = 0.41, ß = -0.83, P < 0.0001). These findings provide normal values for retinal and optic nerve head parameters in school age children, and also suggest that ocular remodeling occurs in some structures in school age children with normal eye growth and during early stages of myopia development.

Comparison of intraoral and extraoral scanners on the accuracy of digital model articulation.

Digital dental technology is increasingly becoming an integral part of the modern orthodontic practice. The accuracy of digitally articulated models is critical when developing orthodontic treatment plans. OBJECTIVE: to determine the accuracy of model articulation generated by extraoral and intraoral scanners. DESIGN: One extraoral scanner with a wax (EOW) or vinyl polysiloxane bite registration (EOVPS), and three intraoral digital scanners utilizing confocal static (IOCS), confocal continuous (IOCC), and blue LED light technologies (IOLED) were used. METHODS: On each scanned image (n = 25 per group), measurements between the maxillary and mandibular molars and canines were performed and then compared to the gold standard values. A deviation of ± 0.5 mm from the gold standard value was considered acceptable. The significance level was kept at 0.05. RESULTS: IOCS and IOCC were accurate for all six interarch measurements. IOLED and EOVPS groups produced the next most accurate articulation of the digital models. EOW group resulted in the least accurate articulation. Also, of the software platforms used, the OrthoCAD™ was found to be the most accurate system for making measurements on digital casts. CONCLUSIONS: Only the scanners with the confocal imaging technology produced accurately articulated models. Differences between the scanners may be related to measurement errors inherent to the technologies employed and the software systems used to process the images.

Accounting Basics Part 3: Time Value and Internal Rate of Return.

Understanding the principles behind the time value of money can help individuals succeed in both business and personal long-term planning. The Internal Rate of Return (IRR) method provides a straightforward way to analyze long-term financial decisions. The result, the project's IRR, is a simple percentage that is easy to explain and compare with the results from other projects. When considering multiple investments, it is relatively simple to rank them by their IRRs, make minor adjustments to the list for qualitative issues, and invest down the list until the funds for the year have been spent.

Accounting Basics Part 4: Net Present Value.

MaKing and justitying capital expenditures can be a difficult part of a supervi- sory or managerial position. Understanding more advanced accounting tools for justifying these expenditures, like Internal Rate of Return (IRR) and Net Present Value (NPV), can improve the chances of receiving necessary funding. NPV avoids the weaknesses of the IRR method by allowing decision makers to specify when cash flows will occur instead of assuming that net cash flows will be equal each year ofa project. Taking the time to learn basic account- ing definitions and tools can improve your ability to manage and provide greater opportunities to help patients, staff, and the community.

Accounting Basics, Part 2: Justify Capital Spending.

Making and justifying capital expenditures can be a difficult part of a supervisory or managerial position. Understanding some basic tools for making estimates and calculating values can help simplify this process. Breaking down some of the most common accounting methods into a six-step, intuitive process allows everyone, even those with little or no accounting background, to use and understand the results of these tools. Accounting tools can seem complex when they are first used, but after walking through them step-by-step and practicing them, they can become an essential tool in working with executives and other administrators.

Accounting Basics Part 1: Application in Healthcare.

Accounting terminology and methods are essential parts of management and can be used to improve the efficacy of communication with other managers and executives. While learning these terms and methods can seem daunting, the rewards are well worth the effort. Accounting terminology can seem almost as complex as medical terminology: revenues, expenses, iRR, net pres- ent value, and profit. However, manag- ers and supervisors don't need to understand all of those terms, just those most commonly used. Once those basics have been mastered, they will provide sufficient background to understand the many forms, information requests, and questions accounting and finance lead- ers will provide and request. Imaging supervisors and directors can use these terms and methods to success- fully communicate with management about resources needed and their impact on the community and the bottom line of the organization. The reward for the time spent is well worth the effort.

Electronic structure and spectroscopic analysis of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ion pair.

Electronic and structural properties of the room temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulonyl)imide are studied using density functional theory (DFT) methods in addition to infrared and UV-vis spectroscopy. The DFT methods were conducted for both gas phase and solution phase using the integral equation formalism polarizable continuum model, while optical absorption experiments were conducted using neat and dilute methanol solutions. Three energetically similar conformers were obtained for each of the gas phase and solution phase DFT calculations. These multiple configurations were considered when analyzing the molecular interactions between the ion pair and for a molecular-level interpretation of the experimental IR and UV-vis spectroscopy data. Excitation energies of low-lying singlet excited states of the conformers were calculated with time-dependent DFT and experimentally with UV-vis absorption spectra. Difference density plots and excited-state calculations in the gas phase are found to be in good agreement with the experimental findings, while the implicit solvation model calculations adversely impacted the accuracy of the predicted spectra.

Measurements of cerebral microvascular blood flow, oxygenation, and morphology in a mouse model of whole-brain irradiation-induced cognitive impairment by two-photon microscopy and optical coherence tomography: evidence for microvascular injury in the cerebral white matter.

Whole-brain irradiation (WBI, also known as whole-brain radiation therapy) is a mainstay treatment modality for patients with multiple brain metastases. It is also used as a prophylactic treatment for microscopic tumors that cannot be detected by magnetic resonance imaging. WBI induces a progressive cognitive decline in ~ 50% of the patients surviving over 6 months, significantly compromising the quality of life. There is increasing preclinical evidence that radiation-induced injury to the cerebral microvasculature and accelerated neurovascular senescence plays a central role in this side effect of WBI. To better understand this side effect, male C57BL/6 mice were first subjected to a clinically relevant protocol of fractionated WBI (5 Gy, two doses per week, for 4 weeks). Nine months post the WBI treatment, we applied two-photon microscopy and Doppler optical coherence tomography to measure capillary red-blood-cell (RBC) flux, capillary morphology, and microvascular oxygen partial pressure (PO2) in the cerebral somatosensory cortex in the awake, head-restrained, WPI-treated mice and their age-matched controls, through a cover-glass-sealed chronic cranial window. Thanks to the extended penetration depth with the fluorophore - Alexa680, measurements of capillary blood flow properties (e.g., RBC flux, speed, and linear density) in the cerebral subcortical white matter were enabled. We found that the WBI-treated mice exhibited a significantly decreased capillary RBC flux in the white matter. WBI also caused a significant reduction in capillary diameter, as well as a large (although insignificant) reduction in segment density at the deeper cortical layers (e.g., 600-700 µm), while the other morphological properties (e.g., segment length and tortuosity) were not obviously affected. In addition, we found that PO2 measured in the arterioles and venules, as well as the calculated oxygen saturation and oxygen extraction fraction, were not obviously affected by WBI. Lastly, WBI was associated with a significant increase in the erythrocyte-associated transients of PO2, while the changes of other cerebral capillary PO2 properties (e.g., capillary mean-PO2, RBC-PO2, and InterRBC-PO2) were not significant. Collectively, our findings support the notion that WBI results in persistent cerebral white matter microvascular impairment, which likely contributes to the WBI-induced brain injury and cognitive decline. Further studies are warranted to assess the WBI-induced changes in brain tissue oxygenation and malfunction of the white matter microvasculature as well.

Embryonic overexpression of receptors for advanced glycation end-products by alveolar epithelium induces an imbalance between proliferation and apoptosis.

Receptors for advanced glycation end-products (RAGEs) are multiligand cell surface receptors highly expressed in the lung that contribute to alveolar epithelial cell differentiation during embryogenesis and the modulation of pulmonary inflammation during disease. When RAGEs are overexpressed throughout embryogenesis, severe lung hypoplasia ensues, culminating in perinatal lethality. However, the possible mechanisms that lead to the disappearance of pulmonary tissue remain unclear. A time course of lung organogenesis, commencing on Embryonic Day (E) 12.5, demonstrated that increased RAGE expression primarily alters lung morphogenesis beginning on E16.5. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunohistochemistry and immunoblotting for active caspase-3 confirmed a shift toward apoptosis in lungs from RAGE-overexpressing mice, compared with wild-type control mice. This observation supports previous work where electron microscopy identified the cellular blebbing of alveolar epithelium in embryonic RAGE-overexpressing mice. Assaying for NF-κB also revealed elevated nuclear translocation in lungs from transgenic mice compared with control mice. An RT-PCR assessment of genes regulated by NF-κB demonstrated the elevated expression of Fas ligand, suggesting increased activity of the Fas-mediated signal transduction pathway in which ligand-receptor interactions trigger cell death. These data provide evidence that the expression of RAGEs must be tightly regulated during homeostatic organogenesis. Further elucidations of the RAGE signaling potentially involved in cell-cycle abnormalities may provide insights into the progression of RAGE-mediated lung diseases.

Spectroscopic Investigation of Catalyst Inks and Thin Films Toward the Development of Ionomer Quality Control.

As the production of polymer electrolyte fuel cells expands, novel quality control methods must be invented or adapted in order to support expected rates of production. Ensuring the quality of deposited catalyst layers is an essential step in the fuel cell manufacturing process, as the efficiency of a fuel cell is reliant on the catalyst layer being uniform at both the target platinum loading and the target ionomer content. Implementing a quality control method that is sensitive to these aspects is imperative, as wasting precious metals and other catalyst materials is expensive, and represents a potential barrier to entry into the field for manufacturers experimenting with novel deposition processes. In this work, we analyzed catalyst inks to determine if their ionomer content could be quantized spectroscopically. Attenuated total reflection (ATR) Fourier transform infrared spectroscopic technique was investigated producing a signal proportional to the ionomer content. ATR spectroscopy was able to quantitatively differentiate samples in which the ionomer to carbon mass ratio (I/C) varied between 0.9 and 3.0. The I/C ratio was correlated to the measured ATR signal near the CF2 vibrational bands located between 1100 cm-1 and 1400 cm-1. The experimental results obtained constitute a step toward the development of novel quality control methodologies for catalyst inks utilized by the fuel cell industry.

Longitudinal In Vivo Changes in Radial Peripapillary Capillaries and Optic Nerve Head Structure in Non-Human Primates With Early Experimental Glaucoma.

Purpose: There is conflicting evidence regarding whether a loss of radial peripapillary capillaries (RPCs) precedes neuronal loss in glaucoma. We examined the time course of in vivo changes in RPCs, optic nerve head (ONH) structure, and retinal nerve fiber layer thickness (RNFLT) in experimental glaucoma (EG). Methods: Spectral domain optical coherence tomography images were acquired before and approximately every two weeks after inducing unilateral EG in nine rhesus monkeys to quantify mean anterior lamina cribrosa surface depth (ALCSD), minimum rim width (MRW), and RNFLT. Perfused RPC density was measured from adaptive optics scanning laser ophthalmoscope images acquired on the temporal half of the ONH. The time of first significant change was quantified as when values fell and remained outside of the 95% confidence interval established from control eyes. Results: Mean ALCSD and/or MRW were the first parameters to change in eight EG eyes. RPC density changed first in the ninth. At their first points of change, mean ALCSD posteriorly deformed by 100.2 ± 101.2 µm, MRW thinned by 82.3 ± 65.9 µm, RNFLT decreased by 25 ± 14 µm, and RPC density decreased by 4.5 ± 2.1%. RPC density decreased before RNFL thinning in 5 EG eyes. RNFLT decreased before RPC density decreased in two EG eyes, whereas two EG eyes had simultaneous changes. Conclusions: In most EG eyes, RPC density decreased before (or simultaneous with) a change in RNFLT, suggesting that vascular factors may play a role in axonal loss in some eyes in early glaucoma.

Optical measurement of microvascular oxygenation and blood flow responses in awake mouse cortex during functional activation.

The cerebral cortex has a number of conserved morphological and functional characteristics across brain regions and species. Among them, the laminar differences in microvascular density and mitochondrial cytochrome c oxidase staining suggest potential laminar variability in the baseline O2 metabolism and/or laminar variability in both O2 demand and hemodynamic response. Here, we investigate the laminar profile of stimulus-induced intravascular partial pressure of O2 (pO2) transients to stimulus-induced neuronal activation in fully awake mice using two-photon phosphorescence lifetime microscopy. Our results demonstrate that stimulus-induced changes in intravascular pO2 are conserved across cortical layers I-IV, suggesting a tightly controlled neurovascular response to provide adequate O2 supply across cortical depth. In addition, we observed a larger change in venular O2 saturation (ΔsO2) compared to arterioles, a gradual increase in venular ΔsO2 response towards the cortical surface, and absence of the intravascular "initial dip" previously reported under anesthesia. This study paves the way for quantification of layer-specific cerebral O2 metabolic responses, facilitating investigation of brain energetics in health and disease and informed interpretation of laminar blood oxygen level dependent functional magnetic resonance imaging signals.

Evaluating the global CpG methylation status of native DNA utilizing a bipartite split-luciferase sensor.

Epigenetic modifications play an essential role in the regulation of gene expression and ultimately cell fate. Methylation of cytosine at CpG dinucleotides (mCpG) is an important epigenetic mark that has been correlated with cancer when present at promoter sites of tumor suppressor genes. To develop a rapid methodology for the direct assessment of global levels of DNA methylation, we first interrogated the methyl-CpG binding domains (MBDs), the Kaiso family of Cys(2)-His(2) zinc fingers, and an SET- and RING-associated domain using a split-luciferase reassembly methodology. We identified MBD1 as the most selective domain for the discrimination between mCpG and CpG sites with over 90-fold selectivity. Utilizing a bipartite strategy, we constructed a purely methylation-dependent bipartite sensor for the direct detection of global levels of DNA methylation by attaching MBD1 domains to each of the split-luciferase halves. This new sensor was validated for the direct determination of genomic DNA methylation levels in in vitro studies without any intervening chemical or enzymatic processing of DNA. Finally, we demonstrated that this bipartite sensor can be utilized for monitoring dose-dependent changes in global levels of methylation in DNA from HeLa cells challenged with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor.

Wavefront sensorless adaptive optics ophthalmoscopy in the human eye.

Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor 'beacon' can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

Immunohistochemical detection and regulation of α5 nicotinic acetylcholine receptor (nAChR) subunits by FoxA2 during mouse lung organogenesis.

BACKGROUND: α5 nicotinic acetylcholine receptor (nAChR) subunits structurally stabilize functional nAChRs in many non-neuronal tissue types. The expression of α5 nAChR subunits and cell-specific markers were assessed during lung morphogenesis by co-localizing immunohistochemistry from embryonic day (E) 13.5 to post natal day (PN) 20. Transcriptional control of α5 nAChR expression by FoxA2 and GATA-6 was determined by reporter gene assays. RESULTS: Steady expression of α5 nAChR subunits was observed in distal lung epithelial cells during development while proximal lung expression significantly alternates between abundant prenatal expression, absence at PN4 and PN10, and a return to intense expression at PN20. α5 expression was most abundant on luminal edges of alveolar type (AT) I and ATII cells, non-ciliated Clara cells, and ciliated cells in the proximal lung at various periods of lung formation. Expression of α5 nAChR subunits correlated with cell differentiation and reporter gene assays suggest expression of α5 is regulated in part by FoxA2, with possible cooperation by GATA-6. CONCLUSIONS: Our data reveal a highly regulated temporal-spatial pattern of α5 nAChR subunit expression during important periods of lung morphogenesis. Due to specific regulation by FoxA2 and distinct identification of α5 in alveolar epithelium and Clara cells, future studies may identify possible mechanisms of cell differentiation and lung homeostasis mediated at least in part by α5-containing nAChRs.

Determining spherical lens correction for astronaut training underwater.

PURPOSE: To develop a model that will accurately predict the distance spherical lens correction needed to be worn by National Aeronautics and Space Administration astronauts while training underwater. The replica space suit's helmet contains curved visors that induce refractive power when submersed in water. METHODS: Anterior surface powers and thicknesses were measured for the helmet's protective and inside visors. The impact of each visor on the helmet's refractive power in water was analyzed using thick lens calculations and Zemax optical design software. Using geometrical optics approximations, a model was developed to determine the optimal distance spherical power needed to be worn underwater based on the helmet's total induced spherical power underwater and the astronaut's manifest spectacle plane correction in air. The validity of the model was tested using data from both eyes of 10 astronauts who trained underwater. RESULTS: The helmet's visors induced a total power of -2.737 D when placed underwater. The required underwater spherical correction (FW) was linearly related to the spectacle plane spherical correction in air (FAir): FW = FAir + 2.356 D. The mean magnitude of the difference between the actual correction worn underwater and the calculated underwater correction was 0.20 ± 0.11 D. The actual and calculated values were highly correlated (r = 0.971) with 70% of eyes having a difference in magnitude of <0.25 D between values. CONCLUSIONS: We devised a model to calculate the spherical spectacle lens correction needed to be worn underwater by National Aeronautics and Space Administration astronauts. The model accurately predicts the actual values worn underwater and can be applied (more generally) to determine a suitable spectacle lens correction to be worn behind other types of masks when submerged underwater.

Intrinsically photosensitive retinal ganglion cell-driven pupil responses in patients with traumatic brain injury.

Previous findings regarding intrinsically photosensitive retinal ganglion cell (ipRGC) function after traumatic brain injury (TBI) are conflicting. We examined ipRGC-driven pupil responses in civilian TBI and control participants using two pupillography protocols that assessed transient and adaptive properties: (1) a one second (s) long wavelength "red" stimulus (651 nm, 133 cd/m2) and 10 increasing intensities of 1 s short wavelength "blue" stimuli (456 nm, 0.167 to 167 cd/m2) with a 60 s interstimulus interval, and (2) two minutes of 0.1 Hz red stimuli (33 cd/m2), followed by two minutes of 0.1 Hz blue stimuli (16 cd/m2). For Protocol 1, constriction amplitude and the 6 s post illumination pupil response (PIPR) were calculated. For Protocol 2, amplitudes and peak velocities of pupil constriction and redilation were calculated. For Protocol 1, constriction amplitude and the 6 s PIPR were not significantly different between TBI patients and control subjects for red or blue stimuli. For Protocol 2, pupil constriction amplitude attenuated over time for red stimuli and potentiated over time for blue stimuli across all subjects. Constriction and redilation velocities were similar between groups. Pupil constriction amplitude was significantly less in TBI patients compared to control subjects for red and blue stimuli, which can be attributed to age-related differences in baseline pupil size. While TBI, in addition to age, may have contributed to decreased baseline pupil diameter and constriction amplitude, responses to blue stimulation suggest no selective damage to ipRGCs.

The Potential Role of Functional Motor Competence to Promote Physical Military Readiness: A Developmental Perspective.

Decreased physical fitness in military recruiting populations is problematic for the development of physical military readiness (PMR) and presents a threat to national security. The demonstration of low levels of fitness may be an indicator of a more foundational problem in the physical development of military recruits. We propose the development of functional motor competence (FMC) across childhood and adolescence as a necessary antecedent to advanced PMR training and military-specific tasks (i.e., rucking and obstacle course navigation) and as an integral part of sustained PMR. The development of FMC supports increases in cardiovascular and muscular endurance through repeated efforts performed during practice and in sport, as well as muscular power as many FMC movements mimic plyometrics in a strength in conditioning sense. We posit that an inadequate foundation in FMC will serve as a barrier to achieving sufficient PMR and combat success of the fighting force. We propose three possible solutions to ensure sufficient PMR levels through the implementation of developmentally appropriate FMC-based training. First would be promoting FMC-based training in junior reserve officer training corp and ROTC programs. Second would be a more global approach, on the scale of the National Defense Education Act, specifically focusing on promoting quality daily physical education that could reach millions of children. Third, individual branches could begin promoting the tenets of foundational FMC training concepts in their physical training manuals, which ideally would address FMC before and throughout basic training, as well as subsequent active duty training.