The Effect of Increasing Intracranial Pressure on Ocular Vestibular-Evoked Myogenic Potential Frequency Tuning.

OBJECTIVE Ocular vestibular-evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. The authors sought to investigate whether posture-induced increase of the intracranial pressure (ICP) modulated oVEMP frequency tuning, that is, the amplitude ratio between 500-Hz and 1000-Hz stimuli. DESIGN Ten healthy subjects were enrolled in this study. The subjects were positioned in the horizontal plane (0 degree) and in a 30-degree head-downwards position to elevate the ICP. In both positions, oVEMPs were recorded using 500-Hz and 1000-Hz air-conducted tone bursts. RESULTS When tilting the subject from the horizontal plane to the 30-degree head-down position, oVEMP amplitudes in response to 500-Hz tone bursts distinctly decreased (3.40 μV versus 2.06 μV; p < 0.001), whereas amplitudes to 1000 Hz were only slightly diminished (2.74 μV versus 2.48 μV; p = 0.251). Correspondingly, the 500/1000-Hz amplitude ratio significantly decreased when tilting the subjects from 0- to 30-degree inclination (1.59 versus 1.05; p = 0.029). Latencies were not modulated by head-down position. CONCLUSIONS Increasing ICP systematically alters oVEMPs in terms of absolute amplitudes and frequency tuning characteristics. oVEMPs are therefore in principle suited for noninvasive ICP monitoring.

Assessment of cone beam computed tomography techniques for imaging lung damage in mice in vivo

Lung damage is a common side effect of chemotherapeutic drugs such as bleomycin. This study used a bleomycin mouse model which simulates the lung damage observed in humans. Noninvasive, in vivo cone-beam computed tomography (CBCT) was used to visualize and quantify fibrotic and inflammatory damage over the entire lung volume of mice. Bleomycin was used to induce pulmonary damage in vivo and the results from two CBCT systems, a micro-CT and flat panel CT (fpCT), were compared to histologic measurements, the standard method of murine lung damage quantification. Twenty C57BL/6 mice were given either 3 U/kg of bleomycin or saline intratracheally. The mice were scanned at baseline, before the administration of bleomycin, and then 10, 14, and 21 days afterward. At each time point, a subset of mice was sacrificed for histologic analysis. The resulting CT images were used to assess lung volume. Percent lung damage (PLD) was calculated for each mouse on both the fpCT (PLDfpcT) and the micro-CT (PLDμCT). Histologic PLD (PLDH) was calculated for each histologic section at each time point (day 10, n = 4; day 14, n = 4; day 21, n = 5; control group, n = 5). A linear regression was applied to the PLDfpCT vs. PLDH, PLDμCT vs. PLDH and PLDfpCT vs. PLDμCT distributions. This study did not demonstrate strong correlations between PLDCT and PLDH. The coefficient of determination, R, was 0.68 for PLDμCT vs. PLDH and 0.75 for the PLD fpCT vs. PLDH. The experimental issues identified from this study were: (1) inconsistent inflation of the lungs from scan to scan, (2) variable distribution of damage (one histologic section not representative of overall lung damage), (3) control mice not scanned with each group of bleomycin mice, (4) two CT systems caused long anesthesia time for the mice, and (5) respiratory gating did not hold the volume of lung constant throughout the scan. Addressing these issues might allow for further improvement of the correlation between PLDCT and PLDH. ^

Ambulatory blood pressure and physical activity in heart failure

Background. Ambulatory blood pressure (ABP) measurement is a means of monitoring cardiac function in a noninvasive way, but little is known about ABP in heart failure (HF) patients. Blood pressure (BP) declines during sleep as protection from consistent BP load, a phenomenon termed "dipping." The aims of this study were (1) to compare BP dipping and physical activity between two groups of HF patients with different functional statuses and (2) to determine whether the strength of the association between ambulatory BP and PA is different between these two different functional statuses of HF. ^ Methods. This observational study used repeated measures of ABP and PA over a 24-hour period to investigate the profiles of BP and PA in community-based individuals with HF. ABP was measured every 30 minutes by using a SpaceLabs 90207, and a Basic Motionlogger actigraph was used to measure PA minute by minute. Fifty-six participants completed both BP and physical activity for a 24-hour monitoring period. Functional status was based on New York Heart Association (NYHA) ratings. There were 27 patients with no limitation of PA (NYHA class I HF) and 29 with some limitation of PA but no discomfort at rest (NYHA class II or III HF). The sample consisted of 26 men and 30 women, aged 45 to 91 years (66.96 ± 12.35). ^ Results. Patients with NYHA class I HF had significantly greater dipping percent than those with NYHA class II/III HF after controlling their left ventricular ejection fraction (LVEF). In a mixed model analysis (PROC MIXED, SAS Institute, v 9.1), PA was significantly related to ambulatory systolic and diastolic BP and mean arterial pressure. The strength of the association between PA and ABP readings was not significantly different for the two groups of patients. ^ Conclusions. These preliminary findings demonstrate differences between NYHA class I and class II/III of HF in BP dipping status and ABP but not PA. Longitudinal research is recommended to improve understanding of the influence of disease progression on changes in 24-hour physical activity and BP profiles of this patient population. ^ Key Words. Ambulatory Blood Pressure; Blood Pressure Dipping; Heart Failure; Physical Activity. ^

NRAS and BRAF mutations in primary cutaneous melanoma: A comparison of mutation rates between radial and vertical growth phases in individual tumors

Primary cutaneous melanoma is a cancer arising from melanocytes in the skin. In recent decades the incidence of this malignancy has increased significantly. Mortality rates are high for patients with tumors measuring over a few millimeters in thickness. Response rates to conventional radiation and chemotherapy are very low in patients with metastatic melanoma. New therapies targeting melanoma’s aberrant cell signaling pathways such as the MAP Kinase pathway are being developed. Mutations of NRAS and BRAF genes are quite common in cutaneous melanoma and lead to constitutive activation of the MAP Kinase pathway. This study tests the hypothesis that NRAS and BRAF mutations increase as a tumor progresses from the noninvasive radial growth phase (RGP) to the invasive vertical growth phase (VGP). Laser capture microdissection was used to obtain separate, pure tumor DNA samples from the RGP and VGP of thirty primary cutaneous melanomas. PCR was used to amplify NRAS exon 2 and BRAF exon 15 tumor DNA. The amplified DNA was sequenced and analyzed for mutations. An overall mutation rate of 74% was obtained for the twenty-three melanomas in which there were complete sequence results. With the exception of one melanoma NRAS and BRAF mutations were mutually exclusive. All seven NRAS exon 2 mutations involved codon 61. Three of these melanomas had mutations in both the RGP and VGP. The remaining four tumors were wild type for NRAS exon 2 in the RGP but mutated in the VGP. Of the fifteen BRAF exon 15 mutated melanomas all but one involved codon 600. Twelve of the fifteen BRAF exon 15 mutations were the T1799A type. Nine of the fifteen BRAF mutated tumors had the same mutation in both the RGP and VGP. Five of fifteen melanomas had wild type RGP DNA and BRAF exon 15 mutated VGP DNA. A single melanoma had BRAF exon 15 mutated DNA in the RGP and wild type DNA in the VGP. Overall, these results suggest a trend toward the acquisition of NRAS and BRAF mutations as cutaneous melanomas change from a noninvasive to an invasive, potentially deadly cancer.^

Maximal exercise hemodynamics and risk of mortality in apparently healthy men and women

The use of exercise electrocardiography (ECG) to detect latent coronary heart disease (CHD) is discouraged in apparently healthy populations because of low sensitivity. These recommendations however, are based on the efficacy of evaluation of ischemia (ST segment changes) with little regard for other measures of cardiac function that are available during exertion. The purpose of this investigation was to determine the association of maximal exercise hemodynamic responses with risk of mortality due to all-causes, cardiovascular disease (CVD), and coronary heart disease (CHD) in apparently healthy individuals. Study participants were 20,387 men (mean age = 42.2 years) and 6,234 women (mean age = 41.9 years) patients of a preventive medicine center in Dallas, TX examined between 1971 and 1989. During an average of 8.1 years of follow-up, there were 348 deaths in men and 66 deaths in women. In men, age-adjusted all-cause death rates (per 10,000 person years) across quartiles of maximal systolic blood pressure (SBP) (low to high) were: 18.2, 16.2, 23.8, and 24.6 (p for trend $<$0.001). Corresponding rates for maximal heart rate were: 28.9, 15.9, 18.4, and 15.1 (p trend $<$0.001). After adjustment for confounding variables including age, resting systolic pressure, serum cholesterol and glucose, body mass index, smoking status, physical fitness and family history of CVD, risks (and 95% confidence interval (CI)) of all-cause mortality for quartiles of maximal SBP, relative to the lowest quartile, were: 0.96 (0.70-1.33), 1.36 (1.01-1.85), and 1.37 (0.98-1.92) for quartiles 2-4 respectively. Similar risks for maximal heart rate were: 0.61 (0.44-0.85), 0.69 (0.51-0.93), and 0.60 (0.41-0.87). No associations were noted between maximal exercise rate-pressure product mortality. Similar results were seen for risk of CVD and CHD death. In women, similar trends in age-adjusted all-cause and CVD death rates across maximal SBP and heart rate categories were observed. Sensitivity of the exercise test in predicting mortality was enhanced when ECG results were evaluated together with maximal exercise SBP or heart rate with a concomitant decrease in specificity. Positive predictive values were not improved. The efficacy of the exercise test in predicting mortality in apparently healthy men and women was not enhanced by using maximal exercise hemodynamic responses. These results suggest that an exaggerated systolic blood pressure or an attenuated heart rate response to maximal exercise are risk factors for mortality in apparently healthy individuals. ^

Improved Techniques for Acquisition and Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Detecting Vascular Permeability in the Central Nervous System

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In addition, an original multi-step curve fitting procedure was developed to increase the accuracy of T1 estimation. A view sharing acquisition method was implemented to increase temporal resolution, and a novel normalization method was introduced to reduce image artifacts. Finally, a new clustering algorithm was developed to reduce apparent noise in the DCE-MRI data. The performance of these proposed methods was verified by simulations and phantom studies. As part of this work, the proposed techniques were applied to an in vivo DCE-MRI study of experimental spinal cord injury (SCI). These methods have shown robust results and allow quantitative assessment of regions with very low vascular permeability. In conclusion, applications of the improved DCE-MRI acquisition and analysis methods developed in this thesis work can improve the accuracy of the DCE-MRI results.

External assessment of myocardial glucose metabolism with $\sp{18}$F-2 -deoxy-2 -fluoro-D-glucose

Despite the popularity of the positron emitting glucose analog, ($\sp{18}$F) -2-deoxy-2-fluoro-D-glucose (2FDG), for the noninvasive "metabolic imaging" of organs with positron emission tomography (PET), the physiological basis for the tracer has not been tested, and the potential of 2FDG for the rapid kinetic analysis of altered glucose metabolism in the intact heart has not been fully exploited. We, therefore, developed a quantitative method to characterize metabolic changes of myocardial glucose metabolism noninvasively and with high temporal resolution.^ The first objective of the work was to provide direct evidence that the initial steps in the metabolism of 2FDG are the same as for glucose and that 2FDG is retained by the tissue in proportion to the rate of glucose utilization. The second objective was to characterize the kinetic changes in myocardial glucose transport and phosphorylation in response to changes in work load, competing substrates, acute ischemia and reperfusion, and the addition of insulin. To assess changes in myocardial glucose metabolism isolated working rat hearts were perfused with glucose and 2FDG. Tissue uptake of 2FDG and the input function were measured on-line by external detection. The steady state rate of 2FDG phosphorylation was determined by graphical analysis of 2FDG time-activity curves.^ The rate of 2FDG uptake was linear with time and the tracer was retained in its phosphorylated form. Tissue accumulation of 2FDG decreased within seconds with a reduction in work load, in the presence of competing substrates, and during reperfusion after global ischemia. Thus, most interventions known to alter glucose metabolism induced rapid parallel changes in 2FDG uptake. By contrast, insulin caused a significant increase in 2FDG accumulation only in hearts from fasted animals when perfused at a sub-physiological work load. The mechanism for this phenomenon is not known but may be related to the existence of two different glucose transporter systems and/or glycogen metabolism in the myocardial cell.^ It is concluded that (1) 2FDG traces glucose uptake and phosphorylation in the isolated working rat heart; and (2) early and transient kinetic changes in glucose metabolism can be monitored with high temporal resolution with 2FDG and a simple positron coincidence counting system. The new method has revealed transients of myocardial glucose metabolism, which would have remained unnoticed with conventional methods. These transients are not only important for the interpretation of glucose metabolic PET scans, but also provide insights into mechanisms of glucose transport and phosphorylation in heart muscle. ^

(Table 1) Dissolved organic carbon, water temperature and conductivity in three subarctic ponds near Kilpisjärvi, North Finland

Daphnia was collected from five subarctic ponds which differed greatly in their DOC contents and, consequently, their underwater light (UV) climates. Irrespective of which Daphnia species was present, and contrary to expectations, the ponds with the lowest DOC concentrations (highest UV radiation levels) contained Daphnia with the highest eicosapentaenoic acid (EPA) concentrations. In addition, EPA concentrations in these Daphnia generally decreased in concert with seasonally increasing DOC concentrations. Daphnia from three of the ponds was also tested for its tolerance to solar ultraviolet radiation (UVR) with respect to survival. Daphnia pulex from the clear water pond showed, by far, the best UV-tolerance, followed by D. longispina from the moderately humic and D. longispina from the very humic pond. In addition, we measured sublethal parameters related to UV-damage such as the degree to which the gut of Daphnia appeared green (as a measure of their ability to digest algae), and whether their guts appeared damaged. We developed a simple, noninvasive scoring system to quantify the proportion of the gut in which digestive processes were presumably active. This method allowed repeated measurement of the same animals over the course of the experiment. We demonstrated, for the first time, that sublethal damage of the gut precedes mortality caused by exposure to UVR. In a parallel set of experiments we fed UV-exposed and non-exposed algae to UV-exposed and non-exposed daphnids. UVR pretreatment of algae enhanced the negative effects of exposure to natural solar UV-irradiation in Daphnia. These UV-related effects were generally not specific to the species of Daphnia.

(Table 1) Enantiomer fractions of egg yolk and plasma samples from Svalbard glaucous gulls (Larus hyperboreus)

Glaucous gulls (Larus hyperboreus) and their eggs from Svalbard (Norwegian Arctic) have been used as biomonitors of contaminants in the marine environment. In this study, the enantiomer fractions (EFs) of chiral chlordanes and atropisomeric polychlorinated biphenyl (PCB) congeners were determined in the blood plasma of adult male and female glaucous gulls from three breeding colonies in Svalbard. Plasma EFs were similar in magnitude and direction to EFs previously reported in glaucous gulls from other arctic food webs, suggesting overall similarities in the biochemical processes influencing the EFs of bioaccumulated organochlorine (OC) contaminants within the food webs at those locations. Additionally, EFs in yolk of eggs collected concurrently from within the same nesting colonies varied with location, laying date, and OC concentrations, and may be influenced by changes in the local feeding ecology between those colonies. No differences were found between the EFs for any analyte in female gulls compared to those found in egg yolk, indicating that processes involved in the maternal transfer of chlordanes and PCBs to eggs do not modulate the stereochemical ratio between enantiomers. Therefore, the use of eggs as a valuable and noninvasive means of OC biomonitoring may also extend to enantiomer compositions in glaucous gulls, and perhaps also in other seabird species from arctic regions.

Spectral reflectance of ODP Leg 178 holes

The routine use of spectrophotometry on the sediment surfaces of archive halves of each section during the onboard sedimentological core description process is a great stride toward development of real-time noninvasive characterization of deep-sea sediments. Spectral reflectance data have been used so far for mineral composition studies as well as for lithostratigraphic correlation between sites (Balsam and Deaton, 1991; Balsam et al., 1997; Mix et al., 1995; Ortiz et al., 1999). Their results demonstrate that spectrophotometry can estimate CaCO3 content by using the 4.65-, 5.25-, and 5.55-µm wavelength spectrums. A detailed overview of various other noninvasive methods is given in Ortiz and Rack (1999). The purpose of this study is to test whether spectrophotometry in the visible band can be used as a tool to gather further information about grain-size variation, sorting, compaction, and porosity, which are directly linked to the sedimentation process. From remote sensing data analyses, it is known that diffuse spectral reflectance data in the visible band in the wavelength window of 7.0-6.5 µm are sensitive to grain-size variations. It appears that a relationship between grain size and signal absorption exists only in this wavelength window. (e.g., Clark, 1999; Gaffey, 1986; Gaffey et al., 1993). Variations in grain size during a sedimentation process are linked to depositional energy, which affects sorting, compaction, and porosity of sediment deposits. As an example, we study here the spectrophotometric data of the sedimentary sequence of Hole 1098C, which was deposited under widely varying environmental conditions. Alternating turbidite and finely laminated sediments were recovered from Hole 1098C. The turbidites are related to a high depositional energy environment; the finely laminated sediments are related to a low depositional energy environment. Data from Hole 1098C were therefore used to test whether the spectral reflectance data can provide a proxy for these different depositional environments.

Calcium carbonate stratigraphy of ODP Site 177-1090

A total of 776 sediment samples were measured for percent CaCO3 using a coulometer. These data are compared with percent blue reflectance (450-550 nm) measured with the Oregon State University split-core analysis track. In previous studies percent blue reflectance has been an excellent proxy for percent CaCO3 and in this study shows many of the main depositional trends (i.e., a 100-k.y. cycle, with a 55% reflectance range is evident in the upper 900 k.y., underlain by sediments exhibiting a 40-k.y. cycle with only a 30% reflectance range). Between ~21 and 5 Ma the average percent reflectance decreases from ~35% to ~8%. A similar decrease is also recorded between ~24 and 22 Ma. Percent CaCO3 trends closely match those of the percent blue spectral reflectance. This is especially well shown in the 100-k.y. cyclicity and in the interval between 24.5 and 21.5 Ma. In both intervals CaCO3 analyses are abundant. An exception occurs in the interval between 2 and 5 meters composite depth (~193 and 240 k.y.). There, percent CaCO3 and percent reflectance are out of phase. The lack of agreement is not likely to be due to a very wet core, in which water would dominate the spectral reflectance instead of sediment, or to problems with the composite depth slice. The discrepancy remains unexplained and provides clear evidence that when noninvasive measurements are used as proxies for chemical measurements they must be substantiated by the actual chemical or physical measurements.

Inspección técnica de la presa Santa Marta, mediante medidas subacuáticas de potencial espontáneo

Las filtraciones de agua, con la consecuente erosión interna en presas de materiales sueltos, es una de las causas principales de fallos y accidentes. Las consecuencias del fallo de estas estructuras, pueden ser, pérdidas tanto económicas como de vidas humanas. Por lo cual en este proyecto se describe la aplicación de un método de prospección geofísica no invasiva, medidas de potencial espontáneo, para detectar posibles filtraciones de agua en el cuerpo de la presa. El flujo de agua a través de un material poroso y permeable crea un campo de potencial eléctrico de una magnitud de decenas o centenas de milivoltios, el cual puede ser medido y así detectar infiltraciones de agua en presas de materiales sueltos. Se ha aplicado esta técnica en la Presa Santa Marta, y mediante una interpretación cualitativa de los datos medidos, tomados en la cara aguas arriba de la presa (medidas subacuáticas), se logró identificar un flujo de agua vertical y otro subhorizontal, que estaban ingresando en el cuerpo de la presa, los cuales estaban causando erosión interna y la formación de una tubificación. ABSTRACT Water leakages and internal erosion in embankment dams is one of the main causes of failures and accidents. The consequences of the failure of these structures may cause losses both, economical and of human lives. Therefore, this project describes the application of a noninvasive geophysical prospecting method, self potential measurements, to detect water leakages in the body of the dam. Water flow through a porous and pervious medium creates an electric potential field with a magnitude of tens or hundreds of milivolts, which can be measured and thus detect water leakage in embankment dams. This technique has been applied to the Santa Marta dam, and through a qualitative self potential data interpretation, of the measurements obtained in an upstream direction (underwater measurements), a vertical and sub horizontal water flows entering in the body dam were identified, which were causing internal erosion and developing a piping

Observation and Detection of Underground Cellars in the Duero Basin By GNSS, Lidar and Ground Penetrating Radar Techniques

The underground cellars that appear in different parts of Spain are part of an agricultural landscape dispersed, sometimes damaged, others at risk of disappearing. This paper studies the measurement and display of a group of wineries located in Atauta (Soria), in the Duero River corridor. It is a unique architectural complex, facing rising, built on a smooth hillock as shown in Fig. 1. These constructions are excavated in the ground. The access to the cave or underground cellar has a shape of a narrow tube or down gallery. Immediately after, this space gets wider. There, wine is produced and stored [1]. Observation and detection of the underground cellar, both on the outside and underground, it is essential to make an inventory of the rural patrimony [2]. The geodetection is a noninvasive technique, adequate to accurately locate buried structures in the ground. Works undertaken include topographic work with the LIDAR techniques and integration with data obtained by GNSS and GPR.

Infrared thermography to quantify the risk of breast cancer.

From the last decades, infrared thermography is quite often associated with things other than clinical medicine. For example, the chemical, automobile, aeronautic industries and civil engineering. However, thermography is where infrared images of the breast are analyzed by board certified thermographers and an abnormal thermogram is reported as the significant risk for the existence of breast tumor (Ng, 2009). Thermography is a painless, noninvasive, no radiation, as well as being cheaper and faster, easier access. The aim of this review was to identify the views of clinicians on the use of thermography for quantifying the risk of breast cancer. We used articles published recently in a reliable database. Thermography has been convicted over the years; it has been labeled by subjective interpretation. Most of the reviewed articles agree that mammography is currently the main examination chosen by doctors for the screening of breast cancer (Acharya et al., 2010; Kennedy et al., 2009). However, several studies have reported promising results for the technique (Wang et al., 2010). Additionally, some authors suggest that thermography is complementary to other diagnostic methods, and that the best strategy for the early detection of breast cancer would be to use them together (Kennedy et al., 2009; Hersh, 2004). The combination of thermal imaging with other tests would increase accuracy, sensitivity and specificity of the evaluation and allow a better quantification of the risk of breast cancer.

Effect of yoga and swimming on body temperature of pregnant women

Physical activity for pregnant women should be controlled and adapted in order to minimize the risk of loss of balance and fetal trauma (Davies, Wolfe, Mottola, y MacKinnon, 2003). Noninvasive technologies are required for understanding better the effects of physical activity on pregnant women. Infrared thermography allows, remotely, securely and without any contact, to measure and display accurate temperatures on the human skin.