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All children enjoy inflating balloons and twisting them into different shapes and animals. Snapping the balloon into two separate compartments is a necessary step that bears resemblance to the pinch-off phenomenon for water droplet detached from the faucet. In addition to testing whether balloons exhibit the properties of self-similarity and memory effect that are often associated with the latter event, we determine their phase diagram by experiments. It turns out that a common party balloon does not just snap. They in fact can assume five more shapes, i.e., straight, necking, wrinkled, helix, and supercoil, depending on the twist angle and ratio of its length and diameter. Moreover, history also matters due to their prominent hysteresis. One may shift the phase boundary or/and reshuffle the phases by untwisting or lengthening the balloon at different twist angle and initial length. Heuristic models are provided to obtain analytic expressions for the phase boundaries., 5 pages and 4 figures

The Neolithic transition began the spread of early agriculture throughout Europe through interactions between farmers and hunter-gatherers about 10,000 years ago. Archeological evidence produced by radiocarbon dating indicates that the expanding velocity of farming is roughly constant all over Europe. Theoretical understanding of such evidence has been performed from mathematical modeling viewpoint. However, the expanding velocity determined by existing modeling approaches is faster than the observed velocity. For understanding this difference, we propose a three-component reaction-diffusion system which consists of two different types of farmers (sedentary and migratory) and hunter-gatherers from the viewpoint of the influence of farming technology. Our purpose is to study the relation between the expanding velocity of farmers and the farming technology parameter (say, [Formula: see text]). In this paper, we mainly focus on the one-dimensional traveling wave solution with minimal velocity and show that the minimal velocity decreases, as [Formula: see text] increases. This can be compatible with the observed velocity when farming technology is developed. Our results suggest that the reason for the slowdown of the Neolithic transition might be related to the increase in the development of farming technology.

We study the responses of fluid-immersed soft hydrogel spheres that are sheared under controlled volume fractions. Slippery, deformable particles along with the density-matched interstitial fluid are sandwiched between two opposing rough cones, allowing studies for a wide range of volume fraction $\phi$ both above and below the jamming of granular suspension. We utilize sudden cessations of shearing, accompanied by refraction-matched internal imaging, to supplement the conventional flow-curve measurements. At sufficiently high volume fractions, the settling of particles after the cessations exhibits a continuous yet distinct transition over the change of shear rate. Such changes back out the qualitative difference in the state of flowing prior to the cessations: the quasi-static yielding of a tightly packed network, as opposed to the rapid sliding of particles mediated by the interstitial fluid whose dynamics depends on the driving rate. In addition, we determine the solid-fluid transition using two independent methods: the extrapolation of stress residues and the estimated yield stress from high values of $\phi$, and the settling of particles upon shear cessations as $\phi$ goes across the transition. We also verify the power law on values of characteristic stress with respect to the distance from jamming $\phi - \phi_c$, with an exponent close to 2. These results demonstrate a multitude of relaxation timescales behind the dynamics of soft particles, and provoke questions on how we extend existing paradigms on the flow of a densely packed system when the softness is actively involved., Comment: Soft Matter, 2020

The ordered bicontinuous double diamond (OBDD) structure has long been believed to be an unstable ordered network nanostructure, which is relative to the ordered bicontinuous double gyroid (OBDG) structure for diblock copolymers. Using electron tomography, we present the first real-space observation of the thermodynamically stable OBDD structure in a diblock copolymer composed of a stereoregular block, syndiotactic polypropylene-block-polystyrene (sPP-b-PS), in which the sPP tetrapods are interconnected via a bicontinuous network with Pn3̄m symmetry. The OBDD structure underwent a thermally reversible order-order transition (OOT) to OBDG upon heating, and the transition was accompanied with a slight reduction of domain spacing, as demonstrated both experimentally and theoretically. The thermodynamic stability of the OBDD structure was attributed to the ability of the configurationally regular sPP block to form helical segments, even above its melting point, as the reduction of internal energy associated with the helix formation may effectively compensate the greater packing frustration in OBDD relative to that in the tripods of OBDG.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor β (TGF-β) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

Medium-format digital cameras are a useful tool in airborne lidar missions to produce digital ortho-images. This study investigates the quality of digital elevation models (DEMs) and digital surface models (DSMs) derived from such cameras. An image-matching strategy is used to produce height information from highly overlapping images and the quality of the derived height information is analysed using synchronous lidar point clouds as the reference data. The evaluation focused on various types of land cover and DEM generation methods. The RMSE between lidar and image-derived height information for two datasets was 0·054% and 0·027% of the flying height in flat, bare-earth areas, but studies with manually edited vegetated areas using stereo photogrammetry revealed high uncertainties, especially in steep terrain. Resume Les appareils photo numeriques moyen format sont appropries pour la production d'ortho-images lors de missions lidar aeroportees. Cette etude s'interesse a la qualite des MNE (modeles numeriques d'elevation) et MNS (modeles numeriques de surface) obtenus a partir de tels instruments. Une strategie d'appariement d'images est mise en œuvre pour produire une information altimetrique a partir d'images a fort recouvrement et la qualite de l'altitude obtenue est analysee en utilisant les nuages de points lidar comme des donnees de reference. L'evaluation porte sur plusieurs types d'occupation du sol et plusieurs methodes de production de MNE. Les erreurs moyennes quadratiques obtenues, pour deux jeux de donnees, entre les altitudes issues du lidar et des images, sont de 0·054% et 0·027% de la hauteur de vol sur des zones plates et degagees, mais des etudes conduites manuellement en utilisant des donnees de stereophotogrammetrie sur des zones couvertes de vegetation mettent en evidence des incertitudes elevees, notamment en presence de fortes pentes. Zusammenfassung Mittelformatige Digitalkameras werden bei flugzeuggestutztem Laserscanning (LIDAR) zur Produktion digitaler Orthophotos eingesetzt. In dieser Studie wird die Qualitat von Digitalen Hohenmodellen (engl. DEMs) und Digitalen Oberflachenmodellen (engl. DSMs), die aus solchen Kameras abgeleitet werden untersucht. Eine Bildzuordnungsstrategie zur Ableitung von Hoheninformation aus stark uberlappenden Bildern wird mit Hilfe eines Referenzdatensatzes aus synchron aufgenommenen LIDAR-Punktwolken analysiert. Die Analyse umfasste dabei verschiedene Landschaftstypen und Methoden zur Produktion digitaler Hohenmodelle. Der RMSE Wert zwischen LIDAR-Punktwolken und Punktwolken aus Bildzuordnung zweier Datensatze lag bei 0·054% bzw. 0·027% der Flughohe in flachen Gebieten ohne Bewuchs. Studien mit manuell editierten bewachsenen Gebieten legten jedoch hohe Messunsicherheiten, speziell in steilem Gelande, offen. Resumen Las camaras digitales de medio formato son herramientas utiles para producir ortoimagenes en vuelos lidar. En este estudio se investiga la calidad de modelos de elevacion digitales (MEDs) y de modelos de superficie (MDSs) derivados de estas camaras. La altura se determina mediante tecnicas de correspondencia de imagenes, las cuales tienen un gran recubrimiento. Su calidad se determina usando nubes de puntos lidar simultaneos como referencia. La evaluacion se centra en los distintas cubiertas del suelo y los metodos de generacion de MEDs. El error RMS entre las alturas lidar y las derivadas de las imagenes en dos conjuntos de datos es de 0·054% y 0·027% de la altura de vuelo en terreno llano y descubierto. Estudios con edicion estereoscopica manual en areas con vegetacion muestran grandes incertidumbres, especialmente en zonas con pendiente.

We study experimentally a short chain of $N(\ensuremath{\le}8)$ loosely connected spheres bouncing against a horizontal surface that vibrates sinusoidally at intensity $\mathrm{\ensuremath{\Gamma}}$. Distinct states are identified: a base state of uniform bouncing in-sync with the substrate prevails at low values of $\mathrm{\ensuremath{\Gamma}}$, whereas increasing $\mathrm{\ensuremath{\Gamma}}$ can induce transitions to two excited states with appreciable storage of energy around one or both ends of the chain. We find that, in a transitional window of $\mathrm{\ensuremath{\Gamma}}$, the chain can even switch spontaneously among states, resolving the mystery why different modes of motion can be initiated at the same position in our previous work along a gradient of vibration [Phys. Rev. Lett. 112, 058001 (2014)]. Preliminary interpretations on the parametric dependences and the optimal frequency window for seeing these transitions are offered, based on the microscopic and statistical evidence in our experiments up to date.

Liquid foams are an extreme case of multiphase flow systems: capable of flow despite a very high dispersed phase volume fraction, yet exhibiting many characteristics of not only viscoelastic materials but also elastic solids. The non-trivial, well-defined geometry of foam bubbles is at the heart of a plethora of dynamical processes on widely varying length and time scales. We highlight recent developments in foam drainage (liquid dynamics) and foam rheology (flow of the entire gas–liquid system), emphasizing that many poorly understood features of other materials have precisely defined and quantifiable analogues in aqueous foams, where the only ingredients are well-known material parameters of Newtonian fluids and bubble geometry, together with subtle but important information on the surface mobility of the foam. Not only does this make foams an ideal model system for the theorist, but also an exciting object for experimental studies, in which dynamical processes span length scales from nanometres (thin films) to metres (foam continuum flows) and time scales from microseconds (film rupture) to minutes (foam rheology).

We investigate experimentally the steady flows in a cylinder containing two immiscible liquids, with the primary fluid being driven by the upper boundary rotating at constant speeds. The system exhibits interesting interplays between the flow fields and the morphology of the interface, with evidence showing that the remarkable flattop structure is a consequence of the vortex breakdown discovered decades ago, and that the deformability of the interface also feedbacks positively to the development of the vortices. Monitoring the topological structure of the flow fields defines the base states and transitions behind the morphology, whereas our survey over different aspect ratios also reveals rich phenomena of surface instabilities accompanying these steady states.

The kidney is an important site of endothelin&hyphen;1 &lpar;ET&hyphen;1&rpar; production and is particularly susceptible to ET&hyphen;1 action. Infusion of ET&hyphen;1 in rats induces both functional and morphological alterations in the kidneys. Increased plasma level of ET&hyphen;1 has been reported in patients with chronic renal failure. However, there are still no reports on the plasma and urinary ET&hyphen;1 levels in patients with focal segmental glomerulosclerosis &lpar;FSGS&rpar;. In the present study, we have measured the plasma concentration and urinary excretion rate of ET&hyphen;1 in 15 patients with nephrotic syndrome due to FSGS, and observed the serial changes of plasma and urinary ET&hyphen;1 in nephrotic rats with FSGS, induced by repeated injection with puromycin aminonucleoside &lpar;PAN&rpar;. ET&hyphen;1 was measured with radioimmunoassay. The results showed that plasma ET&hyphen;1 concentration in FSGS patients was significantly higher than in normal controls &lpar;P < 0.05&rpar;, and that urinary ET&hyphen;1 excretion rate was also significantly higher in FSGS patients than in normal controls &lpar;P < 0.01&rpar;. In FSGS patients, the plasma and urinary ET&hyphen;1 was significantly correlated &lpar;P < 0.05&rpar;, and the urinary ET&hyphen;1 excretion rate was significantly correlated with the amount of proteinuria &lpar;P < 0.05&rpar; and the glomerular sclerosing score &lpar;P < 0.01&rpar;. In the ten rats with PAN&hyphen;induced FSGS, serial examination showed a significant increase in plasma ET&hyphen;1 after 8 weeks of injections, while the urinary ET&hyphen;1 excretion rate showed a biphasic increase that showed a peak after 4 to 6 weeks. The same changes in plasma and urinary ET&hyphen;1 levels were not observed in control rats injected with normal saline at the same frequency. Our results suggest that ET&hyphen;1 may be involved in the pathogenesis of FSGS in both humans and rats. J. Clin. Lab. Anal. 15:59–63, 2001. © 2001 Wiley&hyphen;Liss, Inc.

We report our experimental work on a one-dimensional gradient of vibration with a short granular chain. The system exhibits transitions of ratcheting dynamics from passive monotonic creeping against the gradient, to rapid stochastic head swinging with a reversed bias in its direction, and to seemingly random fluctuations. The spontaneously emerged spatial pattern reflects bifurcations of the state of the chain. Evidence from counterpart experiments using uniform vibrations confirms a nonmonotonic development of accessible modes behind the transitions, whereas the reversed ratcheting reflects an interesting dialogue between the size of the object and the spatial gradient.

Both optic nerves were obtained at autopsy from a 28-year-old man with a 2 year history of idiopathic intracranial hypertension who had undergone bilateral optic nerve sheath decompression 14 days before death. Histopathological and ultrastructural examination of the tissue revealed fibroblasts localised to the sites of fenestration. Adipose tissue was also adherent to the optic nerve pia in areas of incised dura. No patent fistula site was observed. It was concluded that filtration of cerebrospinal fluid after optic nerve sheath decompression may occur through an enclosed bleb of fibrosis rather than through an open fistula.

There is both clinical and histopathologic evidence for peripheral visual field loss and optic nerve degeneration in longstanding papilledema due to idiopathic intracranial hypertension (IIH). The purpose of this study was to look at the extent and distribution of axonal dropout in secondary optic atrophy due to IIH. Both optic nerves from a 29-year-old man with a two year history of IIH were examined histologically and morphometrically. A high-contrast lipid (myelin) stain, paraphenylenediamine (PPD), and a semiautomated image analysis system were employed to resolve sufficiently the optic nerve fiber images for counts and for measurement. There were 80% and 90% losses of axons, respectively, in the right and left optic nerves consequent to IIH. The axonal loss in the peripheral area of each optic nerve was much more severe than that in inner sectors (= 0.001 for the right optic nerve and = 0.005 for the left). This pattern of axonal dropout is consistent with the preservation of good central visual acuity despite devastating optic nerve atrophy, and with the severe peripheral visual field loss noted in this patient.

Utilization of the developed digital archives could stimulate the spirit of humanity and creativity, especially for Chinese people in Taiwan, and also satisfy cultural passion and pursuit of knowledge. Furthermore, this study creates simulated informational digital archives of Tainan Chih-Kan-Tower in order to effectively integrate the multiple unique and useful historical records and information. Examples include Chih-Kan- Tower's historical change and Taiwan's ancient map. The study also creates a three dimension (3D) visualization and a two dimension (2D) motion video which, provided by Google Earth, can enhance the experience of media interaction, improve cultural interaction as well as multi-level knowledge by better understanding . With further research on application of digital archives in multiple facets, the finally developed digital archives have great potential to become a very useful tool to promote the most valuable cultural heritage in the nation.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infection is becoming a critical problem worldwide. Currently, only limited therapeutic options are available for the treatment of infections caused by MDR P. aeruginosa, therefore, the development of new alternative treatments is needed. Toluidine blue O (TBO) is an effective antibacterial photosensitizing agent against various bacteria. However, reports on antibacterial photosensitization of MDR bacteria are limited. This study aims to determine the in vitro photobactericidal activity of TBO against MDR P. aeruginosa.The efficacy of antibacterial photodynamic inactivation, DNA fragmentation and protein carbonylation of three MDR P. aeruginosa strains and one susceptible strain was compared using TBO as the photosensitizer followed by red light irradiation (630 nm, 90 J/cm(2)) from a light-emitting diode light source. Subsequently, the efficacy of TBO photodynamic inactivation (TBO-PDI) on 60 MDR strains, including 11 with the efflux pump phenotype and 49 with no pump activity, was tested using the minimum lethal drug concentration (MLC) assay.TBO-PDI caused similar bactericidal effect (6-7 logs of killing effect), DNA fragmentation and protein carbonylation in three MDR and one susceptible P. aeruginosa strains. Although the TBO accumulation assay indicated that TBO is a substrate for the efflux pump, TBO-PDI produce similar photobactericidal activity against 60 MDR P. aeruginosa strains, either with or without efflux-pump phenotype, and 19 susceptible strains.MDR did not affect the susceptibility of P. aeruginosa strains to TBO-PDI. The efflux pump played an insignificant role in TBO-PDI of MDR P. aeruginosa.

Fluid-fluid levels have commonly been reported to occur in aneurysmal bone cysts but have also been seen in telangiectatic osteosarcoma, chondroblastoma, and giant cell tumor of bone. The authors reviewed their experience with nine bone and three soft-tissue tumors that showed fluid-fluid levels on computed tomographic or magnetic resonance images. The bone tumors included fibrous dysplasia, simple bone cyst, recurrent malignant fibrous histiocytoma of bone, two classical osteosarcomas, and four aneurysmal bone cysts. The soft-tissue tumors included soft-tissue hemangioma and two synovial sarcomas. Except for aneurysmal bone cysts, these types of tumors have not been reported to be associated with fluid-fluid levels. Radiologic-pathologic correlation was available in seven patients; in all seven, the fluid-fluid levels indicated prior hemorrhage. The authors conclude that the presence of fluid-fluid levels in bone or soft-tissue tumors cannot be considered diagnostic of any particular tumor.

Retrospective review of secondary data obtained from the Bureau of National Health Insurance (BNHI) on medical resource utilization in in-patient cervical spinal cord injury patients in Taiwan. Since the start of the National Health Insurance Program in Taiwan in 1995, costs have continued to increase each year. High-level cervical spinal cord injury, a catastrophic illness, consumes a large amount of medical resources. Appropriate control of in-patient costs for these patients is mandatory. Analyses of the factors influencing the health-care costs of these patients are needed, so cost-containment policies can be established by the BNHI to conserve health-care resources. Health-care institutions throughout Taiwan. We obtained secondary data on a randomized basis for diagnostic codes 952.00, 952.01, 952.02, or 952.03 of the International Classification of Diseases, Ninth Revision, Clinical Modification from the BNHI files of annual in-patient expenses during the period from 1998 to 2000. There were 184 hospital admission records studied. The lengths of stay and in-patient costs were significantly different among different hospital types. Length of stay also was statistically different according to patient, gender, and age. The lengths of stay and in-patient costs were influenced by the hospital accreditation level and patient gender. Medical orders were influenced by patient age. Basic and selective diagnostics and therapeutics for high-level spinal cord injury without bone fracture should be established. Thus, patient needs for appropriate medical care will be met and overuse of medical resources will be prevented. Communication among doctors also should be strengthened.

Inspired by rattleback toys, we created small chiral wires that rotate in a preferred direction on a vertically oscillating platform and quantified their motion with experiment and simulation. We demonstrate experimentally that angular momentum of rotation about particle centers of mass is converted to collective angular momentum of center-of-mass motion in a granular gas of these wires, and we introduce a continuum model that explains our observations.

Simultaneous time-resolved measurements of internal structure, granular volume, and boundary shear force are reported for dense granular packing steadily sheared under a fixed normal load. We identify features of the crystallization transition for a deep shear flow, whose height-dependent local mean velocity spans more than five orders of magnitude. This structural change is accompanied by a significant decrease of granular volume and shear force, with a more rapid falloff of particle velocity with depth than occurs in the disordered state. Boundary conditions can have a profound influence on the crystallization of the entire packing. We find that continuously sheared flow can exhibit nonunique final states even under identical boundary conditions; a few cycles of oscillatory pretreatment can initiate states that evolve into either a crystallized or a disordered final state after long-term unidirectional shearing. On the other hand, the disordered state can be stabilized after being sufficiently compacted by unidirectional shear. These experiments raise interesting questions about how prior history is recorded in the internal structure of granular packings, affecting their instantaneous rheology and long-term evolution in response to shear.

Internal imaging using index matching, and sensitive volume measurement, are used to investigate the spatial order and dynamics of a deep disordered layer of spheres sheared under a fixed load. Shearing triggers a crystallization transition accompanied by a step compaction event. The delay preceding the transition depends strongly on the layer thickness and can require a translation of about ${10}^{5}$ particle diameters. The mean velocity varies with depth by more than five decades, and its profile is qualitatively altered by the transition.

A general procedure for structure-level adaptation for multilayer feedforward networks is proposed. The general concept of structure-level adaptation for artificial neural networks is presented, and the algorithm for feedforward networks is introduced. The operation of the algorithm is demonstrated by computer simulation on a simple classification problem with time-varying statistics. The results confirm that the algorithm can find the correct structural representation for multilayer feedforward neural networks in time-varying environments. The addition of structure-level adaption to parameter adaptation provides an artificial neural network system with more complete adaptation power than a system that allows only parameter adjustments. >

To succinctly update information on the pathogenesis, etiology, diagnosis, and treatment of neovascular glaucoma based on a systematic review of available literature and to provide summary recommendations rated for their importance to clinical outcome.Neovascular glaucoma is a devastating ocular disease that often results in loss of vision. The current standard of care includes retinal ablation and control of increased intraocular pressure with medical and surgical therapy. LITERATURE REVIEW METHODOLOGY: The authors conducted a MEDLINE literature search of articles published in English from 1966 to the present. Each article reviewed was rated as to the strength of evidence it provided, and summary ratings for the strength of evidence supporting clinical recommendations were generated.Level A (most important to patient outcome) recommendations for the diagnosis of neovascular glaucoma include a high index of suspicion, a full ocular examination including undilated gonioscopy, and pupil examination. In regard to treatment, Level A recommendations include treatment of the underlying disease origin, complete panretinal photocoagulation (if retinal ischemia is a factor), and medical control of both elevated intraocular pressure and inflammation. Level B recommendations (moderately important to patient outcome) encompass glaucoma surgery to control intraocular pressure when medical therapy is unsuccessful, although the ideal surgical procedure is unknown. Currently, trabeculectomy with antimetabolite therapy, aqueous shunt implants, and diode laser cyclophotocoagulation are the preferred surgical treatment options.The current literature on neovascular glaucoma has few articles that provide strong evidence in support of therapy recommendations (level I). Future research studies are needed to address areas in which the current evidence is moderately strong (level II) or weak, consisting only of a consensus of expert opinion (level III). Whenever practicable, these studies should be prospective, randomized clinical trials.

We encountered two hemodialysis (HD) patients with recurrent infections and complete immunoglobulin A deficiency (IgAD). To survey the possibility of a similar occurrence in other populations, we conducted the present study. We used nephelometry to examine the levels of immunoglobulins G (IgG), A (IgA), and M (IgM) in 42 continuous ambulatory peritoneal dialysis (CAPD) patients, 246 HD patients, 56 chronic renal failure (CRF) patients, and 250 normal adults. Four CAPD patients (9.5%) and five HD patients (2.0%) were found to be completely IgA deficient (IgA6.67 mg/dL). Peritoneal dialysis patients therefore had a significantly higher prevalence of IgAD compared with HD and CRF patients. The underlying diseases leading to dialysis therapy in the IgAD patients varied. Their dialysis durations also varied. The occurrence rate of peritonitis in CAPD patients with IgAD was no higher than in patients without IgAD. The clinical significance of IgAD was focused on mucosal immunity, but the exact prevalence of infection was difficult to define. However, these patients' medical records did suggest more frequent respiratory tract infections and cellulitis events than did the records of patients without IgAD. Two PD patients with IgAD died of pneumonia. Immunodiffusion and indirect ELISA methods were used to detect the presence of auto-antibodies, successfully identifying them in three patients. Further research is needed to study other mechanisms of IgAD.

Egr-1 is a transcription factor that couples short-term changes in the extracellular milieu to long-term changes in gene expression. In cultured endothelial cells, the Egr-1 gene has been shown to respond to a variety of extracellular signals. However, the physiological relevance of these findings remains unclear. To address this question, the growth factor-mediated response of the Egr-1 gene under in vivo conditions was analyzed. To that end, either vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) was injected into the intraperitoneal cavity of mice. Growth factors were delivered to all tissues examined, as evidenced by the widespread distribution of I(125)-labeled growth factors and the phosphorylation of their respective receptors. In Western blot analyses of whole-tissue extracts, Egr-1 protein levels were shown to be induced in the heart, brain, liver, and spleen of VEGF-treated mice, and in the heart, lung, brain, liver and skeletal muscle of EGF-treated animals. Changes in Egr-1 levels did not correlate with changes in receptor phosphorylation or ERK1/2 phosphorylation. In Northern blot analyses, VEGF induced Egr-1 mRNA levels in all tissues examined except lung and kidney, whereas EGF led to increased transcripts in all tissues except kidney. In immunofluorescence studies, VEGF induced Egr-1 in microvascular endothelial cells of the heart and liver, and EGF induced Egr-1 in the microvascular bed of skeletal muscle. Taken together, these results suggest that the Egr-1 gene is differentially regulated in response to systemically administered VEGF and EGF. (Blood. 2000;96:1772-1781)

The purpose of this study was to investigate the roles of the second thoracic sympathetic segment in the sympathetic innervation of the hands and face, and to compare skin temperature changes in the palms, fingers, face, and neck of palmar hyperhidrosis (PH) patients before and after endoscopic thoracic sympathectomy.Twenty-two patients, 14 women and eight men, with severe PH were treated with endoscopic ablation of the T2 segment. The skin temperatures of the hands, neck, and face were assessed by infrared thermography both before and after operation.All obtained satisfactory relief of PH. Before sympathectomy, thermography revealed that the palmar skin temperature (PST) was significantly lower than the facial temperature by 1.3 degrees C (paired t-test, p0.005). After sympathectomy, thermography showed significant elevations in temperature mainly of the thenars, palms, digits, and nose, but not of the forehead, mandible, or neck (ANOVA, p0.05 with Bonferroni t-test). The variations in PST among PH patients were much greater preoperatively than postoperatively. More prominent postoperative PST elevation was found in PH patients with lower preoperative PST (r = 0.898, p0.001).These findings demonstrate that the T2 segment is the key source of sympathetic innervation to the hand and that the T2 segment contributes only trivial sympathetic innervation to the face. The results of the present thermography studies offer descriptive information about the autonomic innervation of the upper thoracic sympathetic trunk.

To determine whether the 24-2 Humphrey visual field (HVF) (Humphrey, San Leandro, CA) strategy provides information comparable to that provided by the 30-2 strategy in patients with optic nerve disease.In part A of the study, an occluder device was designed to cover the additional outer 22 points tested in the 30-2 strategy of 187 HVFs from neuro-ophthalmology patients with nonglaucomatous optic neuropathy and 206 HVFs from patients with glaucoma. This device converted the gray scale and probability plots of the 30-2 HVF to a 24-2 field. Fields were initially read using the occluder and then were read in a masked manner without the occluder and compared. In part B, 15 healthy volunteers performed both 30-2 and 24-2 HVFs. Testing time and global indices were compared. Ninety-five percent of the fields in the neuro-ophthalmology patients, 96% of the fields in patients under observation for suspected glaucoma, 98% of the fields in patients with ocular hypertension, and 100% of the fields in patients with glaucoma were read similarly with the 24-2 and 30-2 strategies. In the few cases in which a discrepancy was noted between the 24-2 and the 30-2 fields, appropriate clinical management would not have been compromised by using the 24-2 strategy. Most of these cases were in patients with idiopathic intracranial hypertension and very subtle nerve fiber bundle defects. The 24-2 strategy had a significantly lower pattern standard deviation (P0.01) and corrected pattern standard deviation (P = 0.05) than did the 30-2 strategy. In addition, the 24-2 strategy shortened the standard threshold testing time by 28% in normal volunteers (P0.0001 ).In most cases, the 24-2 testing strategy provides information comparable to that provided by the 30-2 strategy in a shorter time and with less variability. A 30-2 HVF may be warranted in patients under observation for evolving idiopathic intracranial hypertension.

The purpose of this study was to compare the differential susceptibility to photodynamic therapy (PDT) mediated damage in human U-105MG glioma cells and CH-157MN meningioma cells in vitro using 5-amino-levulinic acid (ALA) as photosensitizer, and to determine if growth factors would enhance PDT-mediated damage of these cells.U-105MG or CH-157MN cells were irradiated with polychromatic light in the presence of ALA. A Xenon lamp (150 W) was used as the light source. For the study on the effect of growth factor on ALA-PDT, cells were cultured in serum free medium for 24 hours. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet derived growth factor BB (PDGF-BB) was added to achieve a final concentration of 50 ng/ml. 30 minutes later, cells were incubated with ALA (100 microg/ml) for 24 hours, washed, and irradiated with light (11 J/cm2). MTT tetrazolium assays were performed 24 hours after light irradiation.The inhibition of metabolic cellular function in U-105MG cells by ALA depended on both light energy density and ALA concentration. The susceptibility to ALA-PDT was profoundly lower for CH-157MN meningioma cells than U-105MG glioma cells. When incubated with ALA (100 microg/ml), U-105MG cells exhibited an LD50 around 8 J/cm2 of light irradiation, whereas that of CH-157MN cells was more than 25 J/cm2. EGF, bFGF, or PDGF-BB did not have any effects on the susceptibility of these two cell lines to ALA-PDT.ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells. The differential susceptibility was likely due to differential accumulation of PpIX in these cells. EGF, bFGF, or PDGF-BB did not have stimulatory or inhibitory effect on the efficiency of ALA-PDT.

Previously, we induced vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) secretion in glioma cell lines by using physiologic concentrations of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), or platelet-derived growth factor-BB (PDGF-BB). We hypothesized that VEGF/VPF might enhance the blood supply required for the unregulated growth of tumors, and that it acts as the central mediator of tumor angiogenesis. The objective of this study was to determine whether the expression of VEGF/VPF by meningiomas is regulated by growth factors or sex hormones. By means of an enzyme-linked immunosorbent assay of CH-157MN meningioma cell supernatants, we demonstrated that EGF and bFGF similarly induce VEGF secretion by CH-157MN meningioma cells. At the maximum concentrations of EGF (50 ng/mL) and bFGF (50 ng/mL) used in this study, VEGF secretion was induced to 140% to 160% above baseline constitutive secretion. PDGF-BB homodimer did not enhance VEGF secretion significantly. Estradiol (up to 10(-7) mol/L), progesterone (up to 10(-5) mol/L), or testosterone (up to 10(-5) mol/L) did not stimulate or inhibit VEGF secretion in CH-157MN meningioma cells (p0.05). Furthermore, we demonstrated that dexamethasone decreased VEGF secretion to 32% of baseline constitutive secretion. This might explain the effect of corticosteroids in alleviating peritumoral brain edema in meningiomas. These results suggest that VEGF secretion in CH-157MN meningioma cells is mainly regulated by growth factors and corticosteroids, but not by sex hormones. Understanding the regulation of VEGF/VPF secretion in meningiomas might contribute to the development of a new therapeutic strategy.

To determine the efficacy of surgical revision of glaucoma shunt implants in patients with advanced glaucoma.The records of 13 patients who underwent revision of their shunt implants were retrospectively reviewed.Surgical success was achieved in: 3 of 3 patients (100%) with drainage tube malposition or extrusion; 1 of 6 patients (17%) with occlusion of the intracameral portion of the drainage tube; and 1 of 4 patients (25%) with elevated intraocular pressure secondary to fibrous capsule formation over the implant.Surgical revision of glaucoma shunt implants is a useful procedure in patients who develop tube malposition or extrusion. Surgical revision is much less effective in patients with tube occlusion or fibrous capsule formation. Failure of the shunts due to recurrent fibrosis is commonly observed.

Severe hypophosphatemia is a potentially life-threatening medical condition and might lead to a fatal outcome in critically ill patients. The situation is further complicated by the co-morbid renal failure. We evaluated the efficacy and safety of the intravenous phosphate repletion in 15 renal failure patients with severe hypophosphatemia. Six patients with advanced renal failure and nine patients under maintenance hemodialysis, 7 males and 8 females, aged between 42 and 83 years old, were found to have serum phosphate level1.2 mg/dL from various medical conditions and were treated with intravenous phosphate infusion. The phosphate solution prepared from sodium dihydrogen phosphate (NaH2PO4), containing 13 mg/ml phosphate and 0.5 meq/ml sodium, in the dosage 2.5-3.0 mg phosphate/Kg body weight, was administered through the central venous lins every 6-8 hours. The infusion was discontinued once serum phosphate level reached 5.0-5.5 mg/dL. Serum ionized calcium, phosphate and intact parathyroid hormone levels were serially followed at different intervals, respectively. The hemodialyzed uremic patients received their dialysis treatment as scheduled. All patients survived the hypophosphatemic period and regained normal phosphate levels after repletion. The amount of phosphate administered to reach the target level ranged between 3438 and 9150 mg and the duration of treatment varied between six and seventeen days. Hypocalcemia (4.2 mg/dL) was noted at eight occasions during the whole treatment period but none was symptomatic. Eleven patients recovered from the offending illness. However, four patients expired due to reasons not directly consequent to and temporally remote from hypophosphatemia. We conclude that prompt repletion of severe hypophosphatemia and phosphate deficiency with relatively slower rate of NaH2PO4 solution intravenous infusion is a safe and effective mode of treatment for renal failure and uremic patients. The longer treatment period allowed the administered minerals full equilibration. The risk of hyperkalemia is avoided and the sodium/volume load can be eliminated by dialysis.

To analyze the results of intraocular pressure (IOP) reduction by diode laser contact cyclophotocoagulation ("cyclodiode") in cases of advanced glaucoma refractory to alternative treatments.Two hundred and ten eyes of 195 patients, ages 1 to 89 years (mean, 51 years) were followed for 3 to 30 months (mean, 10 months) after cyclodiode treatment.More than one treatment was given in 102 eyes (49%), and the overall mean number of treatments given per eye was 1.75 (range, 2-5). Mean pretreatment IOP was 34.1 mmHg (+/-10.6 mmHg). At last follow-up, mean IOP was 20.1 mmHg (+/-9.3 mmHg), and mean total medications was reduced from 2.3 to 1.7. Mean final IOP was lowest in patients with silicone oil glaucoma (17.3 mmHg), and the mean reduction in IOP was greatest in patients with neovascular glaucoma (23.9 mmHg). At last follow-up, visual acuity was worse than before treatment in 29% of eyes, unchanged in 60%, and better in 11%. Overall success rate (IOP22 mmHg) was 66% at a mean follow-up of 10 months. Phthisis occurred in one eye (0.5%), and chronic hypotony (0 mmHgIOP5 mmHg for3 months) in a further two eyes (1%). Corneal graft decompensation followed treatment in two eyes, macular pucker occurred in one eye, and combined hyphema/vitreous hemorrhage in one patient.Diode laser cycloablation is relatively safe and effective at controlling IOP in eyes with advanced refractory glaucoma in the short and medium term. With the treatment parameters used, multiple applications may be needed.

Patients who use PermCath as the vascular access for long-term hemodialysis are occasionally confronted with catheter-related infections. Recently, we have treated 17 patients suffering from PermCath-related sepsis. The clinical presenting features were leukocytosis in 14/17, high fever and shaking chill during dialysis in 12/17, and signs of exit site infection in 3/17. No shock was found. All patients received clinical evaluation to exclude infection sources other than from blood and inside the catheter, such as pulmonary, genitourinary, hepatobiliary and cutaneous systems. Blood drawn from both PermCath and peripheral vein was sent for bacterial culture. Bacterial culture of the blood samples from PermCath revealed Staphylococcus sp. in 7/17, Pseudomonas sp. in 5/17, Enterobacter sp. in 4/17, Streptococcus sp. in 1/17. Fourteen blood samples from peripheral vein showed positive culture results identical to those from PermCath, but negative study were noted in three other patients. The patients were divided into two treatment groups: Group I: systemic antibiotics without PermCath removal in 7, Group II: "locked-in" retention in addition to systemic anti-biotics in 10. Antibiotics were empirically chosen according to bacteriological studies. In the "locked-in" retention treatment, antibiotics were retained into both the inflow and outflow PermCath lumens in the exact volume of each lumen for 24 hours. The antibiotics solutions were replaced on a daily basis. The same antibiotics were also given intravenously. Duration of treatment depended on clinical progression and follow-up blood culture results and ranged between 13 and 24 days. The schedule of dialysis was not changed through the period of PermCath-related sepsis. The sepsis was cured in all group II cases but not in 2 of group I and resulted in mortality in these 2 patients. The PermCaths were preserved in 5/7 in group I with two mortality cases and all except one preserved in group II patients without mortality. We suggested that "locked-in" retention in addition to systemic antibiotics is the treatment of choice for the patients with PermCath-related sepsis. This method also preserves the functional integrity of PermCath, which is the lifeline vascular access of the patients with exhausted native vessels.

The combination of N-(phosphonacetyl)-L-aspartate (PALA), 6-methylmercaptopurine riboside (MMPR), and 6-aminonicotinamide (6AN) has been shown to be an effective antineoplastic regimen and also to enhance the effects of other antineoplastic agents (1-4). To further enhance the effect of this combination, we investigated the effects of adding adriamycin, at its maximally tolerated dose, to this regimen. The response rate (complete regression+partial regression) for the four-drug regimen was higher than for the three-drug regimen, and the tumor growth delay was also significantly higher than for treatment with PALA, MMPR, 6AN, or after treatment with maximally tolerated doses of adriamycin alone (11 mg/kg). The addition of adriamycin to PALA, MMPR, 6AN did not result in enhancement of the effect of radiation, as measured by tumor growth delay studies and tumor control (complete and partial regression rate). The mechanism of action of the combination of PALA, MMPR, and 6AN is not known definitively, but a possible mechanism previously suggested is biochemical modulation of energy metabolism and inhibition of production of tumor ATP. Treatment with PALA, MMPR, 6AN, and adriamycin (at 2.5 hr post MMPR, 6AN) resulted in a nadir NTP/Pi value, as determined by 31P NMR spectroscopy, at approximately 10 hr post MMPR + 6AN (7.5 hr post adriamycin), which was not significantly different from the NTP/Pi value determined after treatment with the three-drug combination.

A mirror needle holder has been designed to facilitate the passage of a needle through the ciliary sulcus during transscleral fixation of posterior chamber (PC) intraocular lens (IOLs). Two human postmortem eyes were used to demonstrate the efficacy of this mirror used as the needle holder. This method was compared with the current method of passing sutures without view of the ciliary sulcus. The mirror needle holder demonstrated precise passage of the needle into the ciliary sulcus by direct visualization of the ciliary processes and sulcus. This method may avoid the complications associated with transsclerally sutured PC IOLs during penetrating keratoplasty and secondary IOL placement.

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.

Objective Patients with chronic kidney disease (CKD) have more cognitive impairments. However, the etiologies are not fully clear. Plasma homocysteine levels and vascular burden rise in CKD; meanwhile, high homocysteine levels and vascular factors are known risk factors of dementia in non-CKD patients. Thus, we aimed to investigate the association between homocysteine, vascular burden and cognitive impairment in CKD and to see if the effect of elevated homocysteine on cognitive impairment mediated by vascular factor. Methods 146 patients with CKD and 69 normal comparisons were recruited. Cognitive function was evaluated by comprehensive neuropsychological tests assessing processing speed, executive function, language, visuospatial function, memory, and attention domains. Vascular burden was assessed by Framinghan cardiovascular risk scale (FCRS) which indicates risk of atherosclerotic diseases including stroke. Results In controlled analysis, patients with CKD had lower scores in all cognitive domains, and had higher homocysteine levels (18.5±6.4 vs. 9.8±2.9, p Conclusion Patients with CKD had extensive cognitive impairments. Elevated homocysteine levels may be an risk factor, which is independent of vascular burden, of cognitive impairment on processing speed and executive function. Further studies to investigate if normalization of homocysteine can improve cognitive function will be suggested.

The long-term efficacy and safety of filtering surgery with 5-fluorouracil (5-FU) in eyes with neovascular glaucoma are unknown.Kaplan-Meier survival curve analysis of surgical outcome was performed on all 34 patients (34 eyes) enrolled from May 1982 through April 1986 in the original pilot study of filtering surgery with 5-FU.Success rates at the 1-, 2-, 3-, 4-, and 5-year intervals were 71%, 67%, 61%, 41%, and 28%, respectively. The median filter survival time was 38.7 months (95% confidence interval: 32-45 months). Twelve (35%) of 34 patients lost light perception vision, and phthisis bulbi developed in 8 (24%) of 34 patients. Age of 50 years or younger (P0.0001) and type 1 diabetes (P = 0.0004) were significant risk factors for surgical failure. The 1-year success rate for patients no older than 50 years of age was 23% compared with a 95% success rate in patients older than 50 years of age. After adjustment for age, type 1 diabetes was a borderline risk factor (P = 0.06).There is a high risk of long-term failure of filtering surgery with 5-FU in neovascular glaucoma. Patients 50 years of age or younger have an extremely poor prognosis. Patients older than 50 years of age have initial short-term success with an accelerated failure rate after 3 years.

Endothelin-1 (ET-1) is a powerful vasoconstrictor, primarily secreted by vascular endothelial cells. It may be an important mediator for radiocontrast-induced renal vasoconstriction, which may cause acute renal failure in susceptible subjects. This study measured the release of ET-1 by cultured porcine endothelial cells under incubation with various radiocontrast agents. Compared with the control group, the conventional ionic radiocontrast, diatrizoate, induced a dose- and time-dependent increase in ET-1 release. The lowest concentration of diatrizoate required to induce an increase in ET-1 secretion was 1 mM, less than the estimated serum level (about 5.2 mM) in clinical radiographic practice, suggesting that a direct release of ET-1 from endothelial cells may take place in clinical image studies. The stimulation effect of the following contrast agents on endothelial ET-1 release was compared: diatrizoate (ionic monomer), ioxaglate (ionic dimer), iohexol (nonionic monomer), iotrolan (nonionic dimer). Higher levels of ET-1 release were stimulated by ionic agents compared to the nonionic agents, but no difference in the degree of stimulation was observed between the monomeric and dimeric forms. All agents significantly increased ET-1 release compared with the control group. ET-1 production stimulated by radiocontrast agents was independent of hyperosmolality and was primarily seen as an increase in ET-1 mRNA. The increase in ET-1 release was actinomycin D-sensitive, and ET-1 mRNA abundance was greatly enhanced by cycloheximide. The augmented ET-1 mRNA expression to radiocontrast treatment was not secondary to the enhanced message stability. The data suggest that the contrast media-induced increments in ET-1 release are transcription-dependent and that both ionic and nonionic radiocontrast agents have a renal vasoconstrictive effect that is mediated by ET-1 and may potentially be nephrotoxic in susceptible subjects. Nonionic agents may be less toxic.

We utilize real-time single-molecule imaging to investigate the transient response of DNA molecules on a rigidly supported lipid membrane upon their adsorptions. Following the stochastic landing onto the membrane at a nearly spherical initial state, these DNA coils gradually relax and expand their apparent size (R2g,xy) in a highly anisotropic fashion. The evolution of R2g,xy exhibits considerable variations among individual molecules, and its time dependence can be characterized by a generic exponential relaxation, but only after a statistical averaging over a large number of events. This evolution defines the primary relaxation timescale, which varies with the lipid composition of the membrane. The statistics and time-resolved analyses of the conformation of individual DNA coils further indicate that the interaction between the absorbing molecules and the lipid elements plays an important role in the relaxation towards the final equilibrium of this polymer-membrane complex.