Evaluación de la percepción de las barreras en la asistencia sanitaria y del impacto de las inyecciones intravítreas en la degeneración macular asociada a la edad neovascular / AEvaluación de la percepción de las barreras en la asistencia sanitaria y del impacto de las inyecciones intravítreas en la degeneración macular asociada a la edad neovascular

Propósito Evaluar la percepción de las barreras en la asistencia sanitaria y del impacto de las inyecciones intravítreas en los pacientes con degeneración macular asociada a la edad neovascular (DMAEn). Métodos Estudio transversal de 108 pacientes con DMAEn en tratamiento con inyecciones intravítreas mediante un cuestionario de 26 preguntas (puntuación del 1 al 5) divididas en 3 bloques: 1)enfermedad y su tratamiento con inyecciones; 2)barreras en la asistencia sanitaria, y 3)nuevas tecnologías. Resultados La edad media fue 80,4±7,0 años y la agudeza visual (AV) de 75,2±12,4 letras. Las principales barreras en la asistencia sanitaria fueron los largos tiempos de espera en consulta (72%), seguida por otras comorbilidades (10%). El 63% de los pacientes dedican entre 3 y 5h para acudir a la consulta. Se apreció una ansiedad notable debida a las inyecciones (2,8±1,3), estando presente en el 71% el día antes. Se observó un gran miedo a la ceguera y a dejar de ser independientes (4,4±0,9 y 4,3±1,1), sin existir diferencias en relación con la AV, la edad o el sexo (p≥0,135). El 28% de los pacientes refieren que les cuesta bastante o mucho la asistencia a consulta, presentando el 69% del total un gran interés en tener un aparato diagnóstico en el domicilio. Conclusiones La DMAEn y su tratamiento suponen una importante carga asistencial para los pacientes, existiendo un gran miedo a la ceguera y a perder su independencia, siendo la principal barrera el largo tiempo de espera en consulta (AU)

Aim To evaluate the perception of barriers in healthcare and the impact of intravitreal injections in patients with neovascular age-related macular degeneration (nAMD). Methods Cross-sectional study including 108 patients with nAMD in treatment with intravitreal injections. The patients answered a questionnaire with 26 questions (score from 1 to 5) divided in three sections: 1)the disease and its treatment with injections; 2)healthcare barriers, and 3)new technologies. Result The mean age was 80.4±7.0 years and visual acuity (VA) was 75.2±12.4 letters. The main barriers in healthcare were long waiting times (72%), followed by other comorbidities (10%). Some 63% of patients have to wait between 3 and 5hours to attend their clinical visit. Significant anxiety due to the injections (2.8±1.3) was observed, being present in 71% of the cases the day before. A great fear of blindness and losing independence was observed (4.4±0.9 and 4.3±1.1), with no differences in relation to VA, age or sex (P≥.135). Moreover, 28% of the patients reported that it was quite or very difficult for them to attend the clinical visit, with 69% of the total showing great interest in having a diagnostic device at home.Conclusion The nAMD and its treatment represent a significant burden on patients, among whom there is a great fear of blindness and of losing their independence, the main barrier being the long waiting time for the clinical visit (AU)

Calretinin-immunoreactive unipolar brush cells in the developing human cerebellum.

We have studied the temporal and spatial characteristics of the development of unipolar brush cells (UBCs) in the human cerebellar vermis. Consistently with previous studies in rodents and cat, we have found that unipolar brush cells appear at a relatively late phase of cerebellar development and their development continues up to and beyond the first postnatal year. A series of 23 normal human brains, including 5 adult and 18 fetal or infant brains (between the 24th gestational week and the 11th postnatal month) were used. In order to visualize unipolar brush cells, calretinin-immunocytochemistry was performed on formaldehyde-fixed, paraffin-embedded blocks of the cerebellar vermis. Our results show that calretinin-immunoreactive unipolar brush cells are not yet present in the cerebellar vermis at the 28th gestational week. At birth, they are present in a relatively small number, mostly in the vestibular lobules. At the 3rd, 5th, 8.5th and 11th postnatal months the number of calretinin-immunoreactive unipolar brush cells gradually increase, first appearing in the vestibular lobules, followed by the invasion of the later developing vermal lobules, spreading in a rostro-caudal and proximo-distal direction. Although at the 11th postnatal month unipolar brush cells exhibited adult-like morphological and distributional features, their number appeared to be lower than in the adult cerebellum. The late maturation of unipolar brush cells implies that the cytoarchitectonical development of the human cerebellum is not completed by the end of the first postnatal year.

Delayed postnatal settlement of cerebellar Purkinje cells in vermal lobules VI and VII of the mouse.

The postnatal development of the ganglionic (Purkinje) layer was studied in the mouse cerebellum from P0 to young adulthood with special emphasis to vermal lobules VI-VII (oculomotor vermis) in the mouse. In order to visualize Purkinje cells (PCs), toluidine blue staining of resin-embedded semithin sections and calbindin immunohistochemistry were utilized. The number of PCs in the whole cerebellum was 199,080+/-2966 at postnatal day eight (P8), 222,000+/-2979 at P20 and nearly the same, 225,800+/-7549 in young adults; i.e., there was an approximately 13.4% increase of PCs between P8 and adults. The number of PC somata aligned into a rostrocaudal stripe along the developing ganglionic layer increased by about 24% in vermal cerebellar lobule III but much more markedly (i.e., by 49%) in VI+VII between P6 and young adulthood. Between P6 and P16, the increase of the number of PCs in the ganglionic layer of lobules VI and VII resulted in the (delayed) completion of PC layer, caused by the (late) alignment of rostrocaudally dispersed PCs, although late postnatal migration of a smaller population of these cells cannot be excluded either. It is concluded that the oculomotor vermis belongs to the latest developing cerebellar cortical structures, which could be the reason for its frequent involvement in developmentally related disturbances and disorders.

Quantitative analysis of the postnatal development of Purkinje neurons in the cerebellum of the cat.

We have studied the postnatal quantitative changes of cortical Purkinje neurons in the cerebellum of the cat at the following postnatal groups of age: P0, P42, P72 and adults. An unbiased counting method, the optical fractionator was used for the estimation of Purkinje cell numbers. A significant increase of Purkinje cell number was found between P0 (1.097 x 10(6)) and P42/P72 (1.805 x 10(6) and 1.895 x 10(6)) declining to 1.429 x 10(6) in the adult, still 30% higher than in the newborn. It was also observed that during the first few postnatal weeks large "gaps" were present in the Purkinje monolayer as revealed by Nissl staining and metabotropic glutamate receptor 1alpha immunocytochemistry. These Purkinje cell gaps were observed most frequently in well-definable areas, especially in the intermediate zone of the neocerebellum. Simultaneously with the numerical increase of Purkinje neurons between the P0 and P72 age groups, these gaps disappeared after the third postnatal week resulting in the completion of the Purkinje monolayer in the whole cerebellum.

Compartmentation of the reeler cerebellum: segregation and overlap of spinocerebellar and secondary vestibulocerebellar fibers and their target cells.

The cerebellum of the reeler mutant mouse has an abnormal organization; its single lobule is composed of a severely hypogranular cortex and a central cerebellar mass (CCM) consisting of Purkinje cell clusters intermixing with the cerebellar nuclei. As such the reeler represents an excellent model in which to examine the effect of the abnormal distribution of cerebellar cells on afferent-target relationships. To this effect we studied the organization of the spinocerebellar and secondary vestibulocerebellar afferent projections in homozygous reeler mice (rl/rl) using anterograde tracing techniques. Spinal cord injections resulted in labeled spinocerebellar mossy fiber rosettes in specific anterior and posterior regions of the cerebellar cortex. Some vestiges of parasagittal organization may be present in the anterior projection area. Within the CCM, labeled fibers appeared to terminate on distinct groups of Purkinje cells. Thus, the spinocerebellar mossy fibers seem to form both normal and heterologous synapses in the reeler cerebellum. Secondary vestibular injections resulted in both retrograde and anterograde labeling. Retrograde labeling was seen in clusters of Purkinje cells and cerebellar nuclear cells; anterograde labeling was distributed in the white matter and in specific regions of the anterior and posterior cortex of the cerebellum. The labeled spinocerebellar and secondary vestibulocerebellar afferents overlapped in the anterior region but in the posterior region the vestibulocerebellar termination area was ventral to the spinocerebellar area. An area devoid of labeled terminals was also observed ventral to the posterior secondary vestibulocerebellar termination field. Using calretinin immunostaining it was determined that this area contains unipolar brush cells, a cell type found primarily in the vestibulocerebellum of normal mice. Our data indicate that despite of the lack of known landmarks (fissures, lobules) the spinocerebellar and vestibulocerebellar afferent projections in the reeler cerebellum do not distribute randomly but have specific target regions, and the position of these regions, relative to each other, appears to be conserved. Two caveats to this were the finding of overlapping terminal fields of these afferents in the anterior region, and a posteroventral region that contains unipolar brush cells yet is devoid of secondary vestibulocerebellar afferents. The distribution of Purkinje cells and cerebellar nuclear cells is not random either; those that give rise to cerebellovestibular efferents form distinct groups within the central cerebellar mass.

Postnatal development of unipolar brush cells in the cerebellar cortex of cat.

The postnatal developmental distribution pattern of metabotropic glutamate receptor (mGluR1a) immunoreactive unipolar brush cells (UBCs) was studied in the cerebellar cortex of kittens. On the day of birth (P0) UBCs are already present in the white matter in lobule X of the vermis, but only a few of these cell seemed to migrate to the deeper region of the internal granular layer. By the end of the first week (P8) UBCs were seen to invade the white matter + internal granular layer of lobules IX, VIII, I, and II of the vermis, and they spread further in the transitory area medio-laterally from the vermis toward the cerebellar hemispheres. By P15, UBCs appeared in lobules III and VII of the vermis, as well as in corresponding lobules of the neocerebellum, with especially high numbers in lobule VII. By P22, UBCs migrated further after their medio-lateral course in the neocerebellum, and began to invade lobules V and VI. At P62 the amount of UBCs in midsagittal planes of early developing vermal lobules (I, II, VII-X) resembled the P132 or adult pattern. The medio-lateral migration and incorporation of UBCs into the late-developing cerebellar lobules V and VI was completed only by P132, when the spatial distribution of UBCs in both the vermal and neocerebellar lobules was comparable to that seen in the 1 year old young adult cat. Although by P132 the postnatal migration of the vast majority of UBCs seemed to be completed, in the cerebellum of adult cats a few migrating UBCs could still be observed in the white matter of the cerebellar lobules, and beneath the ependyma of the fourth ventricle. It is concluded that during ontogenesis the migration course of UBCs follows essentially the developmental sequence of cerebellar lobules, although the incorporation of UBCs into the internal granular layer continues until 4 months postnatally, i.e., much beyond the apparent completion (about two months postnatally) of cytoarchitectonic built up of the cerebellar cortex of kittens.

Noise in microelectromechanical system resonators.

Microelectromechanical system (MEMS) and nanoelectromechanical system (NEMS) based resonators and filters, ranging in frequencies from kHz to GHz, have been proposed. The question of how the stabilities of such resonators scale with dimensions is examined in this paper, with emphasis on the noise characteristics. When the dimensions of a resonator become small, instabilities that are negligible in macro-scale devices become prominent. The effects of fluctuations in temperature, adsorbing/desorbing molecules, outgassing, Brownian motion, Johnson noise, drive power and self-heating, and random vibration are explored. When the device is small, the effects of fluctuations in the numbers of photons, phonons, electrons and adsorbed molecules can all affect the noise characteristics. For all but the random vibration-induced noise, reducing the dimensions increases the noise. At submicron dimensions, especially, the frequency noise due to temperature fluctuations, Johnson noise, and adsorption/desorption are likely to limit the applications of ultra-small resonators.

Comments on the effects of nonuniform mass loading on a quartz crystal microbalance.

The Sauerbrey equation can yield incorrect results when the mass and amplitude of vibration distributions are not uniform, and when the mass is not attached rigidly.

A temperature insensitive quartz microbalance.

Mass deposition onto a microbalance is generally accompanied by a temperature change. By measuring a single frequency only, it is not possible to separate the frequency change due to mass change from that due to temperature change. In the temperature insensitive microbalance technique, measurements of two frequencies, the fundamental mode and third overtone frequencies of an SC-cut resonator, yield two equations with two unknowns. This allows the separation of mass change effects from temperature change effects. Dual mode excitation can be used for highly accurate resonator self-temperature sensing over wide temperature ranges. SC-cut resonators are also thermal transient compensated. These unique properties allowed the development of a temperature compensated microbalance that is highly sensitive to mass changes, which can be used in rapidly changing thermal environments, over wide temperature ranges, and which requires neither temperature control nor a thermometer other than the resonator. To demonstrate the performance of this microbalance, SC-cut resonators were coated with thin polymethylmethacrylate (PMMA) photoresist films then placed into a UV-ozone cleaning chamber that initially was at about 20 degrees C. When the UV lamp was turned on, the UV-ozone removed PMMA from the surfaces while the chamber temperature rose to about 60 degrees C. The frequency changes due to mass changes could be accurately determined, independently of the frequency changes due to temperature changes.

Long-term aging of oscillators.

The authors report aging results for more than 40 oscillators, from a variety of sources, for periods ranging from 1 yr to more than 10 yr. The aging data were accumulated with an automated aging facility. The oscillators that have been tested include temperature-compensated crystal oscillators (TCXOs) and oven-controlled crystal oscillators (OCXOs). The TCXOs were maintained in a controlled temperature environment. Several of the TCXOs were built for a gun-launched sensor application and have been shown to be capable of surviving more than 30000-g shock levels of 12-ms duration. The aging results for these ruggedized TXCOs are surprisingly good (<2x10(-10)/d). The better OCXOs exhibit long term aging of a few parts in 10(12 )/d.

Military applications of high accuracy frequency standards and clocks.

The application of frequency control and timing devices in modern military electronics systems is reviewed. The manner in which the stability and accuracy of these devices impact the performance of military communication, navigation, surveillance, electronic warfare, missile guidance, and identification-friend-or-foe (IFF) systems is discussed.

Phylogeny of the alpha-crystallin-related heat-shock proteins.

Phylogenetic relationships were examined among 35 alpha-crystallin-related heat-shock proteins from animals, plants, and fungi. Approximately one-third of the aligned amino acids in these proteins were conserved in 74% of the proteins, and three blocks of consensus sequence were identified. Relationships were established by maximum parsimony and distance matrix analyses of the aligned amino acid sequences. The inferred phylogeny trees show the plant proteins clearly divided into three major groups that are unrelated to taxonomy: the chloroplast-localized proteins and two groups that originate from a common ancestral plant protein. The animal proteins, in contrast, branch in accordance with taxonomy, the only clear exception being the alpha-crystallin subgrouping of vertebrates. This analysis indicates that the small heat-shock proteins of animals have diverged more widely than have the plant proteins, one group of which is especially stable.

Hysteresis in quartz resonators-a review.

The literature on the frequency versus temperature characteristics of quartz crystal resonators is reviewed. Three papers that deal with frequency versus pressure hysteresis are included, as these may possibly have relevance to frequency versus temperature hysteresis. It is seen that the causes of hysteresis are not well understood. The evidence to date is inconclusive. The mechanisms that can cause hysteresis include: strain changes changes in the quartz, contamination redistribution, oscillator circuitry hysteresis, and apparent hysteresis due to thermal gradients. The results to date seem to indicate that lattice defects are somehow related to thermal hysteresis. Stress relief in the mounting structure can also produce significant hysteresis. As crystal processing techniques have improved. contamination has become less of a problem.

On acoustic sensor sensitivity.

Acoustic sensor sensitivity expressed as frequency change per unit of measurand can result in the erroneous conclusion that higher-frequency sensors are superior to lower-frequency ones. It is argued that, when compared on the bases of reproducibility and resolution capability, good low-frequency sensors are superior to good high-frequency ones.

Modeling resonator frequency fluctuations induced by adsorbing and desorbing surface molecules.

Resonator frequency fluctuations due to adsorption and desorption of molecules on plate electrodes are studied using the principle of mass-loading effects of adsorbed molecules. The study is based on a 525 MHz, AT-cut quartz resonator enclosed in a small crystal holder. Equations relating the surface adsorption rates of the crystal holder to pressure were derived and found to be quadratic polynomial functions of the adsorption rates. Calculations based on these equations show that a contaminant gas with a higher desorption energy creates larger changes in pressure when the temperature is varied. The function describing the frequency fluctuations due to any one contaminant site is a continuous-time Markov chain. Kolmogorov equations and an autocorrelation function for the Markov chain are derived. The autocorrelation and spectral density function of resonator frequency fluctuations are derived. The spectral density of frequency fluctuations at 1 Hz is studied as a function of pressure, temperature, and desorption energy of molecules. The noise levels for a contaminant gas with one type of molecules are found to be lower for lower desorption energies, and higher at lower pressures.

Resonator surface contamination-a cause of frequency fluctuations?

The mass loading effects of adsorbing and desorbing contaminant molecules on the magnitude and characteristics of frequency fluctuations in a thickness-shear resonator are studied. The study is motivated by the observation that the frequency of a thickness-shear resonator is determined predominantly by such mechanical parameters as the thickness of the resonator, elastic stiffnesses, mass loading of the electrodes, and energy trapping. An equation was derived relating the spectral density of frequency fluctuations to: (1) rates of adsorption and desorption of one species of contaminant molecules; (2) mass per unit area of a monolayer of molecules: (3) frequency constant; (4) thickness of resonator; and (5) number of molecular sites on one resonator surface. The induced phase noises were found to be significant in very-high-frequency resonators and are not simple functions of the percentage of area contaminated. The spectral density of frequency fluctuations was inversely proportional to the fourth power of the thickness if other parameters were held constant.