Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner.

How should initial fit inform soft contact lens prescribing

Purpose: To investigate how initial HEMA and silicone-hydrogel (SiHy) contact lens fit on insertion, which informs prescribing decisions, reflect end of day fit. Methods: Thirty participants (aged 22.9. ±. 4.9 years) were fitted contralaterally with HEMA and SiHy contact lenses. Corneal topography and tear break-up time were assessed pre-lens wear. Centration, lag, post-blink movement during up-gaze and push-up recovery speed were recorded after 5,10,20. min and 8. h of contact lens wear by a digital slit-lamp biomicroscope camera, along with reported comfort. Lens fit metrics were analysed using bespoke software. Results: Comfort and centration were similar with the HEMA and SiHy lenses (p > 0.05), but comfort decreased with time (p <. 0.01) whereas centration remained stable (F = 0.036, p = 0.991). Movement-on-blink and lag were greater with the HEMA than the SiHy lens (p <. 0.01), but movement-on-blink decreased with time after insertion (F = 22.423, p <. 0.001) whereas lag remained stable (F = 1.967, p = 0.129). Push-up recovery speed was similar with the HEMA and the SiHy lens 5-20. min after insertion (p > 0.05), but was slower with SiHy after 8. h wear (p = 0.016). Lens movement on blink and push-up recovery speed was predictive of the movement after 8. h of wear after 10-20. min SiHy wear, but after 5 to 20. min of HEMA lens wear. Conclusions: A HEMA or SiHy contact lens with poor movement on blink/push-up after at least 10. min after insertion should be rejected.

Dissociation of detection and evaluation of facial expressions in adolescence

Holistic face perception, i.e. the mandatory integration of featural information across the face, hasbeen considered to play a key role when recognizing emotional face expressions (e.g., Tanaka et al.,2002). However, despite their early onset holistic processing skills continue to improvethroughout adolescence (e.g., Schwarzer et al., 2010) and therefore might modulate theevaluation of facial expressions. We tested this hypothesis using an attentional blink (AB)paradigm to compare the impact of happy, fearful and neutral faces in adolescents (10–13 years)and adults on subsequently presented neutral target stimuli (animals, plants and objects) in a rapidserial visual presentation stream. Adolescents and adults were found to be equally reliable whenreporting the emotional expression of the face stimuli. However, the detection of emotional butnot neutral faces imposed a significantly stronger AB effect on the detection of the neutral targetsin adults compared to adolescents. In a control experiment we confirmed that adolescents ratedemotional faces lower in terms of valence and arousal than adults. The results suggest a protracteddevelopment of the ability to evaluate facial expressions that might be attributed to the latematuration of holistic processing skills.

Cross sections and Rosenbluth separations from kaon electroproduction on protons up to Q2 = 2.35 (GeV/c)2

The kaon electroproduction reaction H(e, e ′K+)Λ was studied as a function of the four momentum transfer, Q2, for different values of the virtual photon polarization parameter. Electrons and kaons were detected in coincidence in two High Resolution Spectrometers (HRS) at Jefferson Lab. Data were taken at electron beam energies ranging from 3.4006 to 5.7544 GeV. The kaons were identified using combined time of flight information and two Aerogel Čerenkov detectors used for particle identification. For different values of Q2 ranging from 1.90 to 2.35 GeV/c2 the center of mass cross sections for the Λ hyperon were determined for 20 kinematics and the longitudinal, σ L, and transverse, σT, terms were separated using the Rosenbluth separation technique. ^ Comparisons between available models and data have been studied. The comparison supports the t-channel dominance behavior for kaon electroproduction. All models seem to underpredict the transverse cross section. An estimate of the kaon form factor has been explored by determining the sensitivity of the separated cross sections to variations of the kaon EM form factor. From comparison between models and data we can conclude that interpreting the data using the Regge model is quite sensitive to a particular choice for the EM form factors. The data from the E98-108 experiment extends the range of the available kaon electroproduction cross section data to an unexplored region of Q2 where no separations have ever been performed. ^

Contingency, contiguity, and development: The ontogeny of contingency learning in northern bobwhite (Colinus virginianus) chicks

The purpose of this study was to investigate the ontogeny of auditory learning via operant contingency in Northern bobwhite (Colinus virginianus ) hatchlings and possible interaction between attention, orienting and learning during early development. Chicks received individual 5 min training sessions in which they received a playback of a bobwhite maternal call at a single delay following each vocalization they emitted. Playback was either from a single randomly chosen speaker or switched back and forth semi-randomly between two speakers during training. Chicks were tested 24 hrs later in a simultaneous choice test between the familiar and an unfamiliar maternal call. It was found that day-old chicks showed a significant time-specific decrement in auditory learning when trained with delays in the range of 470–910 ms between their vocalizations and call playback only when training involved two speakers. Two-day-old birds showed an even more sustained disruption of learning than day-old chicks, whereas three-day-old chicks showed a pattern of intermittent interference with their learning when trained at such delays. A similar but less severe decrement in auditory learning was found when chicks were provided with motor training in which playback was contingent upon chicks entering and exiting one of two colored squares placed on the floor of the arena. Chicks provided with playback of the call at randomly chosen delays each time they vocalized exhibited large fluctuations in their responsivity to the auditory stimulus as a function of delay—fluctuations which were correlated significantly with measures of chick learning, particularly at two-days-of-age. When playback was limited to a single location chicks no longer showed a time-specific disruption of their learning of the auditory stimulus. Sequential analyses revealed several patterns suggesting that an attentional process similar or analogous to attentional blink may have contributed both to the observed fluctuations in chick responsivity to the auditory stimulus as a function of delay and to the time-specific learning deficit shown by chicks provided with two-speaker training. The study highlights that learning can be substantially modulated by processes of orienting and attention and has a number of important implications for research within cognitive neuroscience, animal behavior and learning.

A search for an exotic meson in the gamma + P decaying to delta++ + pi- + eta reaction

A Partial Waves Analysis (PWA) of γp → Δ ++X → pπ+ π - (η) data taken with the CLAS detector at Jefferson Lab is presented in this work. This reaction is of interest because the Δ++ restricts the isospin of the possible X states, leaving the PWA with a smaller combination of partial waves, making it ideal to look for exotic mesons. It was proposed by Isgur and Paton that photoproduction is a plausible source for the Jpc=1–+ state through flux tube excitation. The π1(1400) is such a state that has been produced with the use of hadron production but it has yet to be seen in photoproduction. A mass independent amplitude analysis of this channel was performed, followed by a mass dependent fit to extract the resonance parameters. The procedure used an event-based maximum likelihood method to maintain all correlations in the kinematics. The intensity and phase motion is mapped out for the contributing signals without requiring assumptions about the underlying processes. The strength of the PWA is in the analysis of the phase motion, which for resonance behavior is well defined. In the data presented, the ηπ– invariant mass spectrum shows contributions from the a0(980) and a2(1320) partial waves. No π1 was observed under a clear a2 signal after the angular distributions of the decay products were analyzed using an amplitude analysis. In addition, this dissertation discusses trends in the data, along with the implemented techniques.

Functional near infrared spectroscopy study of language, joint attention and motor skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Joint-specific changes in locomotor complexity in the absence of muscle atrophy following incomplete spinal cord injury

ackground Following incomplete spinal cord injury (iSCI), descending drive is impaired, possibly leading to a decrease in the complexity of gait. To test the hypothesis that iSCI impairs gait coordination and decreases locomotor complexity, we collected 3D joint angle kinematics and muscle parameters of rats with a sham or an incomplete spinal cord injury. Methods 12 adult, female, Long-Evans rats, 6 sham and 6 mild-moderate T8 iSCI, were tested 4 weeks following injury. The Basso Beattie Bresnahan locomotor score was used to verify injury severity. Animals had reflective markers placed on the bony prominences of their limb joints and were filmed in 3D while walking on a treadmill. Joint angles and segment motion were analyzed quantitatively, and complexity of joint angle trajectory and overall gait were calculated using permutation entropy and principal component analysis, respectively. Following treadmill testing, the animals were euthanized and hindlimb muscles removed. Excised muscles were tested for mass, density, fiber length, pennation angle, and relaxed sarcomere length. Results Muscle parameters were similar between groups with no evidence of muscle atrophy. The animals showed overextension of the ankle, which was compensated for by a decreased range of motion at the knee. Left-right coordination was altered, leading to left and right knee movements that are entirely out of phase, with one joint moving while the other is stationary. Movement patterns remained symmetric. Permutation entropy measures indicated changes in complexity on a joint specific basis, with the largest changes at the ankle. No significant difference was seen using principal component analysis. Rats were able to achieve stable weight bearing locomotion at reasonable speeds on the treadmill despite these deficiencies. Conclusions Decrease in supraspinal control following iSCI causes a loss of complexity of ankle kinematics. This loss can be entirely due to loss of supraspinal control in the absence of muscle atrophy and may be quantified using permutation entropy. Joint-specific differences in kinematic complexity may be attributed to different sources of motor control. This work indicates the importance of the ankle for rehabilitation interventions following spinal cord injury.

Proton Form Factor Puzzle and the CEBAF Large Acceptance Spectrometer (CLAS) two-photon exchange experiment

The electromagnetic form factors are the most fundamental observables that encode information about the internal structure of the nucleon. The electric (GE) and the magnetic ( GM) form factors contain information about the spatial distribution of the charge and magnetization inside the nucleon. A significant discrepancy exists between the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors of the proton. One possible explanation for the discrepancy is the contributions of two-photon exchange (TPE) effects. Theoretical calculations estimating the magnitude of the TPE effect are highly model dependent, and limited experimental evidence for such effects exists. Experimentally, the TPE effect can be measured by comparing the ratio of positron-proton elastic scattering cross section to that of the electron-proton [R = σ(e +p)/σ(e+p)]. The ratio R was measured over a wide range of kinematics, utilizing a 5.6 GeV primary electron beam produced by the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. This dissertation explored dependence of R on kinematic variables such as squared four-momentum transfer (Q2) and the virtual photon polarization parameter (&epsis;). A mixed electron-positron beam was produced from the primary electron beam in experimental Hall B. The mixed beam was scattered from a liquid hydrogen (LH2) target. Both the scattered lepton and the recoil proton were detected by the CEBAF Large Acceptance Spectrometer (CLAS). The elastic events were then identified by using elastic scattering kinematics. This work extracted the Q2 dependence of R at high &epsis;(&epsis; > 0.8) and the $&epsis; dependence of R at ⟨Q 2⟩ approx 0.85 GeV2. In these kinematics, our data confirm the validity of the hadronic calculations of the TPE effect by Blunden, Melnitchouk, and Tjon. This hadronic TPE effect, with additional corrections contributed by higher excitations of the intermediate state nucleon, largely reconciles the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors.

The H I chronicles of LITTLE THINGS blue compact dwarf galaxies

Star formation occurs when the gas (mostly atomic hydrogen; H I) in a galaxy becomes disturbed, forming regions of high density gas, which then collapses to form stars. In dwarf galaxies it is still uncertain which processes contribute to star formation and how much they contribute to star formation. Blue compact dwarf (BCD) galaxies are low mass, low shear, gas rich galaxies that have high star formation rates when compared to other dwarf galaxies. What triggers the dense burst of star formation in BCDs but not other dwarfs is not well understood. It is often suggested that BCDs may have their starburst triggered by gravitational interactions with other galaxies, dwarf-dwarf galaxy mergers, or consumption of intergalactic gas. However, there are BCDs that appear isolated with respect to other galaxies, making an external disturbance unlikely.^ Here, I study six apparently isolated BCDs from the LITTLE THINGS sample in an attempt to understand what has triggered their burst of star formation. LITTLE THINGS is an H I survey of 41 dwarf galaxies. Each galaxy has high angular and velocity resolution H I data from the Very Large Array (VLA) telescope and ancillary stellar data. I use these data to study the detailed morphology and kinematics of each galaxy, looking for signatures of starburst triggers. In addition to the VLA data, I have collected Green Bank Telescope data for the six BCDs. These high sensitivity, low resolution data are used to search the surrounding area of each galaxy for extended emission and possible nearby companion galaxies.^ The VLA data show evidence that each BCD has likely experienced some form of external disturbance despite their apparent isolation. These external disturbances potentially seen in the sample include: ongoing/advanced dwarf-dwarf mergers, an interaction with an unknown external object, and external gas consumption. The GBT data result in no nearby, separate H I companions at the sensitivity of the data. These data therefore suggest that even though these BCDs appear isolated, they have not been evolving in isolation. It is possible that these external disturbances may have triggered the starbursts that defines them as BCDs.^

Exclusive electrodisintegration of three-nucleon systems

The purpose of this research was to develop a theory of high-energy exclusive electrodisintegration of three-nucleon systems on the example of 3He(e, e'NN)N reaction with knocked-out nucleon in the final state. The scattering amplitudes and differential cross section of the reaction were calculated in details within the Generalized Eikonal Approximation(GEA). The manifestly covariant nature of Feynman diagrams derived in GEA allowed us to preserve both the relativistic dynamics and kinematics of the scattering while identifying the low momentum nuclear part of the amplitude with a nonrelativistic nuclear wave function. Numerical calculations of the residual system's total and relative momentum distribution were performed which show reasonable agreement with available experimental data. The theoretical framework of GEA, which was applied previously only for the case of two-body (deuteron) high energy break up reactions, has been practically implemented and shown to provide a valid description for more complex A = 3 systems.

Neuromuscular Changes in Older Adults during the Lateral Step Task

Older adults may have trouble when performing activities of daily living due to decrease in physical strength and degradation of neuromotor and musculoskeletal function. Motor activation patterns during Lateral Step Down and Step Up from 4-inch and 8-inch step heights was assessed in younger (n=8, 24.4 years) and older adults (n=8, 58.9 years) using joint angle kinematics and electromyography of lower extremity muscles. Ground reaction forces were used to ascertain the loading, stabilization and unloading phases of the tasks. Older adults had an altered muscle activation sequence and significantly longer muscle bursts during loading for the tibialis anterior, gastrocnemius, vastus medialis, bicep femoris, gluteus medius and gluteus maximus muscles of the stationary leg. They also demonstrated a significantly larger swing time (579.1 ms vs. 444.8 ms) during the step down task for the moving leg. The novel data suggests presence of age-related differences in motor coordination during lateral stepping.

Gravidade do olho seco em pacientes internados em unidade de terapia intensiva: análise de conceito e construção de definições

Dry eye syndrome is a multifactorial disease of the tear film, resulting from the instability of the lacrimal functional unit that produces volume change, up or tear distribution. In patients in intensive care the cause is enhanced due to various risk factors, such as mechanical ventilation, sedation, lagophthalmos, low temperatures, among others. The study's purpose is to build an assessment tool of Dry Eye Severity in patients in intensive care units based on the systematization of nursing care and their classification systems. The aim of this study is to build an assessment tool of Dry Eye Severity in hospitalized patients in Care Unit Intensiva.Trata is a methodological study conducted in three stages, namely: context analysis, concept analysis, construction of operational definitions and magnitudes of nursing outcome. For the first step we used the methodological framework for Hinds, Chaves and Cypress (1992). For the second step we used the model of Walker and Avant and an integrative review Whitemore seconds, Knalf (2005). This step enabled the identification of the concept of attributes, background and consequent ground and the construction of the settings for the result of nursing severity of dry eye. For the construction of settings and operational magnitudes, it was used Psicometria proposed by Pasquali (1999). As a result of context analysis, visualized from the reflection that the matter should be discussed and that nursing needs to pay attention to the problem of eye injury, so minimizing strategies are created this event with a high prevalence. With the integrative review were located from the crosses 19 853 titles, selected 215, and from the abstracts 96 articles were read in full. From reading 10 were excluded culminating in the sample of 86 articles that were used to analyze the concept and construction of settings. Selected articles were found in greater numbers in the Scopus database (55.82%), performed in the United States (39.53%), and published mainly in the last five years (48.82). Regarding the concept of analysis were identified as antecedents: age, lagophthalmos, environmental factors, medication use, systemic diseases, mechanical ventilation and ophthalmic surgery. As attributes: TBUT <10s, Schimer I test <5 mm in Schimer II test <10mm, reduced osmolarity. As consequential: the ocular surface damage, ocular discomfort, visual instability. The settings were built and added indicators such as: decreased blink mechanism and eyestrain.

Petrologia e geologia estrutural do plutão granítico Barcelona, província Borborema, NE do Brasil

The Dissertation aimed to advance the geological knowledge of the Barcelona Granitic Pluton (BGP). This body is located in the eastern portion of the Rio Grande do Norte Domain (RND), within the São José do Campestre subdomain (SJC), NE of the Borborema Province. The main goal was to understand the geological evolution of the rocks of the pluton and the tectonic setting of magma generation and its emplacement. The BGP has an assumed Ediacaran age and outcropping area of approximately 260 km2, being composed of three varied petrographic/textural facies: (a) porphyritic biotite monzogranite; (b) dykes and sheets of biotite microgranite; (c) dioritic to quartz-dioritic enclaves. The rocks of the BGP have the following structures: (i) a NE-SW and NW-SE directed magmatic fabric (Sγ), accompanied by a magmatic lineation (Lγ) with gentle dip to NE-SW and NW-SE. In the southern portion, there is the concentric pattern of this foliation with medium to high dip, and (ii) a solid state foliation, in part mylonitic (S3+), mainly on the eastern edge with slightly plunging to west. The integration of structural and gravity data permitted to interpret the emplacement of the BGP as controlled by the transcurrent shear zones systems Lajes Pintadas (LPSZ) and Sítio Novo (SNSZ), both of dextral strike-slip kinematics. Mineral chemistry data show that the amphibole form the porphyritic biotite monzogranite facies is hastingsite with moderate Mg / (Mg + Fe) ratios, indicating crystallization under moderate to high ƒO2 and cristallization pressure of around 5.0-6.0 kbar. The biotite tends to be slightly richer in annite molecule and plots in the transitional field from primary biotite to reequilibrated biotite. In discriminant diagrams of magmatic series, the biotite behave like those of subalkaline affinity, consistent with the potassium calc-alkaline / sub-alkaline geochemical affinity of the hosting rock. The opaque minerals are primarily magnetite, with some crystals martitized to hematite indicating relatively oxidizing conditions during magma evolution that originated the BGP. Zoning in plagioclase, K-feldspar and allanite crystals suggest fractional crystallization process. Lithogeochemical data suggest that the facies described for the BGP have similar magma source, usually plotting in the fields and trends of the subalkaline / high potassium calc-alkaline series.

Expressão geofísica-estrutural do lineamento transbrasiliano na porção central da Bacia do Parnaíba (Maranhão-Piauí)

The objective of this study was to characterize the structural-geophysical expression of the Transbrasiliano Lineament (TBL) in the east-central portion of the Parnaíba Basin. The TBL corresponds to a major Neoproterozoic NE-trending shear zone related to the Brasiliano orogenic cycle, with dextral strike-slip kinematics, underlying (but also laterally exposed in the NE and SW basin edges) the sedimentary section of the Parnaíba Basin. In this study, the interpretation of gravity and magnetic anomaly maps is consistent with the TBL kinematics, the signature of the geophysical anomalies corresponding to the high (plastic behaviour) and subsequent declining temperature (ductile to brittle behaviour) stages during Brasiliano and late Brasiliano times. The pattern of residual gravity anomalies is compatible with an S-C dextral pair shaping the geological bodies of an heterogeneous basement, such as slices of gneisses and granulites (positive anomalies), granitic and low-medium grade metasedimentary rocks (negative anomalies). Such anomalies curvilinear trends, ranging from NNE (interpreted as S surfaces) to NE (C surfaces), correspond to flattening surfaces (S), while the NE rectilinear trend must represent a C band. The narrower magnetic anomalies also display NNE to NE (S surfaces) trends and should correspond to similar (although narrower and more discontinuous) sources in the equivalent anomaly patterns. Pre-Silurian pull-apart style grabens may contribute to the NE negative gravimetric anomalies, although this interpretation demands control by seismic data analysis. On the other hand, the curvilinear anomalies associated to contractional trends are incompatible with their interpretation as pre-Silurian graben, in both maps. In the (reduced to the pole) magnetic anomalies map, most of these are again associated to low-temperature shear zones (C planes) and faults, juxtaposing distinct blocks in terms of magnetic properties, or eventually filled with basic bodies. It is also possible that some isolated magnetic anomalies correspond to igneous bodies of late-Brasiliano or Mesozoic age. The basement late discontinuities pattern can be interpreted in analogy to the Riedel fractures model, with steep dipping surfaces and a sub-horizontal movement section. This study also explored 2D gravity modeling controlled by the interpretation of a dip seismic line as regards to the Transbrasiliano Lineament. The rock section equivalent to the Jaibaras Group occupying a graben structure (as identified in the seismic line) corresponds to a discrete negative anomaly superimposed to a gravimetric high, once again indicating a stronger influence of older crystalline basement rocks as gravimetric sources, mainly reflecting the heterogeneities and anisotropies generated at high temperature conditions and their subsequent cooling along the TBL, during the Brasiliano cycle.