Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR).

OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP?

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used.

REVIEW METHODS: Systematic review and economic modelling.

RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO.

LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR.

CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Kinetics of methylene blue (MB) photocatalyzed reduction and dark regeneration in a colorimetric oxygen sensor

Performance data for a dye based, regenerable oxygen sensor (Mills and Lawrie [1], Mills et al. [2]) are analyzed to develop useful kinetic models for sensor photoactivation (dye reduction) and dark, oxygen detection (dye oxidation). The titania loaded, thin film sensor exhibits an apparent first order photoactivation of the dye, which we demonstrate (Section 3.2 and Fig. 4) is due to a kinetic disguise of a zero order photoreaction occurring through a non-uniformly illuminated sensor film. The observed zero order, slow recovery due to dye oxidation by dioxygen (O2 detection) appears best rationalized by a model assuming a near O2-impermeable skin developing on the sensor surface as solvent is evaporatively removed following sensor film casting and curing.

An effective key generation system using improved channel reciprocity

In physical layer security systems there is a clear need to exploit the radio link characteristics to automatically generate an encryption key between two end points. The success of the key generation depends on the channel reciprocity, which is impacted by the non-simultaneous measurements and the white nature of the noise. In this paper, an OFDM subcarriers' channel responses based key generation system with enhanced channel reciprocity is proposed. By theoretically modelling the OFDM subcarriers' channel responses, the channel reciprocity is modelled and analyzed. A low pass filter is accordingly designed to improve the channel reciprocity by suppressing the noise. This feature is essential in low SNR environments in order to reduce the risk of the failure of the information reconciliation phase during key generation. The simulation results show that the low pass filter improves the channel reciprocity, decreases the key disagreement, and effectively increases the success of the key generation.

Language Experience Affects Grouping of Musical Instrument Sounds

Language experience clearly affects the perception of speech, but little is known about whether these differences in perception extend to non-speech sounds. In this study, we investigated rhythmic perception of non-linguistic sounds in speakers of French and German using a grouping task, in which complexity (variability in sounds, presence of pauses) was manipulated. In this task, participants grouped sequences of auditory chimeras formed from musical instruments. These chimeras mimic the complexity of speech without being speech. We found that, while showing the same overall grouping preferences, the German speakers showed stronger biases than the French speakers in grouping complex sequences. Sound variability reduced all participants' biases, resulting in the French group showing no grouping preference for the most variable sequences, though this reduction was attenuated by musical experience. In sum, this study demonstrates that linguistic experience, musical experience, and complexity affect rhythmic grouping of non-linguistic sounds and suggests that experience with acoustic cues in a meaningful context (language or music) is necessary for developing a robust grouping preference that survives acoustic variability.

Understanding the non-pharmacological correlates of self-reported efficacy of antidepressants

Objective: To explore the non-pharmacological correlates of the perceived effectiveness of antidepressants (ADs), thereby enhancing understanding of the mechanisms involved in recovery from depression while taking ADs. Method: An online survey was completed by 1781 New Zealand adults who had taken ADs in the previous 5 years. Results: All 18 psychosocial variables measured were associated with depression reduction, and 16 with improved quality of life (QoL). Logistic regression models revealed that the quality of the relationship with the prescriber was related to both depression reduction and improved QoL. In addition, depression reduction was related to younger age, higher income, being fully informed about ADs by the prescriber, fewer social causal beliefs for depression and not having lost a loved one in the 2 months prior to prescription. Furthermore, both outcome measures were positively related to belief in ‘chemical’ rather than ‘placebo’ effects. Conclusion: There are multiple non-pharmacological processes involved in recovery while taking ADs. Enhancing them, for example focusing on the prescriber–patient relationship and giving more information, may enhance recovery rates, with or without ADs.

Non-linear analysis of piezolaminated structures

In the recent years the study of smart structures has attracted significant researchers, due to their potential benefits in a wide range of applications, such as shape control, vibration suppression, noise attenuation and damage detection. The applications in aerospace industry are of great relevance, such as in active control of airplane wings, helicopter blade rotor, space antenna. The use of smart materials, such as piezoelectric materials, in the form of layers or patches embedded and/or surface bonded on laminated composite structures, can provide structures that combine the superior mechanical properties of composite materials and the capability to sense and adapt their static and dynamic response, becoming adaptive structures. The piezoelectric materials have the property of generate electrical charge under mechanical load or deformation, and the reverse, applying an electrical field to the material results in mechanical strain or stresses.

EU water framework directive: will the nitrate load reduction from diffuse sources produce the same results in all estuaries?

The impact of urban waste-water and non-point nitrate discharges in estuarine and near-shore coastal waters are analyzed. The study is focused on the effects of applying the European directives 91/271/EEC and 91/676/EEC to these systems. 4 Portuguese estuaries and two coastal lagoons with different characteristics are studied. A modelling system is applied and calibrated in each system. Three nitrate load scenarios are examined. It is shown that the morphologic and hydrodynamic characteristics of the domain largely control the ecological processes in these systems. The primary production limitation factors are split into “biologic” and “hydrodynamic” components. The physical limitation due to hydrodynamic and residence time is the most important factor. The combined limitation of “biologic” factors (temperature, light and nutrients availability) control productivity only in the systems where physical limitation is not important.

Electrical characterization of metal-oxide-polymer devices for non-volatile memory applications

The objective of this thesis is to study the properties of resistive switching effect based on bistable resistive memory which is fabricated in the form of Al2O3/polymer diodes and to contribute to the elucidation of resistive switching mechanisms. Resistive memories were characterized using a variety of electrical techniques, including current-voltage measurements, small-signal impedance, and electrical noise based techniques. All the measurements were carried out over a large temperature range. Fast voltage ramps were used to elucidate the dynamic response of the memory to rapid varying electric fields. The temperature dependence of the current provided insight into the role of trapped charges in resistive switching. The analysis of fast current fluctuations using electric noise techniques contributed to the elucidation of the kinetics involved in filament formation/rupture, the filament size and correspondent current capabilities. The results reported in this thesis provide insight into a number of issues namely: (i) The fundamental limitations on the speed of operation of a bi-layer resistive memory are the time and voltage dependences of the switch-on mechanism. (ii) The results explain the wide spread in switching times reported in the literature and the apparently anomalous behaviour of the high conductance state namely the disappearance of the negative differential resistance region at high voltage scan rates which is commonly attributed to a “dead time” phenomenon which had remained elusive since it was first reported in the ‘60s. (iii) Assuming that the current is filamentary, Comsol simulations were performed and used to explain the observed dynamic properties of the current-voltage characteristics. Furthermore, the simulations suggest that filaments can interact with each other. (iv) The current-voltage characteristics have been studied as a function of temperature. The findings indicate that creation and annihilation of filaments is controlled by filling and neutralizing traps localized at the oxide/polymer interface. (v) Resistive switching was also studied in small-molecule OLEDs. It was shown that the degradation that leads to a loss of light output during operation is caused by the presence of a resistive switching layer. A diagnostic tool that predicts premature failure of OLEDs was devised and proposed. Resistive switching is a property of oxides. These layers can grow in a number of devices including, organic light emitting diodes (OLEDs), spin-valve transistors and photovoltaic devices fabricated in different types of material. Under strong electric fields the oxides can undergo dielectric breakdown and become resistive switching layers. Resistive switching strongly modifies the charge injection causing a number of deleterious effects and eventually device failure. In this respect the findings in this thesis are relevant to understand reliability issues in devices across a very broad field.

Ocean bottom seismic noise : applications for the crust knowledge, interaction ocean-atmosphere and instrumental behaviour

Tese de doutoramento, Ciências Geofísicas e da Geoinformação (Geofisíca), Universidade de Lisboa, Faculdade de Ciências, 2014

Adaptive modeling and high quality spectral estimation for speech enhancement

In this work an adaptive modeling and spectral estimation scheme based on a dual Discrete Kalman Filtering (DKF) is proposed for speech enhancement. Both speech and noise signals are modeled by an autoregressive structure which provides an underlying time frame dependency and improves time-frequency resolution. The model parameters are arranged to obtain a combined state-space model and are also used to calculate instantaneous power spectral density estimates. The speech enhancement is performed by a dual discrete Kalman filter that simultaneously gives estimates for the models and the signals. This approach is particularly useful as a pre-processing module for parametric based speech recognition systems that rely on spectral time dependent models. The system performance has been evaluated by a set of human listeners and by spectral distances. In both cases the use of this pre-processing module has led to improved results.

Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers

BACKGROUND: Highway maintenance workers are constantly and simultaneously exposed to traffic-related particle and noise emissions, and both have been linked to increased cardiovascular morbidity and mortality in population-based epidemiology studies. OBJECTIVES: We aimed to investigate short-term health effects related to particle and noise exposure. METHODS: We monitored 18 maintenance workers, during as many as five 24-hour periods from a total of 50 observation days. We measured their exposure to fine particulate matter (PM2.5), ultrafine particles, noise, and the cardiopulmonary health endpoints: blood pressure, pro-inflammatory and pro-thrombotic markers in the blood, lung function and fractional exhaled nitric oxide (FeNO) measured approximately 15 hours post-work. Heart rate variability was assessed during a sleep period approximately 10 hours post-work. RESULTS: PM2.5 exposure was significantly associated with C-reactive protein and serum amyloid A, and negatively associated with tumor necrosis factor α. None of the particle metrics were significantly associated with von Willebrand factor or tissue factor expression. PM2.5 and work noise were associated with markers of increased heart rate variability, and with increased HF and LF power. Systolic and diastolic blood pressure on the following morning were significantly associated with noise exposure after work, and non-significantly associated with PM2.5. We observed no significant associations between any of the exposures and lung function or FeNO. CONCLUSIONS: Our findings suggest that exposure to particles and noise during highway maintenance work might pose a cardiovascular health risk. Actions to reduce these exposures could lead to better health for this population of workers.

Predicting trabecular bone microdamage initiation and accumulation using a non-linear perfect damage model

Studies evaluating the mechanical behavior of the trabecular microstructure play an important role in our understanding of pathologies such as osteoporosis, and in increasing our understanding of bone fracture and bone adaptation. Understanding of such behavior in bone is important for predicting and providing early treatment of fractures. The objective of this study is to present a numerical model for studying the initiation and accumulation of trabecular bone microdamage in both the pre- and post-yield regions. A sub-region of human vertebral trabecular bone was analyzed using a uniformly loaded anatomically accurate microstructural three-dimensional finite element model. The evolution of trabecular bone microdamage was governed using a non-linear, modulus reduction, perfect damage approach derived from a generalized plasticity stress-strain law. The model introduced in this paper establishes a history of microdamage evolution in both the pre- and post-yield regions

Engorgement des centres d'urgences: une raison légitime de refuser l'accès aux patients non urgents [Emergency department overcrowding: a legitimate reason to refuse access to urgent care for non-urgent patients?].

Non-urgent cases represent 30-40% of all ED consults; they contribute to overcrowding of emergency departments (ED), which could be reduced if they were denied emergency care. However, no triage instrument has demonstrated a high enough degree of accuracy to safely rule out serious medical conditions: patients suffering from life-threatening emergencies have been inappropriately denied care. Insurance companies have instituted financial penalties to discourage the use of ED as a source of non-urgent care, but this practice mainly restricts access for the underprivileged. More recent data suggest that in fact most patients consult for appropriate urgent reasons, or have no alternate access to urgent care. The safe reduction of overcrowding requires a reform of the healthcare system based on patients' needs rather than access barriers.

Practical signal-to-noise ratio quantification for sensitivity encoding: Application to coronary MR angiography.

Purpose: To develop and evaluate a practical method for the quantification of signal-to-noise ratio (SNR) on coronary MR angiograms (MRA) acquired with parallel imaging.Materials and Methods: To quantify the spatially varying noise due to parallel imaging reconstruction, a new method has been implemented incorporating image data acquisition followed by a fast noise scan during which radio-frequency pulses, cardiac triggering and navigator gating are disabled. The performance of this method was evaluated in a phantom study where SNR measurements were compared with those of a reference standard (multiple repetitions). Subsequently, SNR of myocardium and posterior skeletal muscle was determined on in vivo human coronary MRA.Results: In a phantom, the SNR measured using the proposed method deviated less than 10.1% from the reference method for small geometry factors (<= 2). In vivo, the noise scan for a 10 min coronary MRA acquisition was acquired in 30 s. Higher signal and lower SNR, due to spatially varying noise, were found in myocardium compared with posterior skeletal muscle.Conclusion: SNR quantification based on a fast noise scan is a validated and easy-to-use method when applied to three-dimensional coronary MRA obtained with parallel imaging as long as the geometry factor remains low.

Temporal SNR characteristics in segmented 3D-EPI at 7T.

Three-dimensional segmented echo planar imaging (3D-EPI) is a promising approach for high-resolution functional magnetic resonance imaging, as it provides an increased signal-to-noise ratio (SNR) at similar temporal resolution to traditional multislice 2D-EPI readouts. Recently, the 3D-EPI technique has become more frequently used and it is important to better understand its implications for fMRI. In this study, the temporal SNR characteristics of 3D-EPI with varying numbers of segments are studied. It is shown that, in humans, the temporal variance increases with the number of segments used to form the EPI acquisition and that for segmented acquisitions, the maximum available temporal SNR is reduced compared to single shot acquisitions. This reduction with increased segmentation is not found in phantom data and thus likely due to physiological processes. When operating in the thermal noise dominated regime, fMRI experiments with a motor task revealed that the 3D variant outperforms the 2D-EPI in terms of temporal SNR and sensitivity to detect activated brain regions. Thus, the theoretical SNR advantage of a segmented 3D-EPI sequence for fMRI only exists in a low SNR situation. However, other advantages of 3D-EPI, such as the application of parallel imaging techniques in two dimensions and the low specific absorption rate requirements, may encourage the use of the 3D-EPI sequence for fMRI in situations with higher SNR.