João Rafael de Oliveira Dias

Hoopl: a modular, reusable library for dataflow analysis and transformation

Dataflow analysis and transformation of control-flow graphs is pervasive in optimizing compilers, but it is typically entangled with the details of a particular compiler. We describe Hoopl, a reusable library that makes it unusually easy to define new analyses and transformations for any compiler written in Haskell. Hoopls interface is modular and polymorphic, and it offers unusually strong static guarantees. The implementation encapsulates state-of-the-art algorithms (interleaved analysis and rewriting, dynamic error isolation), and it cleanly separates their tricky elements so that they can be understood independently.

Intravitreal Injection of Ziv-Aflibercept in Patient With Refractory Age-Related Macular Degeneration

The results of a patient with exudative age-related macular degeneration who received an intravitreal injection of ziv-aflibercept (Zaltrap; Sanofi-Aventis, Paris, France) in the right eye are described. A complete ocular examination as well as color fundus photography, optical coherence tomography, fluorescein angiography, microperimetry, full-field electroretinography, and multifocal electroretinography were performed and repeated 1 month later. The patient experienced subjective and objective improvement of visual acuity with a decrease in intraretinal and subretinal fluid. Microperimetric improvement also occurred. Electroretinographic changes were noted from baseline to the 30-day follow-up. No adverse events were observed at any time point. Ziv-aflibercept demonstrated short-term safety and efficacy after intravitreal administration for neovascular macular degeneration.

Preclinical investigations of intravitreal ziv-aflibercept.

BACKGROUND AND OBJECTIVE To investigate the retinal safety of intravitreal (IVT) ziv-aflibercept in rabbits. MATERIALS AND METHODS Eighteen rabbits were given an IVT injection of ziv-aflibercept (25 mg/mL) or aflibercept (40 mg/mL) and examined by funduscopy, electroretinography (ERG), optical coherence tomography (OCT), light microscopy, and transmission electron microscopy (TEM). Serum, aqueous, and vitreous were obtained afterward for osmolarity analysis. The effect of ziv-aflibercept on human retinal cultured cells (ARPE-19) was assessed by the MTT cell viability assay. RESULTS All eyes showed normal funduscopy, OCT, and ERG findings at baseline and 24 hours or 7 days after the procedure. Median baseline serum, vitreous, and aqueous osmolarity remained unchanged. Histology and TEM showed no major anatomic signs of toxicity. No cytotoxic effect was observed in ARPE-19 cells exposed to ziv-aflibercept. CONCLUSION IVT injection ziv-aflibercept at a concentration of 25 mg/mL proved to be safe for the rabbit retina.

INFANTS WITH CONGENITAL ZIKA SYNDROME AND OCULAR FINDINGS FROM SÃO PAULO, BRAZIL: SPREAD OF INFECTION.

Background/Purpose: To describe the ocular findings of two infants with congenital Zika syndrome born in São Paulo state, Brazil, outside the primary outbreak region. Methods: Two female infants with congenital Zika syndrome were submitted to a complete screening for infectious diseases, as well as ocular examination, fundus photography, and optical coherence tomography of the retina. One of the infants was submitted to ocular ultrasound. Results: Both children showed positive serology for Zika virus, and other infectious diseases were ruled out. On fundus examination, one newborn had extensive bilateral macular chorioretinal atrophy with hyperpigmented borders associated with gross pigment mottling, as well as atrophic well-limited roundish peripheral lesions in the right eye. Spectral domain optical coherence tomography of the right eye showed complete chorioretinal atrophy in the temporal quadrant. The other infant presented bilateral gross pigment mottling in a paramacular location and a normal optical coherence tomography. Discussion: In this report, the ophthalmologic findings of two infants with Zika syndrome and ocular findings born in São Paulo state, Brazil, are described. Optical coherence tomography findings demonstrate the broad range of retinal damage caused by congenital Zika virus infection. Conclusion: The autochthonous cases of infants with congenital Zika syndrome and ocular findings described in this report demonstrate that Zika virus infection is not limited to northeast Brazil, with the potential for even greater spread.

Converting intermediate code to assembly code using declarative machine descriptions

Writing an optimizing back end is expensive, in part because it requires mastery of both a target machine and a compilers internals. We separate these concerns by isolating target-machine knowledge in declarative machine descriptions. We then analyze these descriptions to automatically generate machine-specific components of the back end. In this work, we generate a recognizer; this component, which identifies register transfers that correspond to target-machine instructions, plays a key role in instruction selection in such compilers as vpo, gcc and Quick C–. We present analyses and transformations that address the major challenge in generating a recognizer: accounting for compile-time abstractions not present in a machine description, including variables, pseudo-registers, stack slots, and labels.

Automatically generating instruction selectors using declarative machine descriptions

Despite years of work on retargetable compilers, creating a good, reliable back end for an optimizing compiler still entails a lot of hard work. Moreover, a critical component of the back end---the instruction selector---must be written by a person who is expert in both the compilers intermediate code and the target machines instruction set. By generating the instruction selector from declarative machine descriptions we have (a) made it unnecessary for one person to be both a compiler expert and a machine expert, and (b) made creating an optimizing back end easier than ever before. Our achievement rests on two new results. First, finding a mapping from intermediate code to machine code is an undecidable problem. Second, using heuristic search, we can find mappings for machines of practical interest in at most a few minutes of CPU time. Our most significant new idea is that heuristic search should be controlled by algebraic laws. Laws are used not only to show when a sequence of instructions implements part of an intermediate code, but also to limit the search: we drop a sequence of instructions not when it gets too long or when it computes too complicated a result, but when too much reasoning will be required to show that the result computed might be useful.

Clinical And Electrophysiological Evaluation After Intravitreal Ziv-aflibercept For Exudative Age-related Macular Degeneration

Purpose: To evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration. Methods: Fifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment. Results: Between baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm3 to 8.08 ± 1.34 mm3, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed. Conclusion: Intravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.

An Applicative Control-Flow Graph Based on Huet's Zipper

We are using ML to build a compiler that does low-level optimization. To support optimizations in classic imperative style, we built a control-flow graph using mutable pointers and other mutable state in the nodes. This decision proved unfortunate: the mutable flow graph was big and complex, and it led to many bugs. We have replaced it by a smaller, simpler, applicative flow graph based on Huets [Huet, Gerard, 1997. The Zipper. Journal of Functional Programming, 7(5):549-554. Functional Pearl] zipper. The new flow graph is a success; this paper presents its design and shows how it leads to a gratifyingly simple implementation of the dataflow framework developed by [Lerner, Sorin, David Grove, and Craig Chambers. 2002. Composing dataflow analyses and transformations. Conference Record of the 29th Annual ACM Symposium on Principles of Programming Languages, in SIGPLAN Notices, 31(1):270-282].

Optical Coherence Tomography Angiography of Chorioretinal Diseases.

Fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been the gold standard for the evaluation of retinal and choroidal vasculature in the last three decades and have revolutionized the diagnosis of retinal and choroidal vascular diseases. The advantage of these imaging modalities lies in their ability to document retinal and choroidal vasculature through the dynamic assessment of contrast transit over time in the intravascular and extravascular spaces. However, disadvantages include the absence of depth resolution, blurring of details by contrast leakage, and the inability to selectively evaluate different levels of the retinal and choroidal microvasculature. In addition, these angiographic methods require intravenous dye, which may cause adverse reactions such as nausea, vomiting, and rarely, anaphylaxis. Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that, in contrast to dye-based angiography, is faster and depth-resolved, allowing in some cases for more precise evaluation of the vascular plexuses of the retina and choroid. The method has been demonstrated in the assessment of various vascular diseases such as venous occlusions, diabetic retinopathy, macular neovascularization, and others. Limitations of this imaging modality include a small registered field of view and the inability to visualize leakage and dye transit over time. It is also subject to a variety of artifacts, including those generated by blinking and eye movement during image acquisition. However, more than an alternative for FA and ICGA, OCTA is bringing new insights to our understanding of retinal and choroidal vascular structure and is changing fundamental paradigms in the clinical management of pathologic conditions. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:848-861.].

Intravitreal Ziv-Aflibercept for Diabetic Macular Edema: 48-Week Outcomes

BACKGROUND AND OBJECTIVE To study the safety and efficacy of intravitreal injections of ziv-aflibercept (IVI-ZA) (Zaltrap; Sanofi-Aventis and Regeneron Pharmaceuticals, Tarrytown, NY) during a period of 48 weeks in patients with diabetic macular edema (DME). PATIENTS AND METHODS Seven consecutive patients with DME were enrolled and submitted to 12 consecutive IVI-ZA with a 4-week interval. The safety parameters included changes in full-field electroretinogram (ERG) and systemic or ocular complications, and the efficacy parameters were the mean change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS No significant differences were found in any ERG component after IVI-ZA, and no systemic or ocular complication was observed. The improvement of BCVA was most significant after the first IVI-ZA and remained until week 48 (P < .05). The CRT significantly decreased during the course of 48 weeks. CONCLUSION The 48-week results are consistent with our previous 24-week findings, supporting IVI-ZA as a safe, efficient, and well-tolerated therapy for patients with DME. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:245-250.].