Prophylactic non-steroidal anti-inflammatory drugs for the prevention of macular oedema after cataract surgery.

BACKGROUND: Macular oedema (MO) is the accumulation of extracellular fluid in the central retina (the macula). It may occur after cataract surgery and may give rise to poor visual outcome, with reduced visual acuity and distortion of the central vision. MO is often self-limiting with spontaneous resolution, but a small proportion of people with chronic persistent MO may be difficult to treat. Chronic oedema may lead to the formation of cystic spaces in the retina termed 'cystoid macular oedema' (CMO). Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in cataract surgery and may reduce the chances of developing MO. OBJECTIVES: The aim of this review is to answer the question: is there evidence to support the prophylactic use of topical NSAIDs either in addition to, or instead of, topical steroids postoperatively to reduce the incidence of macular oedema (MO) and associated visual morbidity. SEARCH METHODS: We searched a number of electronic databases including CENTRAL, MEDLINE and Embase. Date last searched 2 September 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which adult participants had undergone surgery for age-related cataract. We included participants irrespective of their baseline risk of MO, in particular we included people with diabetes and uveitis. We included trials of preoperative and/or postoperative topical NSAIDs in conjunction with postoperative topical steroids. The comparator was postoperative topical steroids alone. A secondary comparison was preoperative and/or postoperative topical NSAIDs alone versus postoperative topical steroids alone. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed risk of bias and extracted data using standard methods expected by Cochrane. We pooled data using a random-effects model. We graded the certainty of the evidence using GRADE and considered the following: risk of bias of included studies, precision of the effect estimate, consistency of effects between studies, directness of the outcome measure and publication bias. MAIN RESULTS: We identified 34 studies that were conducted in the Americas, Europe, the Eastern Mediterranean region and South-East Asia. Over 5000 people were randomised in these trials. The majority of studies enrolled one eye per participant; a small subset (4 trials) enrolled a proportion of people with bilateral surgery. Twenty-eight studies compared NSAIDs plus steroids with steroids alone. Six studies compared NSAIDs with steroids. A variety of NSAIDs were used, including ketorolac, diclofenac, nepafenac, indomethacin, bromfenac, flurbiprofen and pranopfen. Follow-up ranged from one to 12 months. In general, the studies were poorly reported. We did not judge any of the studies at low risk of bias in all domains. Six studies were funded by industry, seven studies were funded from non-industry sources, and the rest of the studies did not report the source of funding.There was low-certainty evidence that people receiving topical NSAIDs in combination with steroids may have a lower risk of poor vision due to MO at three months after cataract surgery compared with people receiving steroids alone (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.23 to 0.76; eyes = 1360; studies = 5; I2 = 5%). We judged this to be low-certainty evidence because of risk of bias in the included studies and indirectness, as the extent of visual loss was not always clear. Only one study reported poor vision due to MO at 12 months and we judged this to be very low-certainty evidence as there were only two events. Quality of life was only reported in one of the 34 studies comparing NSAIDs plus steroids versus steroids alone, and it was not fully reported, other than to comment on lack of differences between groups. There was evidence of a reduced risk of MO with NSAIDs at three months after surgery, but we judged this to be low-certainty due to risk of bias and publication bias (RR 0.40, 95% CI 0.32 to 0.49; eyes = 3638; studies = 21). There was inconsistent evidence on central retinal thickness at three months (I2 = 87%). Results ranged from -30.9 µm in favour of NSAIDs plus steroids to 7.44 µm in favour of steroids alone. Similarly, data on best corrected visual acuity (BCVA) were inconsistent, but nine out of 10 trials reporting this outcome found between-group differences in visual acuity of less than 0.1 logMAR.None of the six studies comparing NSAIDs alone with steroids reported on poor vision due to MO at three or 12 months. There was low-certainty evidence that central retinal thickness was lower in the NSAIDs group at three months (mean difference (MD) -22.64 µm, 95% CI -38.86 to -6.43; eyes = 121; studies = 2). Five studies reported on MO and showed a reduced risk with NSAIDs, but we judged this evidence to be of low-certainty (RR 0.27, 95% CI 0.18 to 0.41; eyes = 520). Three studies reported BCVA at three months and the results of these trials were inconsistent, but all three studies found differences of less than 0.1 logMAR between groups.We did not note any major adverse events - the main consistent observation was burning or stinging sensation with the use of NSAIDs. AUTHORS' CONCLUSIONS: Using topical NSAIDs may reduce the risk of developing macular oedema after cataract surgery, although it is possible that current estimates as to the size of this reduction are exaggerated. It is unclear the extent to which this reduction has an impact on the visual function and quality of life of patients. There is little evidence to suggest any important effect on vision after surgery. The value of adding topical NSAIDs to steroids, or using them as an alternative to topical steroids, with a view to reducing the risk of poor visual outcome after cataract surgery is therefore uncertain. Future trials should address the remaining clinical uncertainty of whether prophylactic topical NSAIDs are of benefit, particularly with respect to longer-term follow-up (at least to 12 months), and should be large enough to detect reduction in the risk of the outcome of most interest to patients, which is chronic macular oedema leading to visual loss

A case of panuveitis with hypopyon due to presumed ocular leishmaniasis in a HIV patient.

BACKGROUND: Post-kala-azar dermal leishmaniasis is a well-known immunologic cutaneous reaction. There are few case reports of ocular leishmaniasis. It is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. Ocular leishmaniasis panuveitis can present with severe inflammation in patients with highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome. FINDINGS: A case of a 40-year-old man, human immunodeficiency virus (HIV) positive on HAART, with a presumed diagnosis of ocular leishmaniasis, is presented. He had a past history of visceral leishmaniasis and was referred to the uveitis service with rapidly worsening panuveitis and counting fingers vision in both eyes. On empirical anti-leishmania therapy and systemic steroids, the visual acuity of the left eye improved to 6/9 but remained poor in the right eye. Based on the medical history, improvement with therapy and the exclusion of other common infections, a presumed diagnosis of ocular leishmaniasis-related panuveitis was made. CONCLUSIONS: A major immune reaction against lingering parasites may play a key role in the pathogenesis of this sight-threatening and rapidly progressive condition. Both the infection and the immune reaction should be treated

Paraphrastic Reformulations in Spoken Corpora

International audienceOur work addresses the automatic detection of paraphrastic reformulation in French spoken corpora. The proposed approach is syn-tagmatic. It is based on specific markers and the specificities of the spoken language. Manual multi-dimensional annotation performed by two annotators provides fine-grained reference data. An automatic method is proposed in order to decide whether sentences contain or not paraphras-tic relations. The obtained results show up to 66.4% precision. Analysis of the manual annotations indicates that few paraphrastic segments show morphological modifications (inflection, derivation or compounding) and that the syntactic equivalence between the segments is seldom respected, as these usually belong to different syntactic categories

Microcoil Spring Interconnects for Ceramic Grid Array Integrated Circuits

As integrated circuit miniaturization trends continue, they drive the need for smaller higher input/output (I/O) packages. Hermetically sealed ceramic area array parts are the package of choice by the space community for high reliability space flight electronic hardware. Unfortunately, the coefficient of thermal expansion mismatch between the ceramic area array package and the epoxy glass printed wiring board limits the life of the interconnecting solder joint. This work presents the results of an investigation by Marshall Space Flight Center into a method to increase the life of this second level interconnection by the use of compliant microcoil springs. The design of the spring and its attachment process are presented along with thermal cycling results of microcoil springs (MCS) compared with state-of-the-art ball and column interconnections. Vibration testing has been conducted on MCS and high lead column parts. Radio frequency simulation and measurements have been made and the MCS has been modeled and a stress analysis performed. Thermal cycling and vibration testing have shown MCS interconnects to be significantly more reliable than solder columns. Also, MCS interconnects are less prone to handling damage than solder columns. Future work that includes shock testing, incorporation into a digital signal processor board, and process evaluation of expansion from a 400 I/O device to a device with over 1,100 I/O is identified

Environmental release, fate and ecotoxicological effects of manufactured ceria nanomaterials

Recent interest in the environmental fate and effects of manufactured CeO2 nanomaterials (nanoceria) has stemmed from its expanded use for a variety of applications including fuel additives, catalytic converters, chemical and mechanical planarization media and other uses. This has led to a wave of publications on the toxicological effects of nanoceria in ecological receptor species, but only limited information is available on possible environmental releases, concentrations in environmental media, or environmental transformations. In this paper, we make initial estimates of likely environmental releases and exposure concentrations in soils and water and compare them to published toxicity values. Insufficient information was available to estimate aquatic exposures, but we estimated inputs to a hypothetical wastewater treatment plant that could result in effluent concentrations that would result in acute toxicity to the most sensitive aquatic organisms tested so far, cyanobacteria. The purpose of this exercise is to identify which areas are lacking in data to perform either regional or site specific ecological risk assessments. While estimates can be made for releases from use as a diesel fuel additive, and predicted toxicity is low in most terrestrial species tested to date, estimates for releases from other uses are difficult at this stage. We recommend that future studies focus on environmentally realistic exposures that take into account potential environmental transformations of the nanoceria surface as well as chronic toxicity studies in benthic aquatic organisms, soil invertebrates and microorgansims

Advances in small lasers

M.T.H was supported by an Australian Research council Future Fellowship research grant for this work. M.C.G. is grateful to the Scottish Funding Council (via SUPA) for financial support.Small lasers have dimensions or modes sizes close to or smaller than the wavelength of emitted light. In recent years there has been significant progress towards reducing the size and improving the characteristics of these devices. This work has been led primarily by the innovative use of new materials and cavity designs. This Review summarizes some of the latest developments, particularly in metallic and plasmonic lasers, improvements in small dielectric lasers, and the emerging area of small bio-compatible or bio-derived lasers. We examine the different approaches employed to reduce size and how they result in significant differences in the final device, particularly between metal- and dielectric-cavity lasers. We also present potential applications for the various forms of small lasers, and indicate where further developments are required.PostprintPeer reviewe

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK092760)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK49216)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant U54DK110805)National Heart, Lung, and Blood Institute (Grant UO1-HL100001)National Heart, Lung, and Blood Institute (Grant U01HL134812)National Heart, Lung, and Blood Institute (Grant R01HL04880)National Institutes of Health (U.S.) (Grant R24OD017870-01

Reconfiguration, contestation, and decline: conceptualizing mature large technical systems

Large technical systems (LTS) are integral to modern lifestyles but arduous to analyze. In this paper, we advance a conceptualization of LTS using the notion of mature “phases,” drawing from insights into innovation studies, science and technology studies, political science, the sociology of infra- structure, history of technology, and governance. We begin by defining LTS as a unit of analysis and explaining its conceptual utility and novelty, situating it among other prominent sociotechnical theories. Next, we argue that after LTS have moved through the (overlapping) phases proposed by Thomas Hughes of invention, expansion, growth, momentum, and style,mature LTS undergo the additional (overlapping) phases of reconfiguration, contestation (subject to pressures such as drift and crisis), and eventually stagnation and decline. We illustrate these analytical phases with historical case studies and the conceptual literature, and close by suggesting future research to refine and develop the LTS framework, particularly related to more refined typologies, temporal dimensions, and a broadening of system users. We aim to contribute to theoretical debates about the coevolution of LTS as well as empirical discussions about system-related use, socio- technical change, and policy-making