Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial

Background
Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment.

Methods
From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607.

Findings
Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015–0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI –1·99 to –0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events.

Interpretation
Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment.

FE simulation and experimental tests of high-strength structural bolts under tension

Experimental tests have been completed for high-strength 8.8 bolts for studying their mechanical performance subjected to tensile loading. As observed from these tests, failure of structural bolts has been identified as in one of two ways: threads stripping and necking of the threaded portion of the bolt shank, which is possibly due to the degree of fit between internal and external threads. Following the experimental work, a numerical approach has been developed for demonstration of the tensile performance with proper consideration of tolerance class between bolts and nuts. The degree of fit between internal and external threads has been identified as a critical factor affecting failure mechanisms of high-strength structural bolts in tension, which is caused by the machining process. In addition, different constitutive material laws have been taken into account in the numerical simulation, demonstrating the entire failure mechanism for structural bolts with different tolerance classes in their threads. It is also observed that the bolt capacities are closely associated with their failure mechanisms.

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging.

The Transverse Crack Tension test revisited: An experimental and numerical study

Several problems arise when measuring the mode II interlaminar fracture toughness using a Transverse Crack Tension specimen; in particular, the fracture toughness depends on the geometry of the specimen and cannot be considered a material parameter. A preliminary experimental campaign was conducted on TCTs of different sizes but no fracture toughness was measured because the TCTs failed in an unacceptable way, invalidating the tests. A comprehensive numerical and experimental investigation is conducted to identify the main causes of this behaviour and a modification of the geometry of the specimen is proposed. It is believed that the obtained results represent a significant contribution in the understanding of the TCT test as a mode II characterization procedure and, at the same time, provide new guidelines to characterize the mode II crack propagation under tensile loads.