Reliability-based design optimization strategies based on FORM: a review

In deterministic optimization, the uncertainties of the structural system (i.e. dimension, model, material, loads, etc) are not explicitly taken into account. Hence, resulting optimal solutions may lead to reduced reliability levels. The objective of reliability based design optimization (RBDO) is to optimize structures guaranteeing that a minimum level of reliability, chosen a priori by the designer, is maintained. Since reliability analysis using the First Order Reliability Method (FORM) is an optimization procedure itself, RBDO (in its classical version) is a double-loop strategy: the reliability analysis (inner loop) and the structural optimization (outer loop). The coupling of these two loops leads to very high computational costs. To reduce the computational burden of RBDO based on FORM, several authors propose decoupling the structural optimization and the reliability analysis. These procedures may be divided in two groups: (i) serial single loop methods and (ii) unilevel methods. The basic idea of serial single loop methods is to decouple the two loops and solve them sequentially, until some convergence criterion is achieved. On the other hand, uni-level methods employ different strategies to obtain a single loop of optimization to solve the RBDO problem. This paper presents a review of such RBDO strategies. A comparison of the performance (computational cost) of the main strategies is presented for several variants of two benchmark problems from the literature and for a structure modeled using the finite element method.

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Disruption of vitellogenin gene function in adult honeybees by intra-abdominal injection of double-stranded RNA

Abstract Background The ability to manipulate the genetic networks underlying the physiological and behavioural repertoires of the adult honeybee worker (Apis mellifera) is likely to deepen our understanding of issues such as learning and memory generation, ageing, and the regulatory anatomy of social systems in proximate as well as evolutionary terms. Here we assess two methods for probing gene function by RNA interference (RNAi) in adult honeybees. Results The vitellogenin gene was chosen as target because its expression is unlikely to have a phenotypic effect until the adult stage in bees. This allowed us to introduce dsRNA in preblastoderm eggs without affecting gene function during development. Of workers reared from eggs injected with dsRNA derived from a 504 bp stretch of the vitellogenin coding sequence, 15% had strongly reduced levels of vitellogenin mRNA. When dsRNA was introduced by intra-abdominal injection in newly emerged bees, almost all individuals (96 %) showed the mutant phenotype. An RNA-fragment with an apparent size similar to the template dsRNA was still present in this group after 15 days. Conclusion Injection of dsRNA in eggs at the preblastoderm stage seems to allow disruption of gene function in all developmental stages. To dissect gene function in the adult stage, the intra-abdominal injection technique seems superior to egg injection as it gives a much higher penetrance, it is much simpler, and it makes it possible to address genes that are also expressed in the embryonic, larval or pupal stages.