Treatments for macular oedema following central retinal vein occlusion: systematic review

Objectives: To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).

Data sources: MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).

Study eligibility criteria, participants and interventions: RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.

Study appraisal and synthesis methods: 2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.

Results: 8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.

Limitations: All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.

Conclusions and implications of key findings: Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.

Anniversaries

The hundredth anniversary of the outbreak of the First World War is only the first of a large number of major European historical anniversaries that will occur in the coming four years. Other twentieth-century anniversaries include that of the Russian Revolution and the Easter Uprising; notable corollaries from earlier centuries include the Battle of Bannockburn, the Hanoverian succession, the Battle of Waterloo and, perhaps most significant of all, the five hundredth anniversary of the Lutheran Reformation. Rather than commission special issues or other features to tie in to individual anniversaries centred on or relevant to German history in a manner which repeats unthinkingly the conventions of scholarly and popular culture, the editors elected to reflect more fundamentally on what might be at stake in major anniversaries for professional scholars of history. In anticipation of the major wave of scholarly and popular publications, commemorative activities and memory conflicts that each of these will generate, and in order to reflect upon the dynamics of German history, memory and commemoration in a more overtly comparative context, the editors invited a number of scholars working on different national histories to reflect on the possibilities and potential pitfalls such anniversaries offer to historians who tie their work in to such moments. They are Jörg Arnold (Nottingham), Thomas A. Brady (Berkeley), Fearghal McGarry (Queen’s University, Belfast), Tim Grady (Chester) and Dan Healey (St Antony’s College, Oxford). The questions were posed by the editors.

The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties

There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings. © 2014 Federation of European Biochemical Societies.

Multi-Fidelity Multidisciplinary Whole Engine Thermo-Mechanical Design Optimization

Traditionally, the optimization of a turbomachinery engine casing for tip clearance has involved either twodimensional transient thermomechanical simulations or three-dimensional mechanical simulations. This paper illustrates that three-dimensional transient whole-engine thermomechanical simulations can be used within tip clearance optimizations and that the efficiency of such optimizations can be improved when a multifidelity surrogate modeling approach is employed. These simulations are employed in conjunction with a rotor suboptimization using surrogate models of rotor-dynamics performance, stress, mass and transient displacements, and an engine parameterization.

Biomass-derived Oxymethylene Ethers as Diesel Additives: A Thermodynamic Analysis

Conversion of biomass for production of liquid fuels can help in reducing the greenhouse gas (GHG) emissions which are predominantly generated by combustion of fossil fuels. Adding oxymethylene ethers (OMEs) in conventional diesel fuel has the potential to reduce soot formation during the combustion in a diesel engine. OMEs are downstream products of syngas, which can be generated by the gasification of biomass. In this research, a thermodynamic analysis has been conducted through development of data intensive process models of all the unit operations involved in production of OMEs from biomass. Based on the developed model, the key process parameters affecting the OMEs production including equivalence ratio, H2/CO ratio, and extra water flow rate were identified. This was followed by development of an optimal process design for high OMEs production. It was found that for a fluidized bed gasifier with heat capacity of 28 MW, the conditions for highest OMEs production are at an air amount of 317 tonne/day, at H2/CO ratio of 2.1, and without extra water injection. At this level, the total OMEs production is 55 tonne/day (13 tonne/day OME3 and 9 tonne/day OME4). This model would further be used in a techno-economic assessment study of the whole biomass conversion chain to determine the most attractive pathways.

Clinical trial designs for rare diseases: Studies developed and discussed by the International Rare Cancers Initiative

BACKGROUND: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.

SETTINGS: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional--usually randomized--clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.

RESULTS: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design.

INTERPRETATION: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases.

Composite hunting technologies from the Terminal Pleistocene and Early Holocene, Niah Cave, Borneo

Renewed archaeological investigation of the West Mouth of Niah Cave, Borneo has demonstrated that even within lowland equatorial environments depositional conditions do exist where organic remains of late glacial and early post-glacial age can be preserved. Excavations by the Niah Cave Research Project (NCP) (2000-2003) towards the rear of the archaeological reserve produced several bone points and worked stingray spines, which exhibit evidence of hafting mastic and fibrous binding still adhering to their shafts. The position of both gives strong indication of how these cartilaginous points were hafted and gives insight into their potential function. These artefacts were recovered from secure and (14)C dated stratigraphic horizons. The results of this study have implications for our understanding the function of the Terminal Pleistocene and Early Holocene bone tools recovered from other regions of Island Southeast Asia. They demonstrate that by the end the Pleistocene rainforest foragers in Borneo were producing composite technologies that probably included fishing leisters and potentially the bow and arrow. (C) 2009 Elsevier Ltd. All rights reserved.

The Climate of War: Violence, Warfare and Climatic Reductionism

National security agencies and other interested parties now often regard conflict as the inevitable consequence of climate change. This inclination to reduce war to the vicissitudes of climate is not new however. Here I examine some of the earlier ways in which violence was attributed to climatic conditions, particularly in the United States, and trace links between these older advocates of climatic determinism and the recent writings of those insisting that climate change will usher in a grim world of chronic warfare. It ends by drawing attention to the writings of some critics who are troubled by the ease with which climatic reductionism is capturing the public imagination.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

BACKGROUND: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

METHODS: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

RESULTS: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

CONCLUSION: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.

Biomass-derived oxymethylene ethers as diesel additives: A techno-economic assessment

Conversion of agricultural biomass such as wood chips, wheat straw and forest residue for the production of fuels can help in reducing GHG emissions since they are considered as nearly carbon neutral. Around the world there is a significant amount of forest and agricultural-biomass available which could be used for the production of liquid fuels that can be blended with the petroleum-based diesel. Oxymethylene ethers (OMEs) can be derived from biomass via gasification, water-gas shift reaction and methanol production. The addition of OMEs to conventional diesel fuel has great potential to reduce soot formation during the combustion in diesel engines. Unlike methanol and dimethyl ether (DMM) which can also reduce soot formation, the physical properties of OMEs allow the use in modern diesel engines without significant change of the engines infrastructure. In this study, a detailed and data intensive process simulation model was developed to simulate all the unit operations involved in the production of OMEs from biomass. The unit operation considered include biomass drying, gasification, gas cleaning, water gas shift reaction, methanol production and OMEs synthesis. The simulation results were then utilized to conduct a detailed techno-economic assessment study of the whole biomass conversion chain to determine the most attractive pathways for OMEs production. Our recent study shows that the key parameters affecting the OMEs production are equivalence ratio, H2/CO ratio and optimal air flow. Overall, the cost of production ($/liter) of OMEs from different biomass feedstock in Alberta will be determined