Trends in a tumultuous region: Middle East after the Arab Awakening

Two years after the start of the Arab uprisings, the Middle East remains as tumultuous as ever. Despite the uncertainty and flux, a number of emerging trends will influence the region in the post-revolutionary period and well into the future.The first trend is a marked uptick in sectarianism and sectarian violence. The second trend is a crisis within political Islam and a widening rift between secular and Islamist political forces. And the third trend is the gradual disengagement and declining influence of the US in the Middle East. This paper, by Lydia Khalil, looks at the road to revolution, the polarised politics of Islamists vs secularists, and sectarianism’s grip in the region. The events in Egypt and Syria illustrate the difficulties faced by policymakers around the world—options for intervention are limited. However, the international community continues to look for ways to encourage stability. Australia\u27s role is considered including its role on the United Nations Security Council, particularly when it comes to the Syrian crisis and dealing with Iran’s nuclear ambitions. Australia should do what it can to assist this desperate humanitarian situation and bolster the norm against chemical weapons use. It’s important to do so, not only as a reflection of Australian values, but also because Australia’s actions and involvements on the international stage in relation to Syria will also have an impact at home

Foreign fighters in Syria and Iraq: the day after

In this Lowy Institute Analysis, Research Fellow Dr Rodger Shanahan and Nonresident Fellow Lydia Khalil argue that an increasing number of foreign fighters are likely to leave Syria and Iraq in the coming months and years, especially after the collapse of Islamic State’s caliphate, exacerbating the terrorist threat faced by the international community. Shanahan and Khalil highlight both the scale and nature of the long-term security threat that the foreign fighter cohort will pose, and ways in which the international community can ameliorate the threat.  Key findings The length and intensity of the Syrian and Iraqi conflicts will mean that those foreign fighters who survive will likely be the most operationally experienced, lethally skilled and highly networked group of jihadis to date. It will be impossible to contain the outflow of foreign fighters given the multiplicity of options available to them, and they will not all follow the same pattern of activity post-conflict. Security agencies will face difficulties in determining the threat each fighter is likely to pose and in allocating resources to deal with these individuals. Given the nature of a globalised society, national approaches to this foreign fighter problem will be insufficient to address the issue. A coordinated global approach, with all the difficulties this entails, is the only effective way in which to contain the threat

A lifecycle cost-driven system dynamics approach for considering additive re-manufacturing or repair in aero-engine component design

Aero-engine component design decisions should consider re-manufacturing and/or repair strategies and their impact on lifecycle cost. Existing design approaches do not account for alternative production technologies such as the use of additive manufacturing in life extension processes. This paper presents a modeling and optimization methodology for examining the impact of design decisions in the early development stage on component lifecycle cost during the in-service phase while considering the potential use of additive manufacturing in life extension strategies. Specifically, a system dynamics model is developed to assess different end-of-life scenarios. Finally, an optimization problem is formulated and solved to minimize lifecycle cost with respect to design variables related to remanufacturing

Influence of patient rotational malpositioning on pelvic parameters assessed on lateral radiographs

Aim: To estimate the effect of patients' axial rotation (AR) during pelvic radiograph acquisition, on the reliability and validity of sagittal pelvic parameters. Materials and methods: Lateral digitally reconstructed radiographs (LDRRs) were obtained from the pelvic computed tomography (CT) scans of eight children and nine adults. Then, the AR of the pelvis was simulated and the corresponding LDRRs were reconstructed at 5°, 10°, 15°, and 20° of the AR. Pelvic parameters were measured digitally on each radiograph. Intra- and interobserver variability were evaluated at each AR position (three operators repeated the measurements three times each). The bias on each clinical parameter, in each AR position, was calculated relatively to the 0° position. Results: Interobserver variability increased similarly in children and adults with AR. It reached 4.4° for pelvic incidence and 4.7° for the sacral slope at 20° of AR. Biases on radiological parameters increased with AR and exceeded the acceptable threshold of errors when AR reached 10°. A linear regression was established (R2=0.834, p<0.0001) in order to estimate the AR of a patient on a lateral pelvic radiograph based on the measurement of the bifemoral distance normalized to the sagittal pelvic thickness. Conclusions: AR of patients during radiograph acquisition can be estimated in clinical practice, which would allow physicians to discard any radiographs where the calculated AR exceeded 10°

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Binding Modes of Peptidomimetics Designed to Inhibit STAT3

STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers. Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities. Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing dimerization of cancer target protein STAT3

Epidemiology of injuries from fire, heat and hot substances : global, regional and national morbidity and mortality estimates from the Global Burden of Disease 2017 study

Background Past research has shown how fires, heat and hot substances are important causes of health loss globally. Detailed estimates of the morbidity and mortality from these injuries could help drive preventative measures and improved access to care. Methods We used the Global Burden of Disease 2017 framework to produce three main results. First, we produced results on incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years from 1990 to 2017 for 195 countries and territories. Second, we analysed these results to measure mortality-to-incidence ratios by location. Third, we reported the measures above in terms of the cause of fire, heat and hot substances and the types of bodily injuries that result. Results Globally, there were 8 991 468 (7 481 218 to 10 740 897) new fire, heat and hot substance injuries in 2017 with 120 632 (101 630 to 129 383) deaths. At the global level, the age-standardised mortality caused by fire, heat and hot substances significantly declined from 1990 to 2017, but regionally there was variability in age-standardised incidence with some regions experiencing an increase (eg, Southern Latin America) and others experiencing a significant decrease (eg, High-income North America). Conclusions The incidence and mortality of injuries that result from fire, heat and hot substances affect every region of the world but are most concentrated in middle and lower income areas. More resources should be invested in measuring these injuries as well as in improving infrastructure, advancing safety measures and ensuring access to care.Peer reviewe

Abstracts from the NIHR INVOLVE Conference 2017

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Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements