Non-targeted effects of ionising radiation-Implications for low dose risk

Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understandfng of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations. in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. (C) 2012 Elsevier B.V. All rights reserved.

Positron scattering and annihilation on noble-gas atoms

Positron scattering and annihilation on noble-gas atoms is studied ab initio using many-body theory methods for positron energies below the positronium formation threshold. We show that in this energy range, the many-body theory yields accurate numerical results and provides a near-complete understanding of the positron–noble-gas atom system. It accounts for positron-atom and electron-positron correlations, including the polarization of the atom by the positron and the nonperturbative effect of virtual positronium formation. These correlations have a large influence on the scattering dynamics and result in a strong enhancement of the annihilation rates compared to the independent-particle mean-field description. Computed elastic scattering cross sections are found to be in good agreement with recent experimental results and Kohn variational and convergent close-coupling calculations. The calculated values of the annihilation rate parameter Zeff (effective number of electrons participating in annihilation) rise steeply along the sequence of noble-gas atoms due to the increasing strength of the correlation effects, and agree well with experimental data.

Risk, Regulation and the Reintegration of Sexual Offenders

Media reporting of and public concern about sexual offending, particularly relating to children, affects and reflects political, policy and organisational responses to those convicted of such crimes. The development of regulatory policies on sexual offending has taken place within a highly emotive and overtly politicized public and policy discourse. This chapter charts the various ways in which the risks imagined or posed by sexual offenders have been conceptualised within public discourses and regulated and managed under the legislative and organisational ‘risk paradigm.’ Ultimately, it argues that risk-based responses to sexual offending are at best uncertain in their effects and at worst counterproductive, in that they often reduce the potential for successful reintegration. In seeking to look ‘beyond risk’, the chapter also explores the usefulness of restorative and related practices in supporting sex offender reintegration aimed at the primary and secondary levels of harm prevention.

Real-time temperature estimation for power MOSFETs considering thermal aging effects

This paper presents a novel real-time power-device temperature estimation method that monitors the power MOSFET's junction temperature shift arising from thermal aging effects and incorporates the updated electrothermal models of power modules into digital controllers. Currently, the real-time estimator is emerging as an important tool for active control of device junction temperature as well as online health monitoring for power electronic systems, but its thermal model fails to address the device's ongoing degradation. Because of a mismatch of coefficients of thermal expansion between layers of power devices, repetitive thermal cycling will cause cracks, voids, and even delamination within the device components, particularly in the solder and thermal grease layers. Consequently, the thermal resistance of power devices will increase, making it possible to use thermal resistance (and junction temperature) as key indicators for condition monitoring and control purposes. In this paper, the predicted device temperature via threshold voltage measurements is compared with the real-time estimated ones, and the difference is attributed to the aging of the device. The thermal models in digital controllers are frequently updated to correct the shift caused by thermal aging effects. Experimental results on three power MOSFETs confirm that the proposed methodologies are effective to incorporate the thermal aging effects in the power-device temperature estimator with good accuracy. The developed adaptive technologies can be applied to other power devices such as IGBTs and SiC MOSFETs, and have significant economic implications. 

Cross-age tutoring in kindergarten and elementary school settings: A systematic review and meta-analysis

This systematic review summarizes effects of peer tutoring delivered to children between 5 and 11 years old by non-professional tutors, such as classmates, older children and adult community peer volunteers. Inclusion criteria for the review included tutoring studies with a randomized controlled trial design, reliable measures of academic outcomes, and duration of at least 12 weeks. Searches of electronic databases, previous reviews, and contacts with researchers yielded 11,564 titles. After screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g = 0.18, 95% CI: 0.08, 0.27, N = 8251), decoding skills (g = 0.29, 95% CI: 0.13, 0.44, N = 7081), and reading comprehension (g = 0.11, 95% CI: 0.01, 0.21, N = 6945). No significant effects were detected for other reading sub-skills or for mathematics. The benefits to tutees of non-professional cross-age peer tutoring can be given a positive, but weak recommendation. Effect Sizes were modest and in the range −0.02 to 0.29. Questions regarding study limitations, lack of cost information, heterogeneity of effects, and the relatively small number of studies that have used a randomized controlled trial design means that the evidence base is not as strong as it could be. Subgroup analyses of included studies indicated that highly-structured reading programmes were of more benefit than those that were loosely-structured. Large-scale replication trials using factorial designs, reliable outcome measures, process evaluations and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional peer tutoring may be most effective.

Antimicrobial efficacy of tobramycin polymeric nanoparticles for Pseudomonas aeruginosa infections in cystic fibrosis: formulation, characterisation and functionalisation with dornase alfa (DNase).

Inhaled antibiotics, such as tobramycin, for the treatment of Pseudomonas aeruginosa pulmonary infections are associated with the increase in life expectancy seen in cystic fibrosis (CF) patients over recent years. However, the effectiveness of this aminoglycoside is still limited by its inability to penetrate the thick DNA-rich mucus in the lungs of these patients, leading to low antibiotic exposure to resident bacteria. In this study, we created novel polymeric nanoparticle (NP) delivery vehicles for tobramycin. Using isothermal titration calorimetry, we showed that tobramycin binds with alginate polymer and, by exploiting this interaction, optimised the production of tobramycin alginate/chitosan NPs. It was established that NP antimicrobial activity against P. aeruginosa PA01 was equivalent to unencapsulated tobramycin (minimum inhibitory concentration 0.625 mg/L). Galleria mellonella was employed as an in vivo model for P. aeruginosa infection. Survival rates of 90% were observed following injection of NPs, inferring low NP toxicity. After infection with P. aeruginosa, we showed that a lethal inoculum was effectively cleared by tobramycin NPs in a dose dependent manner. Crucially, a treatment with NPs prior to infection provided a longer window of antibiotic protection, doubling survival rates from 40% with free tobramycin to 80% with NP treatment. Tobramycin NPs were then functionalised with dornase alfa (recombinant human deoxyribonuclease I, DNase), demonstrating DNA degradation and improved NP penetration of CF sputum. Following incubation with CF sputum, tobramycin NPs both with and without DNase functionalisation, exhibited anti-pseudomonal effects. Overall, this work demonstrates the production of effective antimicrobial NPs, which may have clinical utility as mucus-penetrating tobramycin delivery vehicles, combining two widely used CF therapeutics into a single NP formulation. This nano-antibiotic represents a strategy to overcome the mucus barrier, increase local drug concentrations, avoid systemic adverse effects and improve outcomes for pulmonary infections in CF.

Islamic fundamentalism since 1945:2nd revised and expanded edition

Featuring a brand new examination of Islamic fundamentalism in the wake of the Arab Spring, this fully revised and updated second edition of Islamic Fundamentalism since 1945 analyzes the roots and emergence of Islamic movements in the modern world and the main thinkers that inspired them.

Providing a much-needed historical overview of a fast-changing socio-political landscape, the main facets of Islamic fundamentalism are put in a global context, with a thematic debate of issues such as:

- the effects of colonialism on Islam

- secularism and the Islamic reaction

- Islam and violence in the 9/11 era

- globalization and transnational Islamist movements

- Islam in the wake of the Arab Awakening

Islamic Fundamentalism since 1945 provides an authoritative account of the causes and diversity of Islamic fundamentalism, a modern phenomenon which has grabbed the headlines as a grave threat to the West and a potentially revolutionary trend in the Middle East. It is a valuable resource for students and those interested in the history, effects and consequences of these Islamic movements

Effect of nanosilica addition on the fresh properties and shrinkage of mortars with fly ash and superplasticizer

The ongoing use of various mineral additions along with chemical admixtures such as superplasticizers justifies the need for further research. Understanding and quantifying their effects and possible synergies on the fresh and hardened properties of cement-based materials is necessary, especially if some of these components are known to have a pozzolanic effect. This paper describes and models the fresh and hardened properties of cement mortars including nanosilica and fly ash, and relates their properties to the proportioning of these materials and the superplasticizer dosage. Mini-slump, Marsh cone and Lombardi cone tests were used to examine the properties of the fresh mortars, and to assess density, plastic shrinkage, and drying shrinkage up to 20 days. The equations presented in this paper make it possible to optimize mortar proportionings to the required levels of performance in both fresh and hardened states.

Nuclear disasters and health: lessons learned, challenges, and proposals

Past nuclear disasters, such as the atomic bombings in 1945 and major accidents at nuclear power plants, have highlighted similarities in potential public health effects of radiation in both circumstances, including health issues unrelated to radiation exposure. Although the rarity of nuclear disasters limits opportunities to undertake rigorous research of evidence-based interventions and strategies, identification of lessons learned and development of an effective plan to protect the public, minimise negative effects, and protect emergency workers from exposure to high-dose radiation is important. Additionally, research is needed to help decision makers to avoid premature deaths among patients already in hospitals and other vulnerable groups during evacuation. Since nuclear disasters can affect hundreds of thousands of people, a substantial number of people are at risk of physical and mental harm in each disaster. During the recovery period after a nuclear disaster, physicians might need to screen for psychological burdens and provide general physical and mental health care for many affected residents who might experience long-term displacement. Reliable communication of personalised risks has emerged as a challenge for health-care professionals beyond the need to explain radiation protection. To overcome difficulties of risk communication and provide decision aids to protect workers, vulnerable people, and residents after a nuclear disaster, physicians should receive training in nuclear disaster response. This training should include evidence-based interventions, support decisions to balance potential harms and benefits, and take account of scientific uncertainty in provision of community health care. An open and joint learning process is essential to prepare for, and minimise the effects of, future nuclear disasters.

Awareness and attitudes towards the emerging use of nanotechnology in the agri-food sector

Nanotechnology has relevance to applications in all areas of agri-food including agriculture, aquaculture, production, processing, packaging, safety and nutrition. Scientific literature indicates uncertainties in food safety aspects about using nanomaterials due to potential health risks. To date the agri-food industry's awareness and attitude towards nanotechnology have not been addressed. We surveyed the awareness and attitudes of agri-food organisations on the island of Ireland (IoI) with regards to nanotechnology. A total of 14 agri-food stakeholders were interviewed and 88 agri-food stakeholders responded to an on-line questionnaire. The findings indicate that the current awareness of nanotechnology applications in the agri-food sector on the IoI is low and respondents are neither positive nor negative towards agri-food applications of nanotechnology. Safer food, reduced waste and increased product shelf life were considered to be the most important benefits to the agri-food industry. Knowledge of practical examples of agri-food applications is limited however opportunities were identified in precision farming techniques, innovative packaging, functional ingredients and nutrition of foods, processing equipment, and safety testing. Perceived impediments to nanotechnology adoption were potential unknown human health and environmental impacts, consumer acceptance and media framing. The need for a risk assessment framework, research into long term health and environmental effects, and better engagement between scientists, government bodies, the agri-food industry and the public were identified as important.

Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes

BACKGROUND: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes.

METHODS: We performed GWAS of empirically derived positive and negative symptom scales in Irish cases from multiply affected pedigrees and a larger, independent case-control sample, subsequently combining these into a large Irish meta-analysis. In addition to single-SNP associations, we considered gene-based and pathway analyses to better capture convergent genetic effects, and to facilitate biological interpretation of these findings. Replication and testing of aggregate genetic effects was conducted using an independent European-American sample.

RESULTS: Though no single marker met the genome-wide significance threshold, genes and ontologies/pathways were significantly associated with negative and positive symptoms; notably, NKAIN2 and NRG1, respectively. We observed limited overlap in ontologies/pathways associated with different symptom profiles, with immune-related categories over-represented for negative symptoms, and addiction-related categories for positive symptoms. Replication analyses suggested that genes associated with clinical presentation are generalizable to non-Irish samples.

CONCLUSIONS: These findings strongly support the hypothesis that modifier loci contribute to the etiology of distinct Scz symptom profiles. The finding that previously implicated "risk loci" actually influence particular symptom dimensions has the potential to better delineate the roles of these genes in Scz etiology. Furthermore, the over-representation of distinct gene ontologies/pathways across symptom profiles suggests that the clinical heterogeneity of Scz is due in part to complex and diverse genetic factors.

The relationship between poverty, child abuse and neglect: an evidence review.

The review aimed to investigate two central issues.
1.To what extent is there evidence that poverty increases the amount of child abuse and neglect (CAN), and/or affects the nature of child abuse and neglect? How does this occur, how large are these effects and to whom do they apply?
2.To what extent is there evidence that CAN increases poverty later in life, how large are these effects and to whom do they apply?
Within these two issues evidence about equality and diversity, and cost were considered throughout.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.

METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.

RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).

CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Peer Effects in Adolescent Cannabis Use: It's the Friends, Stupid

This paper examines peer effects in adolescent cannabis use from several different reference groups, exploiting survey data that have many desirable properties and have not previously been used for this purpose. Treating the school grade as the reference group, and using both neighbourhood fixed effects and IV for identification, we find evidence of large, positive, and statistically significant peer effects. Treating nominated friends as the reference group, and using both school fixed effects and IV for identification, we again find evidence of large, positive, and generally statistically significant peer effects. Our preferred IV approach exploits information about friends of friends – ‘friends once removed’, who are not themselves friends – to instrument for friends’ cannabis use. Finally, we examine whether the cannabis use of schoolmates who are not nominated as friends – ‘non-friends’ – influences
own cannabis use. Once again using neighbourhood fixed effects and IV for identification, the evidence suggests zero impact. In our data, schoolmates who are not also friends have no influence on adolescent cannabis use.

Two-year changes in refractive error and related biometric factors in an adult Chinese population

Importance: This article provides, to our knowledge, the first longitudinal population-based data on refractive error (RE) in Chinese persons.

Objective: To study cohort effects and changes associated with aging in REs among Chinese adults.

Design, Setting, and Participants: A 2-year, longitudinal population-based cohort study was conducted in southern China. Participants, identified using cluster random sampling, included residents of Yuexiu District, Guangzhou, China, aged 35 years or older who had undergone no previous eye surgery.

Methods: Participants underwent noncycloplegic automated refraction and keratometry in December 2008 and December 2010; in a random 50% sample of the participants, anterior segment ocular coherence tomography measurement of lens thickness, as well as measurement of axial length and anterior chamber depth by partial coherence laser interferometry, were performed.

Main Outcomes and Measures: Two-year change in spherical equivalent refraction (RE), lens thickness, axial length, and anterior chamber depth in the right eye.

Results: A total of 745 individuals underwent biometric testing in both 2008 and 2010 (2008 mean [SD] age, 52.2 [11.5] years; 53.7% women). Mean RE showed a 2-year hyperopic shift from −0.44 (2.21) to −0.31 (2.26) diopters (D) (difference, +0.13; 95% CI, 0.11 to 0.16). A consistent 2-year hyperopic shift of 0.09 to 0.22 D was observed among participants aged 35 to 64 years when stratifying by decade, suggesting that a substantial change in RE with aging may occur during this 30-year period. Cross-sectionally, RE increased only in the cohort younger than 50 years (0.11 D/y; 95% CI, 0.06 to 0.16). In the cross-sectional data, axial length decreased at −0.06 mm/y (95% CI, −0.09 to −0.04), although the 2-year change in axial length was positive and thus could not explain the cross-sectional difference. These latter results suggest a cohort effect, with greater myopia developing among younger persons.

Conclusions and Relevance: This first Chinese population-based longitudinal study of RE provides evidence for both important longitudinal aging changes and cohort effects, most notably greater myopia prevalence among younger persons.