United Kingdom: Citizenship education in the United Kingdom: comparing England, Northern Ireland, Scotland and Wales

Purpose: In this country case study the authors undertake a comparative analysis of citizenship education across the four nations of the UK. The curriculum and contexts in England, Scotland, Wales and Northern Ireland are first described. Then the article considers how each national example engages with fundamental expectations of citizenship education, specifically in relation to questions of citizenship status and the relationship between citizens and the state; political identity; and active citizenship processes. Approach: Drawing on the authors’ collective experience and insights into policy and practice in each nation, we started with a ‘generative conversation’ to identify key issues for inclusion in this case study. Findings: The article unearths a variety of constraints and problems, and situates these in a broader policyscape in which policy accretion and policy approximation generate a permissive culture, which has undermined the promise of citizenship education as an entitlement for all young people

Increased incidence of breast cancer in postmenopausal women with high body mass index at the modena screening program

Purpose: We conducted a study to evaluate the relationship between body mass index (BMI) and the risk of breast cancer (BC) and outcome in a population of 14,684 women aged 55 to 69 years eligible to participate in the Mammography Screening Program (MSP) in the Province of Modena, Italy. Methods: The study population was drawn from women who underwent mammography screening between 2004 and 2006 in the Province of Modena. Women were subdivided into obese, overweight, and normal-weight categories according to BMI and followed until July 31, 2010, to evaluate the BC incidence. The clinicopathological characteristics of BC were also evaluated in different groups of patients classified according to BMI. After BC diagnosis, patients were followed for a median period of 65 (range, 2\u2013104) months. Second events (recurrences and second tumors) were recorded, and the 5-year event-free survival (EFS) was calculated. Results: After a period of 73 months, 366 cases of BC were diagnosed. Compared with normal-weight women, obese women had a significantly higher incidence of BC (relative risk [RR], 1.32; p= 0.040) (RR=1), larger tumors (27% of tumors were larger than T2 size), and more nodal involvement (38.5% of tumors were node-positive). Furthermore, a significantly higher rate of total events was seen in obese women compared with overweight and normal-weight patients, respectively (17.9% vs. 11.4% vs. 10.8%, p=0.032). The 5-year EFS was 89.0%, 89.0%, and 80.0% for normal-weight, overweight, and obese patients, respectively. Conclusion: We observed a significantly higher risk of BC in obese women among those eligible to participate in the MSP in the Province of Modena. Finally, obese women had more second events and poorer EFS compared to nono bese women

Self-assembled hydrogel fiber bundles from oppositely charged polyelectrolytes mimic micro-/nanoscale hierarchy of collagen

Fiber bundles are present in many tissues throughout the body. In most cases, collagen subunits spontaneously self-assemble into a fibrilar structure that provides ductility to bone and constitutes the basis of muscle contraction. Translating these natural architectural features into a biomimetic scaffold still remains a great challenge. Here, a simple strategy is proposed to engineer biomimetic fiber bundles that replicate the self-assembly and hierarchy of natural collagen fibers. The electrostatic interaction of methacrylated gellan gum with a countercharged chitosan polymer leads to the complexation of the polyelectrolytes. When directed through a polydimethylsiloxane channel, the polyelectrolytes form a hierarchical fibrous hydrogel demonstrating nanoscale periodic light/dark bands similar to D-periodic bands in native collagen and align parallel fibrils at microscale. Importantly, collagen-mimicking hydrogel fibers exhibit robust mechanical properties (MPa scale) at a single fiber bundle level and enable encapsulation of cells inside the fibers under cell-friendly mild conditions. Presence of carboxyl- (in gellan gum) or amino- (in chitosan) functionalities further enables controlled peptide functionalization such as Arginylglycylaspartic acid (RGD) for biochemical mimicry (cell adhesion sites) of native collagen. This biomimetic-aligned fibrous hydrogel system can potentially be used as a scaffold for tissue engineering as well as a drug/gene delivery vehicle.S.S. and D.F.C. contributed equally to the work. This research was funded by the US Army Engineer Research and Development Center, the Institute for Soldier Nanotechnology, the NIH (HL092836, EB007249), and the National Science Foundation CAREER award (A.K.). This work was in part supported by FCT through funds from the POCTI and/or FEDER programs and from the European Union under the project NoE EXPERTISSUES (NMP3-CT-2004-500283). D.F.C. acknowledges the Foundation for Science and Technology (FCT), Portugal and the MIT-Portugal Program for personal grant SFRH/BD/37156/2007. S.S. acknowledges the postdoctoral fellowship awarded by Le Fonds Quebecois de la Recherche sur la Nature et les Technologies (FQRNT), Quebec, Canada and interdisciplinary training fellowship (NIH NRSA T32) awarded by System-based Consortium for Organ Design and Engineering (SysCODE). The authors would like to thank Dr. Iva Pashkuleva and Dr. Maria Ericsson for scientific discussions and technical assistance with TEM, respectivelyinfo:eu-repo/semantics/publishedVersio

The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Redox Biology 13 (2017): 207–218, doi:10.1016/j.redox.2017.05.023.Redox signaling is important for embryogenesis, guiding pathways that govern processes crucial for embryo patterning, including cell polarization, proliferation, and apoptosis. Exposure to pro-oxidants during this period can be deleterious, resulting in altered physiology, teratogenesis, later-life diseases, or lethality. We previously reported that the glutathione antioxidant defense system becomes increasingly robust, including a doubling of total glutathione and dynamic shifts in the glutathione redox potential at specific stages during embryonic development in the zebrafish, Danio rerio. However, the mechanisms underlying these changes are unclear, as is the effectiveness of the glutathione system in ameliorating oxidative insults to the embryo at different stages. Here, we examine how the glutathione system responds to the model pro-oxidants tert-butylhydroperoxide and tert-butylhydroquinone at different developmental stages, and the role of Nuclear factor erythroid 2-related factor (Nrf) proteins in regulating developmental glutathione redox status. Embryos became increasingly sensitive to pro-oxidants after 72 h post-fertilization (hpf), after which the duration of the recovery period for the glutathione redox potential was increased. To determine whether the doubling of glutathione or the dynamic changes in glutathione redox potential are mediated by zebrafish paralogs of Nrf transcription factors, morpholino oligonucleotides were used to knock down translation of Nrf1 and Nrf2 (nrf1a, nrf1b, nrf2a, nrf2b). Knockdown of Nrf1a or Nrf1b perturbed glutathione redox state until 72 hpf. Knockdown of Nrf2 paralogs also perturbed glutathione redox state but did not significantly affect the response of glutathione to pro-oxidants. Nrf1b morphants had decreased gene expression of glutathione synthesis enzymes, while hsp70 increased in Nrf2b morphants. This work demonstrates that despite having a more robust glutathione system, embryos become more sensitive to oxidative stress later in development, and that neither Nrf1 nor Nrf2 alone appear to be essential for the response and recovery of glutathione to oxidative insults.This research was supported by several NIH grants, including F32ES028085 (to KES), F32ES017585 (to ART-L), F32ES019832 (to LMW), P20GM103423 (to LMW), R01ES025748 (to ART-L), R01ES015912 (JJS), and R01ES016366 (MEH). Additional research support was provided by the J. Seward Johnson Fund at WHOI and the WHOI Postdoctoral Scholar Award with funding from Walter A. and Hope Noyes Smith (to ART-L)

Public awareness of cancer in Britain: a population-based survey of adults

*_Objective:_* To assess public awareness of cancer warning signs, anticipated delay, and perceived barriers to seeking medical advice in the British population. 
Methods: We carried out a population-based survey using face-to-face, computer-assisted interviews to administer the Cancer Awareness Measure (CAM), a newly-developed, validated measure of cancer awareness. The sample included 2216 adults (970 male and 1246 female) recruited as part of the Office for National Statistics Opinions Survey using stratified probability sampling.

*_Results:_* Awareness of cancer warning signs was low when open-ended (recall) questions were used and higher with closed (recognition) questions; but on either measure, awareness was lower in those who were male, younger, and from lower socioeconomic status (SES) groups or ethnic minorities. The most commonly endorsed barriers to help-seeking were difficulty making an appointment, worry about wasting the doctor’s time and worry about what would be found. Emotional barriers were more prominent in lower SES groups and practical barriers (e.g. too busy) more prominent in higher SES groups. Anticipated delay was lower in ethnic minority and lower SES groups. In multivariate analysis, higher symptom awareness was associated with lower anticipated delay, and more barriers with greater anticipated delay.

*_Conclusions:_* A combination of public education about symptoms and empowerment to seek medical advice, as well as support at primary care level, could enhance early presentation and improve cancer outcomes

The role of primary care in cancer diagnosis via emergency presentation: qualitative synthesis of significant event reports

Background: Patients diagnosed with cancer in the context of an emergency presentation (EP) have poorer outcomes. It is often assumed that such patients present to the emergency department without consulting their general practitioner (GP). Little work has been done to identify primary care involvement before hospital attendance. Methods: Participating primary care practices completed a significant event audit (SEA) report for the last patient diagnosed with cancer as a result of an EP. Accounts were synthesised and a qualitative approach to analysis undertaken. Results: SEAs for 222 patients were analysed. A range of cancers were included, the most common being lung (32.4%) and upper gastrointestinal (19.8%). In most cases, patients had contact with their practice before diagnosis, primarily in the period immediately before admission. In only eight cases had there been no input from primary care. Accounts of protracted primary care contact generally demonstrated complexity, often related to comorbidity, patient-mediated factors or reassurance provided by negative investigations. Learning points identified by practices centred on the themes of presentation and diagnosis, consultation and safety-netting, communication and system issues, patient factors and referral guidelines. Conclusions: There is extensive primary care input into patients whose diagnosis results from EP, and for the most part potential ‘delay’ in referral can be reasonably explained by the complexity of the presentation or by coexisting patient factors

Prognostic value of morphology and hormone receptor status in breast cancer - a population based study

We analysed the 5-year relative survival among 4473 breast cancer cases diagnosed in 1990-1992 from cancer registries in Estonia, France, Italy, Spain, the Netherlands and the UK. Among eight categories based on ICD-O codes (infiltrating ductal carcinoma, lobular plus mixed carcinoma, comedocarcinoma, 'special types', medullary carcinoma, not otherwise specified (NOS) carcinoma, other carcinoma and cancer without microscopic confirmation), the 5-year relative survival ranged from 66% (95% CI 61-71) for NOS carcinoma to 95% (95% CI 90-100) for special types (tubular, apocrine, cribriform, papillary, mucinous and signet ring cell); 27% (95% CI 18-36) for cases without microscopic confirmation. Differences in 5-year relative survival by tumor morphology and hormone receptor status were modelled using a multiple regression approach based on generalised linear models. Morphology and hormone receptor status were confirmed as significant survival predictors in this population-based study, even after adjusting for age and stage at diagnosis

The clinical drug candidate anle138b binds in a cavity of lipidic alpha-synuclein fibrils

Aggregation of amyloidogenic proteins is a characteristic of multiple neuro- degenerative diseases. Atomic resolution of small molecule binding to such pathological protein aggregates is of interest for the development of ther- apeutics and diagnostics. Here we investigate the interaction between α- synuclein fibrils and anle138b, a clinical drug candidate for disease modifying therapy in neurodegeneration and a promising scaffold for positron emission tomography tracer design. We used nuclear magnetic resonance spectroscopy and the cryogenic electron microscopy structure of α-synuclein fibrils grown in the presence of lipids to locate anle138b within a cavity formed between two β-strands. We explored and quantified multiple binding modes of the com- pound in detail using molecular dynamics simulations. Our results reveal stable polar interactions between anle138b and backbone moieties inside the tubular cavity of the fibrils. Such cavities are common in other fibril structures as well

Effect of an 860-m thick, cold, freshwater aquifer on geothermal potential along the axis of the eastern Snake River Plain, Idaho

A 1912-m exploration corehole was drilled along the axis of the eastern Snake River Plain, Idaho. Two temperature logs run on the corehole display an obvious inflection point at about 960 m. Such behavior is indicative of downward fluid flow in the wellbore. The geothermal gradient above 935 m is 4.5 °C/km, while the gradient is 72–75 °C/km from 980 to 1440 m. Projecting the higher gradients upward to where they intersect the lower gradient on the temperature logs places the bottom of the cold, freshwater Snake River Plain aquifer, which suppresses the geothermal gradient at this location, at least 860 m below the surface. The average heat flow for the corehole between 983 and 1550 m is 132 mW/m2. Although the maximum bottom-hole temperature extrapolated from a measured time–temperature curve was only 59.3 °C, geothermometers suggest an equilibrium temperature on the order of 125–140 °C based on a single fluid sample from 1070 m. Furthermore, below 960 m the basalt core shows obvious signs of alteration, including a distinct color change, the formation of smectite clay, and the presence of secondary minerals filling vesicles and fracture zones. This alteration boundary could act as an effective cap or seal for a hot-water geothermal system

Development of the systems thinking for health actions framework: a literature review and a case study

BACKGROUND: Systems thinking is an approach that views systems with a holistic lens, focusing on how components of systems are interconnected. Specifically, the application of systems thinking has proven to be beneficial when applied to health systems. Although there is plenty of theory surrounding systems thinking, there is a gap between the theoretical use of systems thinking and its actual application to tackle health challenges. This study aimed to create a framework to expose systems thinking characteristics in the design and implementation of actions to improve health. METHODS: A systematised literature review was conducted and a Taxonomy of Systems Thinking Objectives was adapted to develop the new 'Systems Thinking for Health Actions' (STHA) framework. The applicability of the framework was tested using the COVID-19 response in Pakistan as a case study. RESULTS: The framework identifies six key characteristics of systems thinking: (1) recognising and understanding interconnections and system structure, (2) identifying and understanding feedback, (3) identifying leverage points, (4) understanding dynamic behaviour, (5) using mental models to suggest possible solutions to a problem and (6) creating simulation models to test policies. The STHA framework proved beneficial in identifying systems thinking characteristics in the COVID-19 national health response in Pakistan. CONCLUSION: The proposed framework can provide support for those aiming to applying systems thinking while developing and implementing health actions. We also envision this framework as a retrospective tool that can help assess if systems thinking was applied in health actions