Metal oxide nanoparticles as potential MRI contrast agents

Magnetic resonance imaging (MRI) is a common medical imaging modality that does not require the administration of radiopharmaceuticals, as it relies on the inherent nuclear spin of the protons in the tissues and organs. However, it lacks sensitivity in comparison to imaging techniques such as positron emission tomography (PET) and therefore changes at a cellular level are difficult to detect. To increase the level of information that can be obtained from MR images, contrast agents such as superparamagnetic iron oxide nanoparticles (SPIONs) or gadolinium based chelates can be used. Contrast agents work by making areas of the image where the agent is concentrated either lighter or darker; this is known as T₁ and T₂ relaxation respectively. Typically, gadolinium based chelates influence T₁ relaxation times, and SPION affect T₂ relaxation times of the hydrogen protons within the target organ or tissue. Recently, research has expanded from the use of chelated compounds with an increasing focus on improving and refining the properties of nanoparticles as contrast agents. The work described here focusses on the preparation of new cation and anion doped SPION-based contrast agents with improved imaging properties for MRI. Specifically, the following series of oxide nanoparticles were prepared: Fe₂−xDyxO₃, Fe₂−xGdxO₃, Gd₂−xMnxO₃, Gd₂−xFexO₃, Dy₂−xFexO₃ and Fe₂O₃−xF₂x. The nanoparticles were prepared via either co-precipitation or solid state reactions. Powder X-ray diffraction, ICP-AES, TEM, SEM, XPS, Mössbauer spectroscopy and magnetic measurements were performed to characterise the samples. The potential of selected samples to be developed into contrast agents was tested at the Royal Infirmary in Hull.The nanoparticles prepared in this work that show the most potential for improving T₁ relaxation rates at 3 T are the Gd₂−xMnxO₃ nanoparticle series. Of these Gd₁.₉₈Mn₀.₀₂O₃, Gd₁.₉₀Mn₀.₁₀O₃, Gd₁.₇₉Mn₀.₂₁O₃ nanoparticles in addition to Fe₁.₉₆Gd₀.₀₄O₃ nanoparticles also show potential for use at 11.7 T as T₁ contrast agents.Fe₁.₉₆Gd₀.₀₄O₃ and Fe₁.₉₉Dy₀.₀₁O₃ nanoparticles exhibited high T₂ relaxation rates at 11.7 T compared to those of prepared γ-Fe₂O₃ nanoparticles.Fe₂O₃−xF₂x nanoparticles exhibited high T₂ relaxation rates at both 3 T and 11.7 T compared against γ-Fe₂O₃ nanoparticles, showing their potential for use both at clinical and higher magnetic field strengths

The role of professional elites in healthcare governance:Exploring the work of the medical director

Medical leaders occupy a prominent position in healthcare policy in many countries, both in terms of the governance of quality and safety within healthcare organisations, and in broader system-wide governance. There is evidence that having doctors on hospital boards is associated with higher quality services. What is not known is how they have this effect. Analysing data collected from observations, interviews and documents from 15 healthcare providers in England (2014-2019), we elaborate the role of medical directors in healthcare governance as 'translation work', 'diplomatic work', and 'repair work'. Our study highlights the often enduring emotional effects of repeated structural changes to clinical services. It also contributes to theories of professional restratification, showing the work of medical directors as regional 'political elites', and as 'corporate elites' in publicly-funded healthcare systems

Advanced Care Planning at the End of Life for People with Dementia

In the UK is estimated at around 800,000 people, with 90, 000 people with dementia in Scotland. It’s forecast that by 2025, one in three people over the age of 60 will have dementia when they die. It is not always recognised that dementia is a progressive and life-limiting illness – perhaps because you can die of other things for example cardiovascular disease. However, as a result dementia hasn’t received the same level of attention or professional support as other life-limiting illnesses e.g. cancer. In response, a lot of policies – like the Scottish palliative care strategy want to get us talking about death and dying – but we need to get dementia included in those conversations. Dementia involves complex physical and psychological needs. Symptoms, rate of progression, and longevity are all specific to the individual, and can be unpredictable. People in the more advanced stages typically lose mobility, speech, and the ability to chew and swallow safely. One of the things which can characterise the end of life for people with dementia is that things can end up happening to them which they would not have wanted. We can call this treatment undignified – not the kind of ending they would have wanted involving unnecessary interventions. This is what people are seeking to avoid

Evaluation of HIV counseling and testing in ANC settings and adherence to short course antiretroviral prophylaxis for PMTCT in Francistown, Botswana

Worldwide, it is estimated that two million children are infected with HIV (USAID 2005). The vast majority of these infections are the result of mother-to-child transmission (MTCT) of the virus during pregnancy, labor, or breastfeeding. However, there are effective methods for prevention of mother-to-child transmission (PMTCT). Botswana is one of the first countries in the developing world with a national PMTCT program that uses an efficacious and complex regimen to reduce vertical transmission. At the time of this evaluation (August - December 2005), the standard of care for prevention of MTCT of HIV in Botswana included three-drug antiretroviral therapy for HIV-infected women with a CD4 count of 200 (300 mg AZT in the morning and 300 mg AZT in the evening); four weeks of AZT for their infants; single-dose maternal and infant nevirapine (NVP); and 12 months of free infant formula. Botswana's PMTCT program also provided routine HIV testing for all pregnant women during antenatal care (ANC) to identify HIV-positive women for prophylaxis or treatment. While programs often report the number of individuals beginning AZT and receiving nevirapine for PMTCT, effectiveness is dependent on the level of adherence of individuals to these regimens. To describe adherence of pregnant women to the current PMTCT regimen, the Horizons Program of the Population Council, in collaboration with the Centers for Disease Control and Prevention (CDC) and Premiere Personnel in Botswana, conducted an evaluation to describe HIV-related services provided to women during their pregnancies, document the content of post-test counseling sessions for HIV-positive pregnant women, whether HIV-positive women remembered what had been discussed, the extent of AZT adherence based on self-reports, and the operational successes and barriers to adherence to AZT for PMTCT

Sign and Image: Representations of Plants on the Warka Vase of Early Mesopotamia

The Warka Vase is an iconic artifact of Mesopotamia. In the absence of rigorous botanical study, the plants depicted on the lowest register are usually thought to be flax and grain. This analysis of the image identified as grain argues that its botanical characteristics, iconographical context and similarity to an archaic sign found in proto-writing demonstrates that it should be identified as a date palm sapling. It confirms the identification of flax. The correct identification of the plants furthers our understanding of possible symbolic continuities spanning the centuries that saw the codification of text as a representation of natural language

Writing themselves in 3: the third national study on the sexual health and wellbeing of same sex attracted and gender questioning young people

Executive Summary Introduction This is the third of the Writing Themselves In national reports which have been conducted six years apart since 1998. In 2010, a total of 3134 same sex attracted and gender questioning (SSAGQ) young people participated in Writing Themselves In 3 (WTi3), almost double the number in 2004 and more than four times that of 1998. The participants, who were aged between 14 and 21 years, came from all states and territories of Australia, from remote (2%), rural (18%) and urban (67%) areas and from a range of culturally and linguistically diverse (CALD) backgrounds. There were more young women (57%) than young men (41%) and a smaller group (3%) who were gender questioning (GQ). Sexual feelings In 2010, the complex interaction of sexual attraction, identity and behaviour was even more evident than in previous studies. Most young men were exclusively same sex attracted but half of the young women were attracted to both sexes and less than one third exclusively to the same sex. More than a third of young people realized their sexual difference before puberty and there were few gender differences in age of first realization. More young people felt positive about their same sex attraction than in 2004. As in 2004, young people who felt bad about their sexuality used homophobic beliefs to describe their reasons whereas those who felt good used resistant, affirming explanations. Sexual identity Most young men identified as gay/homosexual. Young women were more likely to identify as bisexual. Young women chose a greater range of identity terms to describe their sexuality

Optimal Constructions for Chain-based Cryptographic Enforcement of Information Flow Policies

The simple security property in an information flow policy can be enforced by encrypting data objects and distributing an appropriate secret to each user. A user derives a suitable decryption key from the secret and publicly available information. A chain-based enforcement scheme provides an alternative method of cryptographic enforcement that does not require any public information, the trade-off being that a user may require more than one secret. For a given information flow policy, there will be many different possible chain-based enforcement schemes. In this paper, we provide a polynomial-time algorithm for selecting a chain-based scheme which uses the minimum possible number of keys. We also compute the number of secrets that will be required and establish an upper bound on the number of secrets required by any user

On the acquisition of either and too

This paper presents an experimental investigation of how English-learning children acquire the additive discourse particles either and too. In the target grammar these items exhibit near-complementary distribution conditioned on the polarity of their host sentence. The path leading to that grammar appears to be rather intricate. We present comprehension data showing that for an extended period of time (3–5 ya) learners find both items acceptable in both polarity environments, exhibiting only a weak adult-like tendency of preferring either in negative and too in positive sentences. At 6 ya, their grammar appears categorical wrt. either in that they no longer tolerate it in positive sentences while still exhibiting only a weak dispreference for too in negative environments. These findings are even more striking in the context of production data. We find that child-directed speech is essentially categorical, providing unambiguous evidence for the adult grammar. Moreover, we find essentially categorical, adult-like use of either and too in child production from the earliest stage of development. These observations raise a number of challenges for theories of either and too and for approaches to learning focus particles more generally. Perhaps most strikingly, the protracted insensitivity of the learner's grammar to accumulation of unambiguous evidence constitutes a novel argument from the abundance of evidence for encapsulated learning

Structure of IL-22 Bound to Its High-Affinity IL-22R1 Chain

SummaryIL-22 is an IL-10 family cytokine that initiates innate immune responses against bacterial pathogens and contributes to immune disease. IL-22 biological activity is initiated by binding to a cell-surface complex composed of IL-22R1 and IL-10R2 receptor chains and further regulated by interactions with a soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). IL-22R1 also pairs with the IL-20R2 chain to induce IL-20 and IL-24 signaling. To define the molecular basis of these diverse interactions, we have determined the structure of the IL-22/sIL-22R1 complex. The structure, combined with homology modeling and surface plasmon resonance studies, defines the molecular basis for the distinct affinities and specificities of IL-22 and IL-10 receptor chains that regulate cellular targeting and signal transduction to elicit effective immune responses

Intervening early to prevent gang and youth violence: the role of primary schools.

This report explores the extent to which young children at risk of gang involvement or youth violence are supported through evidence-based early intervention, particularly within primary schools. It draws on qualitative interviews with schools, local government officials, police and voluntary sector organisations within the London boroughs of Lambeth and Wandsworth, and builds on earlier EIF research which indicates that risk factors for gang involvement and youth violence can be spotted as early as age seven. Our research paints a picture of primary school staff who know their children and local families well, and who go above and beyond to try to provide strong, positive role models and to support children’s emotional wellbeing. However, there is also a strong sense that some school staff are intensely frustrated and feel unsupported in their efforts to work with vulnerable children. Some staff expressed anger and sadness as they told us that they feel unable to change children’s outcomes in spite of their best efforts. The school staff and stakeholders we spoke to identified a range of concerns, including: • the lack of a clear or shared understanding of the level of risk within a school • a lack of clarity or confidence in identifying and accessing statutory and other services beyond the school walls • a limited awareness of the range and quality of external support that is available to schools, and little evaluation of the external support that is commissioned • the pressure on schools to focus on academic performance to the exclusion of children’s wellbeing, a challenge which is often exacerbated in schools located in areas where the risk of gang and youth violence is likely to be higher. Our recommendations concentrate on four areas: • improving the use of evidence in commissioning in-school support and programmes, including by providing improved information to schools and by calling on funders and commissioners at the national or regional level to make evidence-based decisions • increasing the emphasis on and time available for developing children’s social and emotional skills in primary schools, including by making PSHE compulsory in all schools and by requiring Ofsted to consider how well schools are supporting children’s wellbeing alongside the academic performance • improving the links between schools and the wider early help system in their area, so that school staff are clear about the options that are open to them and confident that referrals will result in support for children and families • examining how the police can most effectively work within primary schools to help prevent gang and youth violence. This report is the first output of a three-year project that will explore and support the testing of evidence-informed approaches to early intervention to prevent gang involvement and youth violence. We will be working with the local authorities, police, participating schools and providers in Lambeth and Wandsworth over the next two years, with a view to co-designing, implementing and testing new approaches to preventing gang and youth violence through effective early intervention