Risk factors for hospital re-presentation among older adults following fragility fractures: Protocol for a systematic review

Background After being discharged from hospital following the acute management of a fragility fracture, older adults may re-present to hospital emergency departments in the post-discharge period. Early re-presentation to hospital, which includes hospital readmissions, and emergency department presentations without admission, may be considered undesirable for individuals, hospital institutions and society. The identification of modifiable risk factors for hospital re-representation following initial fracture management may prove useful for informing policy or practice initiatives that seek to minimise the need for older adults to re-present to hospital early after they have been discharged from their initial inpatient care. The purpose of this systematic review is to identify correlates of hospital re-presentation in older patients who have been discharged from hospital following clinical management of fragility fractures. Methods/Design The review will follow the PRISMA-P reporting guidelines for systematic reviews. Four electronic databases (Pubmed, CINAHL, Embase, and Scopus) will be searched. A suite of search terms will identify peer-reviewed articles that have examined the correlates of hospital re-presentation in older adults (mean age of 65 years or older) who have been discharged from hospital following treatment for fragility fractures. The Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies will be used to assess the quality of the studies. The strength of evidence will be assessed through best evidence synthesis. Clinical and methodological heterogeneity across studies are likely to impede meta-analyses. Discussion The best evidence synthesis will outline correlates of hospital re-presentations in this clinical group. This synthesis will take into account potential risks of bias for each study, while permitting inclusion of findings from a range of quantitative study designs. It is anticipated that findings from the review will be useful in identifying potentially modifiable risk factors that have relevance in policy, practice and research priorities to improve the management of patients with fragility fractures. Systematic Review Registration PROSPERO CRD42015019379

fMRI evidence of word frequency and strength effects during episodic memory encoding

Word frequency (WF) and strength effects are two important phenomena associated with episodic memory. The former refers to the superior hit-rate (HR) for low (LF) compared to high frequency (HF) words in recognition memory, while the latter describes the incremental effect(s) upon HRs associated with repeating an item at study. Using the "subsequent memory" method with event-related fMRI, we tested the attention-at-encoding (AE) [M. Glanzer, J.K. Adams, The mirror effect in recognition memory: data and theory, J. Exp. Psychol.: Learn Mem. Cogn. 16 (1990) 5-16] explanation of the WF effect. In addition to investigating encoding strength, we addressed if study involves accessing prior representations of repeated items via the same mechanism as that at test [J.L. McClelland, M. Chappell, Familiarity breeds differentiation: a subjective-likelihood approach to the effects of experience in recognition memory, Psychol. Rev. 105 (1998) 724-760], entailing recollection [K.J. Malmberg, J.E. Holden, R.M. Shiffrin, Modeling the effects of repetitions, similarity, and normative word frequency on judgments of frequency and recognition memory, J. Exp. Psychol.: Learn Mem. Cogn. 30 (2004) 319-331] and whether less processing effort is entailed for encoding each repetition [M. Cary, L.M. Reder, A dual-process account of the list-length and strength-based mirror effects in recognition, J. Mem. Lang. 49 (2003) 231-248]. The increased BOLD responses observed in the left inferior prefrontal cortex (LIPC) for the WF effect provide support for an AE account. Less effort does appear to be required for encoding each repetition of an item, as reduced BOLD responses were observed in the LIPC and left lateral temporal cortex; both regions demonstrated increased responses in the conventional subsequent memory analysis. At test, a left lateral parietal BOLD response was observed for studied versus unstudied items, while only medial parietal activity was observed for repeated items at study, indicating that accessing prior representations at encoding does not necessarily occur via the same mechanism as that at test, and is unlikely to involve a conscious recall-like process such as recollection. This information may prove useful for constraining cognitive theories of episodic memory.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

Mauve: How one man invented the colour that changed the world

In an essay, "The Books of Last Things", Delia Falconer discusses the emergence of a new genre in publishing - microhistories. She cites a number of recent titles in non-fiction and fiction - Longitude, Cod, Tulips, Pushkin's Button, Nathaniel's Nutmeg, Zarafa, The Surgeon of Crowthorne, The Potato, The Perfect Storm. Delia Falconer observes of this tradition: "One has the sense, reading these books, of a surprising weight, of pleasant shock. In part, it is because we are looking at things which are generally present around us, but modestly out of sight and mind - historical nitty gritty like cod, potatoes, longitudinal clocks - which the authors have thrust suddenly, like a Biblical visitation of frogs or locusts, in our face. Things like spice and buttons and clocks are generally seen to enable history on the large scale, but are not often viewed as its worthy subjects. And by the same grand logic of history, more unusual phenomena like cabinets of curiosities or glass-making or farm lore or sailors' knots are simply odd blips on its radar screen, interesting footnotes. These new books, microhistories, reverse the usual order of history, which argues from the general to the particular, in order to prove its inevitable progress. They start from the footnotes. But by reversing the process, and walking through the back door of history, you don't necessarily end up at the front of the same house." Delia Falconer speculates about the reasons for the popularity of microhistories. She concludes: "I would like to think that reading them is not simply an exercise in nostalgia, but a challenge to the present". In Mauve, Simon Garfield provides a new way of thinking and writing about the history of intellectual property. Instead of providing a grand historical narrative of intellectual property, he tells the story of a particular invention, and its exploitation. Simon Garfield relates how English chemist William Perkin accidentally discovered a way to mass-produce colour mauve in a factory. Working on a treatment for malaria in his London home laboratory, Perkin failed to produce artificial quinine. Instead he created a dark oily sludge that turned silk a beautiful light purple. The colour was unique and became the most desirable shade in the fashion houses of Paris and London. ... The book Mauve will have a number of contemporary resonances for intellectual property lawyers and academics. Simon Garfield emphasizes the difficulties inherent in commercialising an invention and managing intellectual property. He investigates the uneasy collaboration between industry and science. Simon Garfield suggests that complaints about the efficacy of patent offices are perennial. He also highlights the problems faced by courts and law-makers in accommodating new technologies within the logic of patent law. In his elegant microhistory of the colour mauve, Simon Garfield confirms the conclusion of Brad Sherman and Lionel Bently that many aspects of modern intellectual property law can only be understood through an understanding of the past: "The image of intellectual property law that developed during the 19th century and the narrative of identity which this engendered played and continue to play an important role in the way we think about and understand intellectual property law".

Matters Arising: Role of HLA genes in familial spondyloarthropathy

Said-Nahal and colleagues report an intriguing finding of an association with HLA-DR4 independent of B27 in families with ankylosing spondylitis (AS),1 a finding highlighted by an accompanying editorial.2 The approach of studying B27 positive and B27 negative haplotypes may prove powerful in identifying further cis or trans encoded genes involved in AS. However, the reported association of DR4 with AS is quite a surprising finding given that no difference was noted in B27-DR4 haplotype frequencies in patients and ethnically matched healthy controls. Many previous studies have not reported any such association,3–9 including a similar preliminary study by the same authors.10 Although these studies were mainly case-control studies, population stratification is highly unlikely to cause a false negative finding if the effect size of the reported association with DR4 is as high as Said-Nahal and colleagues describe...

Introduction: Epitope mimicry as a component cause of autoimmune disease

The causes of autoimmune diseases have yet to be fully elucidated. Autoantibodies, autoreactive T cell responses, the presence of a predisposing major histocompatibility complex (MHC) haplotype and responsiveness to corticosteroids are features, and some are possibly contributory causes of autoimmune disease. The most challenging question is how autoimmune diseases are triggered. Molecular mimicry of host cell determinants by epitopes of infectious agents with ensuing cross-reactivity is one of the most popular yet still controversial theories for the initiation of autoimmune diseases [1]. Throughout the 1990s, hundreds of research articles focusing to various extents on epitope mimicry, as it is more accurately described in an immunological context, were published annually. Many of these articles presented data that were consistent with the hypothesis of mimicry but that did not actually prove the theory. Other equally convincing reports indicated that epitope mimicry was not the cause of the autoimmune disease despite sequence similarity between molecules of infectious agents and the host. Some 20 years ago, Rothman [2] proposed a model for disease causation and I have used this as a framework to examine the role of epitope mimicry in the development of autoimmune disease. The thesis of Rothman’s model is that an effect, in this instance autoimmune disease, arises as a result of a cause. In most cases, multiple-component causes contribute synergistically to yield the effect, and each of these components alone is insufficient as a cause. Logically, some component causes, such as the presence of a particular autoimmune response, are also necessary causes.

Rights and wrongs of Australian government asylum seeker policy

Worldwide, no fewer than 50 million people a year are now fleeing dangerous and often life threatening situations in their countries of origin (UNHCR, 2014c). As one part of this movement, thousands risk journeys through dangerous waters hoping to obtain asylum in Australia. However, Australian Government policies adopted since 2013 aim to ensure that no asylum seeker nor any of the 3,500 detainees held in offshore detention centres will ever be settled on the mainland. To this has now been added a declaration that none of the recent refugees or 6200 asylum seekers waiting in Indonesia in centres run by the United Nations High Commissioner for Refugees (UNHCR) will gain entry (Whyte, 2014a). These immigration policies differ dramatically from those adopted in earlier decades that produced the country’s decidedly multicultural identity. This article reviews these changing perspectives of Australian governments and communities within the context of international obligations and expectations; the experiences of those directly involved in border policing practices and in detention centres; and the attitudes of national media. Relations and conflicts among the interests of the different parties are discussed and the scope for less punitive responses to the plight of asylum seekers is examined. The authors then focus on alternative processes to better address the interests and objectives of legitimately interested parties by processes which successively examine, optimise and reconcile the concerns of each. In so doing, they aim to demonstrate that such methods of sequential problem solving can respond effectively to the multiple concerns of the many significant stakeholders involved in increasingly significant global issues, whereas recourse to such single-goal, top-down programs as are expressed in the government’s current determination to “Stop the boats” at all costs are unlikely to prove sustainable.

Mapping bound plasmon propagation on a nanoscale stripe waveguide using quantum dots: Influence of spacer layer thickness

In this paper we image the highly confined long range plasmons of a nanoscale metal stripe waveguide using quantum emitters. Plasmons were excited using a highly focused 633 nm laser beam and a specially designed grating structure to provide stronger incoupling to the desired mode. A homogeneous thin layer of quantum dots was used to image the near field intensity of the propagating plasmons on the waveguide. We observed that the photoluminescence is quenched when the QD to metal surface distance is less than 10 nm. The optimised spacer layer thickness for the stripe waveguides was found to be around 20 nm. Authors believe that the findings of this paper prove beneficial for the development of plasmonic devices utilising stripe waveguides.

A preference-based semantics for CTD reasoning

In [8] the authors developed a logical system based on the definition of a new non-classical connective ⊗ capturing the notion of reparative obligation. The system proved to be appropriate for handling well-known contrary-to-duty paradoxes but no model-theoretic semantics was presented. In this paper we fill the gap and define a suitable possible-world semantics for the system for which we can prove soundness and completeness. The semantics is a preference-based non-normal one extending and generalizing semantics for classical modal logics.

Educational interventions for preventing vascular catheter bloodstream infections in critical care: Evidence map, systematic review and economic evaluation

Background Bloodstream infections resulting from intravascular catheters (catheter-BSI) in critical care increase patients' length of stay, morbidity and mortality, and the management of these infections and their complications has been estimated to cost the NHS annually £19.1–36.2M. Catheter-BSI are thought to be largely preventable using educational interventions, but guidance as to which types of intervention might be most clinically effective is lacking. Objective To assess the effectiveness and cost-effectiveness of educational interventions for preventing catheter-BSI in critical care units in England. Data sources Sixteen electronic bibliographic databases – including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), NHS Economic Evaluation Database (NHS EED), EMBASE and The Cochrane Library databases – were searched from database inception to February 2011, with searches updated in March 2012. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify any additional references. Review methods References were screened independently by two reviewers using a priori selection criteria. A descriptive map was created to summarise the characteristics of relevant studies. Further selection criteria developed in consultation with the project Advisory Group were used to prioritise a subset of studies relevant to NHS practice and policy for systematic review. A decision-analytic economic model was developed to investigate the cost-effectiveness of educational interventions for preventing catheter-BSI. Results Seventy-four studies were included in the descriptive map, of which 24 were prioritised for systematic review. Studies have predominantly been conducted in the USA, using single-cohort before-and-after study designs. Diverse types of educational intervention appear effective at reducing the incidence density of catheter-BSI (risk ratios statistically significantly < 1.0), but single lectures were not effective. The economic model showed that implementing an educational intervention in critical care units in England would be cost-effective and potentially cost-saving, with incremental cost-effectiveness ratios under worst-case sensitivity analyses of < £5000/quality-adjusted life-year. Limitations Low-quality primary studies cannot definitively prove that the planned interventions were responsible for observed changes in catheter-BSI incidence. Poor reporting gave unclear estimates of risk of bias. Some model parameters were sourced from other locations owing to a lack of UK data. Conclusions Our results suggest that it would be cost-effective and may be cost-saving for the NHS to implement educational interventions in critical care units. However, more robust primary studies are needed to exclude the possible influence of secular trends on observed reductions in catheter-BSI.

Positive development and assessment

Purpose – There has been a tendency in sustainability science to be passive. The purpose of this paper is to introduce an alternative positive framework for a more active and direct approach to sustainable design and assessment that de-couples environmental impacts and economic growth. Design/methodology/approach – This paper deconstructs some systemic gaps that are critical to sustainability in built environment management processes and tools, and reframes negative “sustainable” decision making and assessment frameworks into their positive counterparts. In particular, it addresses the omission of ecology, design and ethics in development assessment. Findings – Development can be designed to provide ecological gains and surplus “eco-services,” but assessment tools and processes favor business-as-usual. Despite the tenacity of the dominant paradigm (DP) in sustainable development institutionalized by the Brundtland Report over 25 years ago, these omissions are easily corrected. Research limitations/implications – The limitation is that the author was unable to find exceptions to the omissions cited here in the extensive literature on urban planning and building assessment tools. However, exceptions prove the rule. The implication is that it is not too late for eco-positive retrofitting of cities to increase natural and social capital. The solutions are just as applicable in places like China and India as the USA, as they pay for themselves. Originality/value – Positive development (PD) is a fundamental paradigm shift that reverses the negative models, methods and metrics of the DP of sustainable development. This paper provides an example of how existing “negative” concepts and practices can be converted into positive ones through a PD prism. Through a new form of bio-physical design, development can be a sustainability solution.

The hardness of revising defeasible preferences

Non-monotonic reasoning typically deals with three kinds of knowledge. Facts are meant to describe immutable statements of the environment. Rules define relationships among elements. Lastly, an ordering among the rules, in the form of a superiority relation, establishes the relative strength of rules. To revise a non-monotonic theory, we can change either one of these three elements. We prove that the problem of revising a non-monotonic theory by only changing the superiority relation is a NP-complete problem.

Teacher Education for High Poverty Schools

This volume captures the innovative, theory-based, and grounded work being done by established scholars who are interrogating how teacher education can prepare teachers to work in challenging and diverse high-poverty settings. It offers articles from the US, Australia, Canada, the UK and Chile by some of the most significant scholars in the field. Internationally, research suggests that effective teachers for high poverty schools require deep theoretical understanding as well as the capacity to function across three well-substantiated areas: deep content knowledge, well-tuned pedagogical skills, and demonstrated attributes that prove their understanding and commitment to social justice. Schools in low socioeconomic communities need quality teachers most, however, they are often staffed by the least experienced and least prepared teachers. The chapters in this volume examine how pre-service teachers are taught to understand the social contexts of education. Drawing on the individual expertise of the authors, the topics covered include unpacking poverty for pre-service teachers, issues related to urban schooling as well as remote and regional area schooling.

A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ∼20 ng ml -1 and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml -1. Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16 705 asthmatics and 30 809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.

Tissue engineered humanized bone supports human hematopoiesis in vivo

Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.