Lessons from using iPads to understand young children's creativity

This paper explores how iPads can be used as part of a child-centred data collection approach to understanding young children’s creativity. Evidence is presented from a pilot study about 3- to 5-year-old children’s creative play. Researchers’ reflective accounts of children’s engagement with iPad video diaries and free to use apps were logged across two early educational settings over a three-month period. Findings suggest that iPads offer a mechanism to allow children to express their creative play and to encourage involvement in the research process. However, bespoke research software to use with early years children is required to improve this process

Exploring the affordances of smart toys and connected play in practice

What does children’s play look like in the smart toy era? What conceptual frameworks help make sense of the changing practices of children’s connected play worlds? Responding to these questions, this article re-frames discussions about children’s smart toy play within wider theoretical debates about the affordances of new digital materialities. To understand recent transformations of children’s play practices, we propose it is necessary to think of toys as increasingly media-like in their affordances and as connected to wider digital material ecosystems. To demonstrate the potential of this conceptual approach, we explore illustrative examples of two popular smart ‘care toys’. Our analysis identifies three examples of affordances that smart care toys share with other forms of mobile and robotic media: liveliness, affective stickiness and portability. We argue that locating discussions of smart toys within wider conceptual debates about digital materialities can provide new insights into the changing landscape of children’s play

The breadth of primary care: a systematic literature review of its core dimensions

Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level. Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit. Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health. Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health

Incentive payments are not related to expected health gain in the pay for performance scheme for UK primary care: cross-sectional analysis

Background: The General Medical Services primary care contract for the United Kingdom financially rewards performance in 19 clinical areas, through the Quality and Outcomes Framework. Little is known about how best to determine the size of financial incentives in pay for performance schemes. Our aim was to test the hypothesis that performance indicators with larger population health benefits receive larger financial incentives. Methods: We performed cross sectional analyses to quantify associations between the size of financial incentives and expected health gain in the 2004 and 2006 versions of the Quality and Outcomes Framework. We used non-parametric two-sided Spearman rank correlation tests. Health gain was measured in expected lives saved in one year and in quality adjusted life years. For each quality indicator in an average sized general practice we tested for associations first, between the marginal increase in payment and the health gain resulting from a one percent point improvement in performance and second, between total payment and the health gain at the performance threshold for maximum payment. Results: Evidence for lives saved or quality adjusted life years gained was found for 28 indicators accounting for 41% of the total incentive payments. No statistically significant associations were found between the expected health gain and incentive gained from a marginal 1% increase in performance in either the 2004 or 2006 version of the Quality and Outcomes Framework. In addition no associations were found between the size of financial payment for achievement of an indicator and the expected health gain at the performance threshold for maximum payment measured in lives saved or quality adjusted life years. Conclusions: In this subgroup of indicators the financial incentives were not aligned to maximise health gain. This disconnection between incentive and expected health gain risks supporting clinical activities that are only marginally effective, at the expense of more effective activities receiving lower incentives. When designing pay for performance programmes decisions about the size of the financial incentive attached to an indicator should be informed by information on the health gain to be expected from that indicator

Endoplasmic Reticulum Stress-Induced JNK Activation Is a Critical Event Leading to Mitochondria-Mediated Cell Death Caused by β-Lapachone Treatment

β-lapachone (β-lap) is a bioreductive agent that is activated by the two-electron reductase NAD(P)H quinone oxidoreductase 1 (NQO1). Although β-lap has been reported to induce apoptosis in various cancer types in an NQO1-dependent manner, the signaling pathways by which β-lap causes apoptosis are poorly understood.β-lap-induced apoptosis and related molecular signaling pathways in NQO1-negative and NQO1-overexpressing MDA-MB-231 cells were investigated. Pharmacological inhibitors or siRNAs against factors involved in β-lap-induced apoptosis were used to clarify the roles played by such factors in β-lap-activated apoptotic signaling pathways. β-lap leads to clonogenic cell death and apoptosis in an NQO1- dependent manner. Treatment of NQO1-overexpressing MDA-MB-231 cells with β-lap causes rapid disruption of mitochondrial membrane potential, nuclear translocation of AIF and Endo G from mitochondria, and subsequent caspase-independent apoptotic cell death. siRNAs targeting AIF and Endo G effectively attenuate β-lap-induced clonogenic and apoptotic cell death. Moreover, β-lap induces cleavage of Bax, which accumulates in mitochondria, coinciding with the observed changes in mitochondria membrane potential. Pretreatment with Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, efficiently attenuates JNK activation caused by β-lap, and subsequent mitochondria-mediated cell death. In addition, β-lap-induced generation and mitochondrial translocation of cleaved Bax are efficiently blocked by JNK inhibition.Our results indicate that β-lap triggers induction of endoplasmic reticulum (ER) stress, thereby leading to JNK activation and mitochondria-mediated apoptosis. The signaling pathways that we revealed in this study may significantly contribute to an improvement of NQO1-directed tumor therapies

Identification of Novel Avian Influenza Virus Derived CD8+ T-Cell Epitopes

Avian influenza virus (AIV) infection is a continuing threat to both humans and poultry. Influenza virus specific CD8+ T cells are associated with protection against homologous and heterologous influenza strains. In contrast to what has been described for humans and mice, knowledge on epitope-specific CD8+ T cells in chickens is limited. Therefore, we set out to identify AIV-specific CD8+ T-cell epitopes. Epitope predictions based on anchor residues resulted in 33 candidate epitopes. MHC I inbred chickens were infected with a low pathogenic AIV strain and sacrificed at 5, 7, 10 and 14 days post infection (dpi). Lymphocytes isolated from lung, spleen and blood were stimulated ex vivo with AIV-specific pooled or individual peptides and the production of IFNγ was determined by ELIspot. This resulted in the identification of 12 MHC B12-restricted, 3 B4-restricted and 1 B19-restricted AIV- specific CD8+ T-cell epitopes. In conclusion, we have identified novel AIV-derived CD8+ T-cell epitopes for several inbred chicken strains. This knowledge can be used to study the role of CD8+ T cells against AIV infection in a natural host for influenza, and may be important for vaccine development

Subcellular Min Oscillations as a Single-Cell Reporter of the Action of Polycations, Protamine, and Gentamicin on Escherichia coli

BACKGROUND: In Escherichia coli, MinD-GFP fusion proteins show rapid pole to pole oscillations. The objective was to investigate the effects of extracellular cations on the subcellular oscillation of cytoplasmic MinD within Escherichia coli. METHODOLOGY/PRINCIPAL FINDINGS: We exposed bacteria to the extracellular cations Ca(++), Mg(++), the cationic antimicrobial peptide (CAP) protamine, and the cationic aminoglycoside gentamicin. We found rapid and substantial increases in the average MinD oscillation periods in the presence of any of these polyvalent cations. For Ca(++) and Mg(++) the increases in period were transient, even with a constant extracellular concentration, while increases in period for protamine or gentamicin were apparently irreversible. We also found striking interdependence in the action of the small cations with protamine or gentamicin, distorted oscillations under the action of intermediate levels of gentamicin and Ca(++), and reversible freezing of the Min oscillation at high cationic concentrations. CONCLUSIONS/SIGNIFICANCE: Intracellular Min oscillations provide a fast single-cell reporter of bacterial response to extracellular polycations, which can be explained by the penetration of polycations into cells

Design of price incentives for adjunct policy goals in formula funding for hospitals and health services

Background. Hospital policy involves multiple objectives: efficiency of service delivery, pursuit of high quality care, promoting access. Funding policy based on hospital casemix has traditionally been considered to be only about promoting efficiency. Discussion. Formula-based funding policy can be (and has been) used to pursue a range of policy objectives, not only efficiency. These are termed 'adjunct' goals. Strategies to incorporate adjunct goals into funding design must, implicitly or explicitly, address key decision choices outlined in this paper. Summary. Policy must be clear and explicit about the behaviour to be rewarded; incentives must be designed so that all facilities with an opportunity to improve have an opportunity to benefit; the reward structure is stable and meaningful; and the funder monitors performance and gaming

Evolutionary Patterning: A Novel Approach to the Identification of Potential Drug Target Sites in Plasmodium falciparum

Malaria continues to be the most lethal protozoan disease of humans. Drug development programs exhibit a high attrition rate and parasite resistance to chemotherapeutic drugs exacerbates the problem. Strategies that limit the development of resistance and minimize host side-effects are therefore of major importance. In this study, a novel approach, termed evolutionary patterning (EP), was used to identify suitable drug target sites that would minimize the emergence of parasite resistance. EP uses the ratio of non-synonymous to synonymous substitutions (ω) to assess the patterns of evolutionary change at individual codons in a gene and to identify codons under the most intense purifying selection (ω≤0.1). The extreme evolutionary pressure to maintain these residues implies that resistance mutations are highly unlikely to develop, which makes them attractive chemotherapeutic targets. Method validation included a demonstration that none of the residues providing pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase enzyme were under extreme purifying selection. To illustrate the EP approach, the putative P. falciparum glycerol kinase (PfGK) was used as an example. The gene was cloned and the recombinant protein was active in vitro, verifying the database annotation. Parasite and human GK gene sequences were analyzed separately as part of protozoan and metazoan clades, respectively, and key differences in the evolutionary patterns of the two molecules were identified. Potential drug target sites containing residues under extreme evolutionary constraints were selected. Structural modeling was used to evaluate the functional importance and drug accessibility of these sites, which narrowed down the number of candidates. The strategy of evolutionary patterning and refinement with structural modeling addresses the problem of targeting sites to minimize the development of drug resistance. This represents a significant advance for drug discovery programs in malaria and other infectious diseases