Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination.

Permanent damage to white matter tracts, comprising axons and myelinating oligodendrocytes, is an important component of brain injuries of the newborn that cause cerebral palsy and cognitive disabilities, as well as multiple sclerosis in adults. However, regulatory factors relevant in human developmental myelin disorders and in myelin regeneration are unclear. We found that AXIN2 was expressed in immature oligodendrocyte progenitor cells (OLPs) in white matter lesions of human newborns with neonatal hypoxic-ischemic and gliotic brain damage, as well as in active multiple sclerosis lesions in adults. Axin2 is a target of Wnt transcriptional activation that negatively feeds back on the pathway, promoting β-catenin degradation. We found that Axin2 function was essential for normal kinetics of remyelination. The small molecule inhibitor XAV939, which targets the enzymatic activity of tankyrase, acted to stabilize Axin2 levels in OLPs from brain and spinal cord and accelerated their differentiation and myelination after hypoxic and demyelinating injury. Together, these findings indicate that Axin2 is an essential regulator of remyelination and that it might serve as a pharmacological checkpoint in this process

Massive amplitudes on the Coulomb branch of N=4 SYM

We initiate a systematic study of amplitudes with massive external particles on the Coulomb-branch of N=4 super Yang Mills theory: 1) We propose that (multi-)soft-scalar limits of massless amplitudes at the origin of moduli space can be used to determine Coulomb-branch amplitudes to leading order in the mass. This is demonstrated in numerous examples. 2) We find compact explicit expressions for several towers of tree-level amplitudes, including scattering of two massive W-bosons with any number of positive helicity gluons, valid for all values of the mass. 3) We present the general structure of superamplitudes on the Coulomb branch. For example, the n-point "MHV-band" superamplitude is proportional to a Grassmann polynomial of mixed degree 4 to 12, which is uniquely determined by supersymmetry. We find explicit tree-level superamplitudes for this MHV band and for other simple sectors of the theory. 4) Dual conformal generators are constructed, and we explore the dual conformal properties of the simplest massive amplitudes. Our compact expressions for amplitudes and superamplitudes should be of both theoretical and phenomenological interest; in particular the tree-level results carry over to truncations of the theory with less supersymmetry.Comment: 29 pages, 1 figur

Sources of evidence in HIV/AIDS care: pilot study comparing family physicians and AIDS service organization staff

BACKGROUND: The improvement of the quality of the evidence used in treatment decision-making is especially important in the case of patients with complicated disease processes such as HIV/AIDS for which multiple treatment strategies exist with conflicting reports of efficacy. Little is known about the perceptions of distinct groups of health care workers regarding various sources of evidence and how these influence the clinical decision-making process. Our objective was to investigate how two groups of treatment information providers for people living with HIV/AIDS perceive the importance of various sources of treatment information. METHODS: Surveys were distributed to staff at two local AIDS service organizations and to family physicians at three community health centres treating people living with HIV/AIDS. Participants were asked to rate the importance of 10 different sources of evidence for HIV/AIDS treatment information on a 5-point Likert-type scale. Mean rating scores and relative rankings were compared. RESULTS: Findings suggest that a discordance exists between the two health information provider groups in terms of their perceptions of the various sources of evidence. Furthermore, AIDS service organization staff ranked health care professionals as the most important source of information whereas physicians deemed AIDS service organizations to be relatively unimportant. The two groups appear to share a common mistrust for information from pharmaceutical industries. CONCLUSIONS: Discordance exists between medical "experts" from different backgrounds relating to their perceptions of evidence. Further investigation is warranted in order to reveal any effects on the quality of treatment information and implications in the decision-making process. Possible effects on collaboration and working relationships also warrant further exploration

Effects of X-ray dose on rhizosphere studies using X-ray computed tomography

X-ray Computed Tomography (CT) is a non-destructive imaging technique originally designed for diagnostic medicine, which was adopted for rhizosphere and soil science applications in the early 1980s. X-ray CT enables researchers to simultaneously visualise and quantify the heterogeneous soil matrix of mineral grains, organic matter, air-filled pores and water-filled pores. Additionally, X-ray CT allows visualisation of plant roots in situ without the need for traditional invasive methods such as root washing. However, one routinely unreported aspect of X-ray CT is the potential effect of X-ray dose on the soil-borne microorganisms and plants in rhizosphere investigations. Here we aimed to i) highlight the need for more consistent reporting of X-ray CT parameters for dose to sample, ii) to provide an overview of previously reported impacts of X-rays on soil microorganisms and plant roots and iii) present new data investigating the response of plant roots and microbial communities to X-ray exposure. Fewer than 5% of the 126 publications included in the literature review contained sufficient information to calculate dose and only 2.4% of the publications explicitly state an estimate of dose received by each sample. We conducted a study involving rice roots growing in soil, observing no significant difference between the numbers of root tips, root volume and total root length in scanned versus unscanned samples. In parallel, a soil microbe experiment scanning samples over a total of 24 weeks observed no significant difference between the scanned and unscanned microbial biomass values. We conclude from the literature review and our own experiments that X-ray CT does not impact plant growth or soil microbial populations when employing a low level of dose (<30 Gy). However, the call for higher throughput X-ray CT means that doses that biological samples receive are likely to increase and thus should be closely monitored

Non-perturbative effects and the refined topological string

The partition function of ABJM theory on the three-sphere has non-perturbative corrections due to membrane instantons in the M-theory dual. We show that the full series of membrane instanton corrections is completely determined by the refined topological string on the Calabi-Yau manifold known as local P1xP1, in the Nekrasov-Shatashvili limit. Our result can be interpreted as a first-principles derivation of the full series of non-perturbative effects for the closed topological string on this Calabi-Yau background. Based on this, we make a proposal for the non-perturbative free energy of topological strings on general, local Calabi-Yau manifolds.Comment: 38 pages, 5 figure

Process evaluation of appreciative inquiry to translate pain management evidence into pediatric nursing practice

Background Appreciative inquiry (AI) is an innovative knowledge translation (KT) intervention that is compatible with the Promoting Action on Research in Health Services (PARiHS) framework. This study explored the innovative use of AI as a theoretically based KT intervention applied to a clinical issue in an inpatient pediatric care setting. The implementation of AI was explored in terms of its acceptability, fidelity, and feasibility as a KT intervention in pain management. Methods A mixed-methods case study design was used. The case was a surgical unit in a pediatric academic-affiliated hospital. The sample consisted of nurses in leadership positions and staff nurses interested in the study. Data on the AI intervention implementation were collected by digitally recording the AI sessions, maintaining logs, and conducting individual semistructured interviews. Data were analysed using qualitative and quantitative content analyses and descriptive statistics. Findings were triangulated in the discussion. Results Three nurse leaders and nine staff members participated in the study. Participants were generally satisfied with the intervention, which consisted of four 3-hour, interactive AI sessions delivered over two weeks to promote change based on positive examples of pain management in the unit and staff implementation of an action plan. The AI sessions were delivered with high fidelity and 11 of 12 participants attended all four sessions, where they developed an action plan to enhance evidence-based pain assessment documentation. Participants labeled AI a 'refreshing approach to change' because it was positive, democratic, and built on existing practices. Several barriers affected their implementation of the action plan, including a context of change overload, logistics, busyness, and a lack of organised follow-up. Conclusions Results of this case study supported the acceptability, fidelity, and feasibility of AI as a KT intervention in pain management. The AI intervention requires minor refinements (e.g., incorporating continued follow-up meetings) to enhance its clinical utility and sustainability. The implementation process and effectiveness of the modified AI intervention require evaluation in a larger multisite study

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

&lt;b&gt;Background&lt;/b&gt; Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt; The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

An Approach to Enhance the Conservation-Compatibility of Solar Energy Development

The rapid pace of climate change poses a major threat to biodiversity. Utility-scale renewable energy development (>1 MW capacity) is a key strategy to reduce greenhouse gas emissions, but development of those facilities also can have adverse effects on biodiversity. Here, we examine the synergy between renewable energy generation goals and those for biodiversity conservation in the 13 M ha Mojave Desert of the southwestern USA. We integrated spatial data on biodiversity conservation value, solar energy potential, and land surface slope angle (a key determinant of development feasibility) and found there to be sufficient area to meet renewable energy goals without developing on lands of relatively high conservation value. Indeed, we found nearly 200,000 ha of lower conservation value land below the most restrictive slope angle (<1%); that area could meet the state of California’s current 33% renewable energy goal 1.8 times over. We found over 740,000 ha below the highest slope angle (<5%) – an area that can meet California’s renewable energy goal seven times over. Our analysis also suggests that the supply of high quality habitat on private land may be insufficient to mitigate impacts from future solar projects, so enhancing public land management may need to be considered among the options to offset such impacts. Using the approach presented here, planners could reduce development impacts on areas of higher conservation value, and so reduce trade-offs between converting to a green energy economy and conserving biodiversity