CPT Violation, Strings, and Neutral-Meson Systems

This talk provides a short overview of recent results on possible CPT violation and some associated experimental signatures.Comment: Presented at Orbis Scientiae, January 199

The Algorithmic Origins of Life

Although it has been notoriously difficult to pin down precisely what it is that makes life so distinctive and remarkable, there is general agreement that its informational aspect is one key property, perhaps the key property. The unique informational narrative of living systems suggests that life may be characterized by context-dependent causal influences, and in particular, that top-down (or downward) causation -- where higher-levels influence and constrain the dynamics of lower-levels in organizational hierarchies -- may be a major contributor to the hierarchal structure of living systems. Here we propose that the origin of life may correspond to a physical transition associated with a shift in causal structure, where information gains direct, and context-dependent causal efficacy over the matter it is instantiated in. Such a transition may be akin to more traditional physical transitions (e.g. thermodynamic phase transitions), with the crucial distinction that determining which phase (non-life or life) a given system is in requires dynamical information and therefore can only be inferred by identifying causal architecture. We discuss some potential novel research directions based on this hypothesis, including potential measures of such a transition that may be amenable to laboratory study, and how the proposed mechanism corresponds to the onset of the unique mode of (algorithmic) information processing characteristic of living systems.Comment: 13 pages, 1 tabl

An interferometric gravitational wave detector as a quantum-gravity apparatus

As a consequence of the extreme precision of the measurements it performs, an interferometric gravitational wave detector is a macroscopic apparatus for which quantum effects are not negligible. I observe that this property can be exploited to probe some aspects of the interplay between Quantum Mechanics and Gravity.Comment: LaTex, 7 pages. Version accepted for publication in Nature. Under press embargo until publicatio

Fundamental Strings, Holography, and Nonlinear Superconformal Algebras

We discuss aspects of holography in the AdS_3 \times S^p near string geometry of a collection of straight fundamental heterotic strings. We use anomalies and symmetries to determine general features of the dual CFT. The symmetries suggest the appearance of nonlinear superconformal algebras, and we show how these arise in the framework of holographic renormalization methods. The nonlinear algebras imply intricate formulas for the central charge, and we show that in the bulk these correspond to an infinite series of quantum gravity corrections. We also makes some comments on the worldsheet sigma-model for strings on AdS_3\times S^2, which is the holographic dual geometry of parallel heterotic strings in five dimensions.Comment: 25 page

The politics of the teaching of reading

Historically, political debates have broken out over how to teach reading in primary schools and infant classrooms. These debates and “reading wars” have often resulted from public concerns and media reportage of a fall in reading standards. They also reflect the importance placed on learning to read by parents, teachers, employers, and politicians. Public and media-driven controversies over the teaching of reading have resulted in intense public and professional debates over which specific methods and materials to use with beginning readers and with children who have reading difficulties. Recently, such debates have led to a renewed emphasis on reading proficiency and “standardized” approaches to teaching reading and engaging with literacy. The universal acceptance of the importance of learning to read has also led to vested interests in specific methods, reading programmes, and early literacy assessments amongst professional, business, commercial, and parental lobbying groups. This article traces these debates and the resulting growing support for a quantitative reductionist approach to early-reading programmes

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Stable isotope analysis provides new information on winter habitat use of declining avian migrants that is relevant to their conservation

Winter habitat use and the magnitude of migratory connectivity are important parameters when assessing drivers of the marked declines in avian migrants. Such information is unavailable for most species. We use a stable isotope approach to assess these factors for three declining African-Eurasian migrants whose winter ecology is poorly known: wood warbler Phylloscopus sibilatrix, house martin Delichon urbicum and common swift Apus apus. Spatially segregated breeding wood warbler populations (sampled across a 800 km transect), house martins and common swifts (sampled across a 3,500 km transect) exhibited statistically identical intra-specific carbon and nitrogen isotope ratios in winter grown feathers. Such patterns are compatible with a high degree of migratory connectivity, but could arise if species use isotopically similar resources at different locations. Wood warbler carbon isotope ratios are more depleted than typical for African-Eurasian migrants and are compatible with use of moist lowland forest. The very limited variance in these ratios indicates specialisation on isotopically restricted resources, which may drive the similarity in wood warbler populations' stable isotope ratios and increase susceptibility to environmental change within its wintering grounds. House martins were previously considered to primarily use moist montane forest during the winter, but this seems unlikely given the enriched nature of their carbon isotope ratios. House martins use a narrower isotopic range of resources than the common swift, indicative of increased specialisation or a relatively limited wintering range; both factors could increase house martins' vulnerability to environmental change. The marked variance in isotope ratios within each common swift population contributes to the lack of population specific signatures and indicates that the species is less vulnerable to environmental change in sub-Saharan Africa than our other focal species. Our findings demonstrate how stable isotope research can contribute to understanding avian migrants' winter ecology and conservation status

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt