Cosmological particle creation in states of low energy

The recently proposed states of low energy provide a well-motivated class of reference states for the quantized linear scalar field on cosmological Friedmann-Robertson-Walker spacetimes. The low energy property of a state is localized close to some value of the cosmological time coordinate. We present calculations of the relative cosmological particle production between a state of low energy at early time and another such state at later time. In an exponentially expanding Universe, we find that the particle production shows oscillations in the spatial frequency modes. The basis of the method for calculating the relative particle production is completely rigorous. Approximations are only used at the level of numerical calculation.Comment: 24 pages, 7 figure

Asking questions can help: development and preliminary evaluation of a question prompt list for palliative care patients

Question prompt lists (QPLs) have been shown to be an inexpensive and effective communication tool for patients in oncology consultations. We aimed to develop and pilot a QPL for palliative care (PC) patients. In order to identify suitable questions for inclusion in the QPL, we conducted focus groups and individual interviews with 19 patients, 24 carers and 22 PC health professionals. A further 21 health professionals reviewed the draft document. The draft QPL was piloted in 23 patients. In total, 112 questions were identified and grouped into eight categories. All participants felt that the QPL, in booklet form, could be a useful tool. Out of 23 patients in the pilot study, 22 agreed that the QPL was helpful, contained useful questions, was easy to understand and would be useful in the future. State anxiety (STAI) decreased after receiving the booklet and seeing the doctor in 16 out of 19 patients (overall anxiety decreased by a median of 8, IQR 1-13). Participants in the pilot study endorsed the inclusion of end-of-life issues in the QPL, despite some reservations expressed about this by health professionals in the individual interviews. We have identified a specific QPL that might facilitate useful dialogue between PC patients and their doctor. The QPL has strong support from patients, their carers and relevant health professionals

On the spin-statistics connection in curved spacetimes

The connection between spin and statistics is examined in the context of locally covariant quantum field theory. A generalization is proposed in which locally covariant theories are defined as functors from a category of framed spacetimes to a category of $*$-algebras. This allows for a more operational description of theories with spin, and for the derivation of a more general version of the spin-statistics connection in curved spacetimes than previously available. The proof involves a "rigidity argument" that is also applied in the standard setting of locally covariant quantum field theory to show how properties such as Einstein causality can be transferred from Minkowski spacetime to general curved spacetimes.Comment: 17pp. Contribution to the proceedings of the conference "Quantum Mathematical Physics" (Regensburg, October 2014

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits

Group evaluations as self-group distancing:Ingroup typicality moderates evaluative intergroup bias in stigmatized groups

Outgroup favoritism among members of stigmatized groups can be seen as a form of self-group distancing. We examined how intergroup evaluations in stigmatized groups vary as a function of ingroup typicality. In Studies 1 and 2, Black participants (N = 125,915;N = 766) more strongly preferred light-skinned or White relative to dark-skinned or Black individuals the lighter their own skin tone. In Study 3, overweight participants (N = 147,540) more strongly preferred normal-weight relative to overweight individuals the lower their own body weight. In Study 4, participants with disabilities (N = 35,058) more strongly preferred non-disabled relative to disabled individuals the less visible they judged their own disability. Relationships between ingroup typicality and intergroup evaluations were at least partially mediated by ingroup identification (Studies 2 and 3). A meta-analysis across studies yielded an average effect size ofr= .12. Furthermore, higher ingroup typicality was related to both ingroup and outgroup evaluations. We discuss ingroup typicality as an individual constraint to self-group distancing among stigmatized group members and its relation to intergroup evaluations

Dynamical locality of the free scalar field

Dynamical locality is a condition on a locally covariant physical theory, asserting that kinematic and dynamical notions of local physics agree. This condition was introduced in [arXiv:1106.4785], where it was shown to be closely related to the question of what it means for a theory to describe the same physics on different spacetimes. In this paper, we consider in detail the example of the free minimally coupled Klein--Gordon field, both as a classical and quantum theory (using both the Weyl algebra and a smeared field approach). It is shown that the massive theory obeys dynamical locality, both classically and in quantum field theory, in all spacetime dimensions $n\ge 2$ and allowing for spacetimes with finitely many connected components. In contrast, the massless theory is shown to violate dynamical locality in any spacetime dimension, in both classical and quantum theory, owing to a rigid gauge symmetry. Taking this into account (equivalently, working with the massless current) dynamical locality is restored in all dimensions $n\ge 2$ on connected spacetimes, and in all dimensions $n\ge 3$ if disconnected spacetimes are permitted. The results on the quantized theories are obtained using general results giving conditions under which dynamically local classical symplectic theories have dynamically local quantizations.Comment: 34pp, LaTeX2e. Version to appear in Annales Henri Poincar

'Being there' for women with metastatic breast cancer: a pan-European patient survey

BACKGROUND: Understanding their experiences of diagnosis is integral to improving the quality of care for women living with advanced/metastatic breast cancer. METHODS: A survey, initiated in March 2011, was conducted in two stages. First, the views of 47 breast cancer-related patient groups in eight European countries were sought on standards of breast cancer care and unmet needs of patients. Findings were used to develop a patient-centric survey to capture personal experiences of advanced breast cancer to determine insights into the ‘trade-off' between extending overall survival and side effects associated with its treatment. The second online survey was open to women with locally advanced or metastatic breast cancer, or their carers, and responders were recruited through local patient groups. Data were collected via anonymous local language questionnaires. RESULTS: The online stage II survey received a total of 230 responses from 17 European countries: 94% of respondents had locally advanced or metastatic breast cancer and 6% were adult carers. Although the overall experience of care was generally good/excellent (77%), gaps were still perceived in terms of treatment choice and information provision. Treatment choice for patients was felt to be lacking by 32% of responders. In addition, 68% of those who responded would have liked more information about future medical treatments and research, with 57% wishing to receive this information from their oncologist. Two-thirds (66%) of women with advanced breast cancer, or their carers, believed life-extending treatment to be important so that they can spend more time with family and friends, and 67% said that the treatment was worthwhile, despite potential associated side effects. CONCLUSION: These findings show a continuing need to provide women with advanced breast cancer with better information and emphasise the importance that these patients often place on prolonging survival

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Dynamical locality and covariance: What makes a physical theory the same in all spacetimes?

The question of what it means for a theory to describe the same physics on all spacetimes (SPASs) is discussed. As there may be many answers to this question, we isolate a necessary condition, the SPASs property, that should be satisfied by any reasonable notion of SPASs. This requires that if two theories conform to a common notion of SPASs, with one a subtheory of the other, and are isomorphic in some particular spacetime, then they should be isomorphic in all globally hyperbolic spacetimes (of given dimension). The SPASs property is formulated in a functorial setting broad enough to describe general physical theories describing processes in spacetime, subject to very minimal assumptions. By explicit constructions, the full class of locally covariant theories is shown not to satisfy the SPASs property, establishing that there is no notion of SPASs encompassing all such theories. It is also shown that all locally covariant theories obeying the time-slice property possess two local substructures, one kinematical (obtained directly from the functorial structure) and the other dynamical (obtained from a natural form of dynamics, termed relative Cauchy evolution). The covariance properties of relative Cauchy evolution and the kinematic and dynamical substructures are analyzed in detail. Calling local covariant theories dynamically local if their kinematical and dynamical local substructures coincide, it is shown that the class of dynamically local theories fulfills the SPASs property. As an application in quantum field theory, we give a model independent proof of the impossibility of making a covariant choice of preferred state in all spacetimes, for theories obeying dynamical locality together with typical assumptions.Comment: 60 pages, LaTeX. Version to appear in Annales Henri Poincar