Brain age predicts mortality

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death

Surprisingly Simple Spectra

The large N limit of the anomalous dimensions of operators in ${\cal N}=4$ super Yang-Mills theory described by restricted Schur polynomials, are studied. We focus on operators labeled by Young diagrams that have two columns (both long) so that the classical dimension of these operators is O(N). At large N these two column operators mix with each other but are decoupled from operators with $n\ne 2$ columns. The planar approximation does not capture the large N dynamics. For operators built with 2, 3 or 4 impurities the dilatation operator is explicitly evaluated. In all three cases, in a certain limit, the dilatation operator is a lattice version of a second derivative, with the lattice emerging from the Young diagram itself. The one loop dilatation operator is diagonalized numerically. All eigenvalues are an integer multiple of $8g_{YM}^2$ and there are interesting degeneracies in the spectrum. The spectrum we obtain for the one loop anomalous dimension operator is reproduced by a collection of harmonic oscillators. This equivalence to harmonic oscillators generalizes giant graviton results known for the BPS sector and further implies that the Hamiltonian defined by the one loop large $N$ dilatation operator is integrable. This is an example of an integrable dilatation operator, obtained by summing both planar and non-planar diagrams.Comment: 34 page

The entropy of black holes: a primer

After recalling the definition of black holes, and reviewing their energetics and their classical thermodynamics, one expounds the conjecture of Bekenstein, attributing an entropy to black holes, and the calculation by Hawking of the semi-classical radiation spectrum of a black hole, involving a thermal (Planckian) factor. One then discusses the attempts to interpret the black-hole entropy as the logarithm of the number of quantum micro-states of a macroscopic black hole, with particular emphasis on results obtained within string theory. After mentioning the (technically cleaner, but conceptually more intricate) case of supersymmetric (BPS) black holes and the corresponding counting of the degeneracy of Dirichlet-brane systems, one discusses in some detail the ``correspondence'' between massive string states and non-supersymmetric Schwarzschild black holes.Comment: 51 pages, 4 figures, talk given at the "Poincare seminar" (Paris, 6 December 2003), to appear in Poincare Seminar 2003 (Birkhauser

Thresholds of large N factorization in CFT4: exploring bulk spacetime in AdS(5)

52 pages, 6 figures52 pages, 6 figure

Tensor and Matrix models: a one-night stand or a lifetime romance?

The spectra of energy eigenstates of free tensor and matrix models are organized by Kronecker coefficients and Littlewood-Richardson numbers, respectively. Exploiting recent results in combinatorics for Kronecker coefficients, we derive a formula that relates Kronecker coefficients with a hook shape with Littlewood-Richardson numbers. This formula has a natural translation into physics: the eigenstates of the hook sector of tensor models are in one-to-one correspondence with fluctuations of 1/2-BPS states in multi-matrix models. We then conjecture the duality between both sectors. Finally, we study the Hagedorn behaviour of tensor models with finite rank of the symmetry group and, using similar arguments, suggest that the second (high energy) phase could be entirely described by multi-matrix models.Comment: 20 pages, 1 figure. References adde

The giant graviton on AdS_{4} x CP^{3} - another step towards the emergence of geometry

We construct the giant graviton on AdS_{4} x CP^{3} out of a four-brane embedded in and moving on the complex projective space. This configuration is dual to the totally anti-symmetric Schur polynomial operator \chi_{R}(A_{1}B_{1}) in the 2+1-dimensional, N = 6 super Chern-Simons ABJM theory. We demonstrate that this BPS solution of the D4-brane action is energetically degenerate with the point graviton solution and initiate a study of its spectrum of small fluctuations. Although the full computation of this spectrum proves to be analytically intractable, by perturbing around a "small'" giant graviton, we find good evidence for a dependence of the spectrum on the size, \alpha_{0}, of the giant. This is a direct result of the changing shape of the worldvolume as it grows in size.Comment: 46 pages, 7 figures. Further details added to section 6 - the solutions to the leading order fluctuation equations and the leading order spectrum have been obtained - and additional comments added to the discussion. Additional references added. Mistake in section 2 correcte

Product Diversity and Spectrum of Choice in Hospital ePrescribing Systems in England

Background: ePrescribing systems have considerable potential for improving healthcare quality and safety. With growing expectations about the benefits of such systems, there is evidence of widespread plans to implement these systems in hospitals in England where hitherto they have had a low uptake. Given the international drive away from developing home-grown to systems to procuring commercial applications, we aimed to identify available ePrescribing systems in England and to use the findings to develop a taxonomy of the systems offered by suppliers. Methods and Findings: We undertook a scoping review of the published and grey literature, and conducted expert interviews with vendors, healthcare organisations and national ePrescribing experts in order to identify the spectrum of available systems, identify and map their key features, and then iteratively develop and validate a taxonomy of commercial ePrescribing systems available to English hospitals. There is a wide range of available systems including 13 hospital-wide applications and a range of specialty systems. These commercial applications can be grouped into four sub-categories: standalone systems, modules within integrated systems, functionalities spread over several modules, and specialty systems. The findings also reveal that apart from four packaged applications (two of which are specialty systems), all other systems have none or less than two live implementations across England. Conclusions: The wide range of products developed in the last few years by different national and international suppliers, and the low uptake of these products by English hospitals indicate that the English ePrescribing market is still in its infancy. This market is undergoing rapid cycles of change, both with respect to the number of suppliers and their diversity of offerings. Constant renewal of knowledge is needed on the status of this evolving market, encompassing the products development and adoption, to assist implementation decisions and facilitate market maturity

Lessons from giant gravitons on AdS5×T1,1AdS_{5}\times T^{1,1}

We implement Mikhailov's holomorphic curve construction to explore various properties of giant gravitons in type IIB string theory on $AdS_{5}\times T^{1,1}$. By coloring the D-brane worldvolume, we are able to show how, in the string theory, the giant graviton factorizes at its maximal size into two dibaryons - topologically stable D-branes wrapping non-contractible cycles in the $T^{1,1}$. This is related to the structure of the symmetry group of the emergent Klebanov-Witten gauge theory being a product - $SU(N) \times SU(N)$ instead of the canonical $SU(N)$. Finally, we complete this study with a systematic and detailed construction of the spectrum of small fluctuations about the giant graviton configuration. Curiously, we find that the fluctuation spectrum depends on the size of the giant. The similarity of the operator structures in the Klebanov-Witten and ABJM theories leads us to believe that the D4-brane giant graviton in type IIA string theory on $AdS_{4}\times \mathbb{CP}^{3}$ factorizes into two $\mathbb{CP}^{2}$ dibaryons in a qualitatively similar way.Comment: 39 pages; abstract reworded slightly; additional comments included in subsection 3.3; section 5 revised with the addition of subsection 5.3; added reference

Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis.

Cancer genome sequencing studies have identified numerous driver genes, but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from premalignant Barrett's esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently mutated genes and assessed clonal structure using whole-genome sequencing and amplicon resequencing of 112 EACs. We next screened a cohort of 109 biopsies from 2 key transition points in the development of malignancy: benign metaplastic never-dysplastic Barrett's esophagus (NDBE; n=66) and high-grade dysplasia (HGD; n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 mutations occurred in a stage-specific manner, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett's esophagus in a new non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies

A distinct role for B1b lymphocytes in T cell-independent immunity

Pathogenesis of infectious disease is not only determined by the virulence of the microbe but also by the immune status of the host. Vaccination is the most effective means to control infectious diseases. A hallmark of the adaptive immune system is the generation of B cell memory, which provides a long-lasting protective antibody response that is central to the concept of vaccination. Recent studies revealed a distinct function for B1b lymphocytes, a minor subset of mature B cells that closely resembles that of memory B cells in a number of aspects. In contrast to the development of conventional B cell memory, which requires the formation of germinal centers and T cells, the development of B1b cell-mediated long-lasting antibody responses occurs independent of T cell help. T cell-independent (TI) antigens are important virulence factors expressed by a number of bacterial pathogens, including those associated with biological threats. TI antigens cannot be processed and presented to T cells and therefore are known to possess restricted T cell-dependent (TD) immunogenicity. Nevertheless, specific recognition of TI antigens by B1b cells and the highly protective antibody responses mounted by them clearly indicate a crucial role for this subset of B cells. Understanding the mechanisms of long-term immunity conferred by B1b cells may lead to improved vaccine efficacy for a variety of TI antigens