275 research outputs found
Regulator constants and the parity conjecture
The p-parity conjecture for twists of elliptic curves relates multiplicities
of Artin representations in p-infinity Selmer groups to root numbers. In this
paper we prove this conjecture for a class of such twists. For example, if E/Q
is semistable at 2 and 3, K/Q is abelian and K^\infty is its maximal pro-p
extension, then the p-parity conjecture holds for twists of E by all orthogonal
Artin representations of Gal(K^\infty/Q). We also give analogous results when
K/Q is non-abelian, the base field is not Q and E is replaced by an abelian
variety. The heart of the paper is a study of relations between permutation
representations of finite groups, their "regulator constants", and
compatibility between local root numbers and local Tamagawa numbers of abelian
varieties in such relations.Comment: 50 pages; minor corrections; final version, to appear in Invent. Mat
Pupil responses associated with coloured afterimages are mediated by the magno-cellular pathway
Sustained fixation of a bright coloured stimulus will, on extinction of the stimulus and continued steady fixation, induce an afterimage whose colour is complementary to that of the initial stimulus; an effect thought to be caused by fatigue of cones and/or of cone-opponent processes to different colours. However, to date, very little is known about the specific pathway that causes the coloured afterimage. Using isoluminant coloured stimuli recent studies have shown that pupil constriction is induced by onset and offset of the stimulus, the latter being attributed specifically to the subsequent emergence of the coloured afterimage. The aim of the study was to investigate how the offset pupillary constriction is generated in terms of input signals from discrete functional elements of the magno- and/or parvo-cellular pathways, which are known principally to convey, respectively, luminance and colour signals. Changes in pupil size were monitored continuously by digital analysis of an infra-red image of the pupil while observers viewed isoluminant green pulsed, ramped or luminance masked stimuli presented on a computer monitor. It was found that the amplitude of the offset pupillary constriction decreases when a pulsed stimulus is replaced by a temporally ramped stimulus and is eliminated by a luminance mask. These findings indicate for the first time that pupillary constriction associated with a coloured afterimage is mediated by the magno-cellular pathway. © 2003 Elsevier Science Ltd. All rights reserved
Simulation techniques for cosmological simulations
Modern cosmological observations allow us to study in great detail the
evolution and history of the large scale structure hierarchy. The fundamental
problem of accurate constraints on the cosmological parameters, within a given
cosmological model, requires precise modelling of the observed structure. In
this paper we briefly review the current most effective techniques of large
scale structure simulations, emphasising both their advantages and
shortcomings. Starting with basics of the direct N-body simulations appropriate
to modelling cold dark matter evolution, we then discuss the direct-sum
technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and
the tree algorithms. Simulations of baryonic matter in the Universe often use
hydrodynamic codes based on both particle methods that discretise mass, and
grid-based methods. We briefly describe Eulerian grid methods, and also some
variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science
Reviews, special issue "Clusters of galaxies: beyond the thermal view",
Editor J.S. Kaastra, Chapter 12; work done by an international team at the
International Space Science Institute (ISSI), Bern, organised by J.S.
Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
Ranks of twists of elliptic curves and Hilbert's Tenth Problem
In this paper we investigate the 2-Selmer rank in families of quadratic
twists of elliptic curves over arbitrary number fields. We give sufficient
conditions on an elliptic curve so that it has twists of arbitrary 2-Selmer
rank, and we give lower bounds for the number of twists (with bounded
conductor) that have a given 2-Selmer rank. As a consequence, under appropriate
hypotheses we can find many twists with trivial Mordell-Weil group, and
(assuming the Shafarevich-Tate conjecture) many others with infinite cyclic
Mordell-Weil group. Using work of Poonen and Shlapentokh, it follows from our
results that if the Shafarevich-Tate conjecture holds, then Hilbert's Tenth
Problem has a negative answer over the ring of integers of every number field.Comment: Minor changes. To appear in Inventiones mathematica
Infancy, autism, and the emergence of a socially disordered body
Twenty academic psychologists and neuroscientists, with an interest in autism and based within the
United Kingdom, were interviewed between 2012 and 2013 on a variety of topics related to the condition.
Within these qualitative interviews researchers often argued that there had been a ‘turn to infancy’
since the beginning of the 21st century with focus moving away from the high functioning adolescent
and towards the pre-diagnostic infant deemed to be ‘at risk’ of autism. The archetypal research of this
type is the ‘infant sibs’ study whereby infants with an elder sibling already diagnosed with autism are
subjected to a range of tests, the results of which are examined only once it becomes apparent whether
that infant has autism. It is claimed in this paper that the turn to infancy has been facilitated by two
phenomena; the autism epidemic of the 1990s and the emergence of various methodological techniques,
largely although not exclusively based within neuroscience, which seek to examine social disorder in the
absence of comprehension or engagement on the part of the participant: these are experiments done to
participants rather than with them. Interviewees claimed that these novel methods allowed researchers
to see a ‘real’ autism that lay ‘behind’ methodology. That claim is disputed here and instead it is argued
that these emerging methodologies other various phenomena, reorienting the social abnormality
believed typical of autism away from language and meaning and towards the body. The paper concludes
by suggesting that an attempt to draw comparisons between the symptoms of autism in infant populations
and adults with the condition inevitably leads to a somaticisation of autism
SARS-CoV-2 wastewater surveillance for public health action
Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has garnered extensive public attention during the coronavirus disease pandemic as a proposed complement to existing disease surveillance systems. Over the past year, methods for detection and quantifi cation of SARS-CoV-2 viral RNA in untreated sewage have advanced, and concentrations in wastewater have been shown to correlate with trends in reported cases. Despite the promise of wastewater surveillance, for these measurements to translate into useful public health tools, bridging the communication and knowledge gaps between researchers and public health responders is needed. We describe the key uses, barriers, and applicability of SARS-CoV-2 wastewater surveillance for supporting public health decisions and actions, including establishing ethics consideration for monitoring. Although wastewater surveillance to assess community infections is not a new idea, the coronavirus disease pandemic might be the initiating event to make this emerging public health tool a sustainable nationwide surveillance system, provided that these barriers are addressed
The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice
More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease
Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)
BACKGROUND:
Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.
METHODS:
Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights.
FINDINGS:
5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease.
INTERPRETATION:
International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes
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