Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients

Management of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria. Meta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated. Six studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden. Pre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC

Non-Baryonic Dark Matter - Observational Evidence and Detection Methods

The evidence for the existence of dark matter in the universe is reviewed. A general picture emerges, where both baryonic and non-baryonic dark matter is needed to explain current observations. In particular, a wealth of observational information points to the existence of a non-baryonic component, contributing between around 20 and 40 percent of the critical mass density needed to make the universe geometrically flat on large scales. In addition, an even larger contribution from vacuum energy (or cosmological constant) is indicated by recent observations. To the theoretically favoured particle candidates for non-baryonic dark matter belong axions, supersymmetric particles, and of less importance, massive neutrinos. The theoretical foundation and experimental situation for each of these is reviewed. Direct and indirect methods for detection of supersymmetric dark matter are described in some detail. Present experiments are just reaching the required sensitivity to discover or rule out some of these candidates, and major improvements are planned over the coming years.Comment: Submitted to Reports on Progress in Physics, 59 pages, LaTeX, iopart macro, 14 embedded postscript figure

Spin half fermions with mass dimension one: theory, phenomenology, and dark matter

We provide the first details on the unexpected theoretical discovery of a spin-one-half matter field with mass dimension one. It is based upon a complete set of dual-helicity eigenspinors of the charge conjugation operator. Due to its unusual properties with respect to charge conjugation and parity, it belongs to a non-standard Wigner class. Consequently, the theory exhibits non-locality with (CPT)^2 = - I. We briefly discuss its relevance to the cosmological `horizon problem'. Because the introduced fermionic field is endowed with mass dimension one, it can carry a quartic self-interaction. Its dominant interaction with known forms of matter is via Higgs, and with gravity. This aspect leads us to contemplate the new fermion as a prime dark matter candidate. Taking this suggestion seriously we study a supernova-like explosion of a galactic-mass dark matter cloud to set limits on the mass of the new particle and present a calculation on relic abundance to constrain the relevant cross-section. The analysis favours light mass (roughly 20 MeV) and relevant cross-section of about 2 pb. Similarities and differences with the WIMP and mirror matter proposals for dark matter are enumerated. In a critique of the theory we bare a hint on non-commutative aspects of spacetime, and energy-momentum space.Comment: 78 pages [Changes: referee-suggested improvements, additional important references, and better readability

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

A qualitative exploration of men's experiences of an integrated exercise/CBT mental health promotion programme

This study investigated qualitatively the experiences of men who took part in a 10 week integrated exercise/psychosocial mental health promotion programme, "Back of the Net" (BTN). 15 participants who completed the BTN programme were recruited to participate in either a focus group discussion (N = 9) or individual interview (N = 6). A thematic analytic approach was employed to identify key themes in the data. Results indicated that participants felt that football was a positive means of engaging men in a mental health promotion program. Perceived benefits experienced included perceptions of mastery, social support, positive affect and changes in daily behaviour. The findings support the value of developing gender specific mental health interventions to both access and engage young men. © 2012 by the Men's Studies Press

IKAP/Elp1 Is Required In Vivo for Neurogenesis and Neuronal Survival, but Not for Neural Crest Migration

Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III) manifests from a failure in development of the peripheral sensory and autonomic nervous systems. The disease results from a point mutation in the IKBKAP gene, which encodes the IKAP protein, whose function is still unresolved in the developing nervous system. Since the neurons most severely depleted in the disease derive from the neural crest, and in light of data identifying a role for IKAP in cell motility and migration, it has been suggested that FD results from a disruption in neural crest migration. To determine the function of IKAP during development of the nervous system, we (1) first determined the spatial-temporal pattern of IKAP expression in the developing peripheral nervous system, from the onset of neural crest migration through the period of programmed cell death in the dorsal root ganglia, and (2) using RNAi, reduced expression of IKBKAP mRNA in the neural crest lineage throughout the process of dorsal root ganglia (DRG) development in chick embryos in ovo. Here we demonstrate that IKAP is not expressed by neural crest cells and instead is expressed as neurons differentiate both in the CNS and PNS, thus the devastation of the PNS in FD could not be due to disruptions in neural crest motility or migration. In addition, we show that alterations in the levels of IKAP, through both gain and loss of function studies, perturbs neuronal polarity, neuronal differentiation and survival. Thus IKAP plays pleiotropic roles in both the peripheral and central nervous systems

Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data

Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, we demonstrate that this method is >50% more accurate at identifying functionally related protein pairs than previous approaches. Application to genes involved in yeast chromosome organization identifies a functional map of 91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly, we find that complexes that are enriched for aggravating genetic interactions (i.e., synthetic lethality) are more likely to contain essential genes, linking each of these interactions to an underlying mechanism. These results demonstrate the importance of both large-scale genetic and physical interaction data in mapping pathway architecture and function