Aquatics reconstruction software: the design of a diagnostic tool based on computer vision algorithms

Computer vision methods can be applied to a variety of medical and surgical applications, and many techniques and algorithms are available that can be used to recover 3D shapes and information from images range and volume data. Complex practical applications, however, are rarely approachable with a single technique, and require detailed analysis on how they can be subdivided in subtasks that are computationally treatable and that, at the same time, allow for the appropriate level of user-interaction. In this paper we show an example of a complex application where, following criteria of efficiency, reliability and user friendliness, several computer vision techniques have been selected and customized to build a system able to support diagnosis and endovascular treatment of Abdominal Aortic Aneurysms. The system reconstructs the geometrical representation of four different structures related to the aorta (vessel lumen, thrombus, calcifications and skeleton) from CT angiography data. In this way it supports the three dimensional measurements required for a careful geometrical evaluation of the vessel, that is fundamental to decide if the treatment is necessary and to perform, in this case, its planning. The system has been realized within the European trial AQUATICS (IST-1999-20226 EUTIST-M WP 12), and it has been widely tested on clinical data

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Characterising the Atmospheres of Transiting Planets with a Dedicated Space Telescope

Exoplanetary science is one of the fastest evolving fields of today's astronomical research, continuously yielding unexpected and surprising results. Ground-based planet-hunting surveys, together with dedicated space missions such as Kepler and CoRoT, are delivering an ever-increasing number of exoplanets, over 690, and ESA's Gaia mission will escalate the exoplanetary census into the several thousands. The next logical step is the characterization of these new worlds. What is their nature? Why are they as they are? Use of the Hubble Space Telescope and Spitzer Space Telescope to probe the atmospheres of transiting hot, gaseous exoplanets has opened perspectives unimaginable even just 10 years ago, demonstrating that it is indeed possible with current technology to address the ambitious goal of characterizing the atmospheres of these alien worlds. However, these successful measurements have also shown the difficulty of understanding the physics and chemistry of these exotic environments when having to rely on a limited number of observations performed on a handful of objects. To progress substantially in this field, a dedicated facility for exoplanet characterization, able to observe a statistically significant number of planets over time and a broad spectral range will be essential. Additionally, the instrument design (e.g., detector performances, photometric stability) will be tailored to optimize the extraction of the astrophysical signal. In this paper, we analyze the performance and tradeoffs of a 1.2/1.4 m space telescope for exoplanet transit spectroscopy from the visible to the mid-IR. We present the signal-to-noise ratio as a function of integration time and stellar magnitude/spectral type for the acquisition of spectra of planetary atmospheres for a variety of scenarios: hot, warm, and temperate planets orbiting stars ranging in spectral type from hot F- to cooler M-dwarfs. Our results include key examples of known planets (e.g., HD 189733b, GJ 436b, GJ 1214b, and Cancri 55 e) and simulations of plausible terrestrial and gaseous planets, with a variety of thermodynamical conditions. We conclude that even most challenging targets, such as super-Earths in the habitable zone of late-type stars, are within reach of an M-class, space-based spectroscopy mission

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

Determinants of cognitive function in childhood: A cohort study in a middle income context

BACKGROUND: There is evidence that poverty, health and nutrition affect children's cognitive development. This study aimed to examine the relative contributions of both proximal and distal risk factors on child cognitive development, by breaking down the possible causal pathways through which poverty affects cognition. METHODS: This cohort study collected data on family socioeconomic status, household and neighbourhood environmental conditions, child health and nutritional status, psychosocial stimulation and nursery school attendance. The effect of these on Wechsler Pre-School and Primary Scale of Intelligence scores at five years of age was investigated using a multivariable hierarchical analysis, guided by the proposed conceptual framework. RESULTS: Unfavourable socioeconomic conditions, poorly educated mother, absent father, poor sanitary conditions at home and in the neighbourhood and low birth weight were negatively associated with cognitive performance at five years of age, while strong positive associations were found with high levels of domestic stimulation and nursery school attendance. CONCLUSION: Children's cognitive development in urban contexts in developing countries could be substantially increased by interventions promoting early psychosocial stimulation and preschool experience, together with efforts to prevent low birth weight and promote adequate nutritional status