Somatic mutation load of estrogen receptor-positive breast tumors predicts overall survival: an analysis of genome sequence data.

Breast cancer is one of the most commonly diagnosed cancers in women. While there are several effective therapies for breast cancer and important single gene prognostic/predictive markers, more than 40,000 women die from this disease every year. The increasing availability of large-scale genomic datasets provides opportunities for identifying factors that influence breast cancer survival in smaller, well-defined subsets. The purpose of this study was to investigate the genomic landscape of various breast cancer subtypes and its potential associations with clinical outcomes. We used statistical analysis of sequence data generated by the Cancer Genome Atlas initiative including somatic mutation load (SML) analysis, Kaplan-Meier survival curves, gene mutational frequency, and mutational enrichment evaluation to study the genomic landscape of breast cancer. We show that ER(+), but not ER(-), tumors with high SML associate with poor overall survival (HR = 2.02). Further, these high mutation load tumors are enriched for coincident mutations in both DNA damage repair and ER signature genes. While it is known that somatic mutations in specific genes affect breast cancer survival, this study is the first to identify that SML may constitute an important global signature for a subset of ER(+) tumors prone to high mortality. Moreover, although somatic mutations in individual DNA damage genes affect clinical outcome, our results indicate that coincident mutations in DNA damage response and signature ER genes may prove more informative for ER(+) breast cancer survival. Next generation sequencing may prove an essential tool for identifying pathways underlying poor outcomes and for tailoring therapeutic strategies

Improvement of rapid cassava processing methods and technology transfer

The aim of this review to summarise research and development activities on cassava processing in East Africa. The approaches taken by relevant projects that are currently underway in Tanzania, Uganda and Mozambique will be considered. These projects are used to highlight the fundamental issues concerning the development of appropriate technology and its successful transfer to end users. The review will be used as part of the development of a work programme for the improvement of cassava processing in Tanzania

Transport and ageing: Extending quality of life for older people via public and private transport

Accessible public transport and the independence that comes with car driving are generally thought to be linked to quality of life in old age. However, there has been almost no research on this topic in the UK. This study by researchers from the University of Paisley and the University of East London used a multi-method approach to explore the relationship between quality of life and access to public and private transport. The study also examined the extent to which the transport needs of older people are taken into account by transport professionals

On-station trials to investigate options to improve the efficiency of cyanogen removal by rapid cassava processing methods

This report provides a preliminary summary of the results of the on-station rapid processing of cassava trials. Further statistical analysis of the results is underway and will contribute towards a further publication on this work

Nystagmus and optical coherence tomography findings in CNGB3-associated achromatopsia

PURPOSE: To describe the nystagmus characteristics of subjects with molecularly confirmed CNGB3-associated achromatopsia and report the spectral domain optical coherence tomography (SD-OCT) findings in these individuals. METHODS: Adults and children with CNGB3-achromatopsia underwent visual acuity testing, ocular motility assessments, video nystagmography, and SD-OCT imaging. Qualitative assessment of foveal structure was performed by grading SD-OCT images into one of five categories. RESULTS: A total of 18 subjects (11 adults) were included. The majority demonstrated a phoria, with manifest strabismus present in only 3 subjects. The predominant nystagmus waveform within the cohort was pure pendular. Nine individuals demonstrated a mixture of waveforms. Nystagmus frequencies were 4-8 cycles/second, with no notable differences in eye movements between adults and children. SD-OCT imaging revealed a continuous ellipsoid zone (EZ) at the fovea in 2 subjects (grade 1) and EZ disruption (grade 2) in the remaining 16. Retinal structure characteristics were symmetrical in both eyes in each subject. CONCLUSIONS: In our study cohort, nystagmus in CNGB3-associated achromatopsia had distinctive features, and the majority of subjects had retinal abnormalities at the fovea on SD-OCT. Early use of SD-OCT in the clinical work-up may eliminate the need for more invasive investigations, such as neuro-imaging

The effectiveness of implementation in Indigenous Australian healthcare: An overview of literature reviews

© 2016 McCalman et al. Background: Effective implementation can maximise the beneficial impacts of health services. It is therefore important to review implementation in the context of Indigenous populations, who suffer some of the greatest disadvantage within developed countries. This paper analyses Aboriginal and Torres Strait Islander (hereafter Indigenous) Australian health implementation reviews to examine the research question: What is the effectiveness of implementation, as reported in the Indigenous Australian health implementation literature? Methods: Eight databases were systematically searched to find reviews of Indigenous Australian health services and/or programs where implementation was the focus. Search terms included Aborigin∗OR Indigen∗OR Torres AND health AND service OR program∗OR intervention AND implementation (or like terms) AND Australia AND review. Review findings were analysed through the lens of the PARiHS framework which theorises that successful implementation occurs through the interplay of evidence, context and facilitation. The review followed Cochrane methods but was not registered. Results: Six reviews were found; these encompassed 107 studies that considered health service/program implementation. Included studies described many health services implemented across Australia as not underpinned by rigorous impact evaluation; nevertheless implementers tended to prefer evidence-based interventions. Effective implementation was supported by clearly defined management systems, employment of Indigenous health workers as leaders, community control, partnerships, tailoring for diverse places and settings; and active facilitation methods. Short-term funding meant most studies focused on implementation in one site through pilot initiatives. Only two mentioned cost effectiveness. Indigenous Australian studies incorporated two elements not included in the PARiHS reference guide: the value of community control and equity of service provision across sites. Conclusions: Comparison of the Indigenous Australian review findings against the PARiHS reference guide elements suggested a fledgling but growing state of Indigenous implementation research, and considerable scope to improve the effectiveness of implementation. Further research is required to explore Indigenous people's understandings of what is important in healthcare implementation; particularly in relation to the value of community control and equity issues

Longitudinal measurement of the developing grey matter in preterm subjects using multi-modal MRI.

Preterm birth is a major public health concern, with the severity and occurrence of adverse outcome increasing with earlier delivery. Being born preterm disrupts a time of rapid brain development: in addition to volumetric growth, the cortex folds, myelination is occurring and there are changes on the cellular level. These neurological events have been imaged non-invasively using diffusion-weighted (DW) MRI. In this population, there has been a focus on examining diffusion in the white matter, but the grey matter is also critically important for neurological health. We acquired multi-shell high-resolution diffusion data on 12 infants born at ≤28weeks of gestational age at two time-points: once when stable after birth, and again at term-equivalent age. We used the Neurite Orientation Dispersion and Density Imaging model (NODDI) (Zhang et al., 2012) to analyse the changes in the cerebral cortex and the thalamus, both grey matter regions. We showed region-dependent changes in NODDI parameters over the preterm period, highlighting underlying changes specific to the microstructure. This work is the first time that NODDI parameters have been evaluated in both the cortical and the thalamic grey matter as a function of age in preterm infants, offering a unique insight into neuro-development in this at-risk population

A far-UV survey of three hot, metal-polluted white dwarf stars: WD0455-282, WD0621-376, and WD2211-495

Using newly obtained high-resolution data ($R\sim{1\times{10}^{5}}$) from the \textit{Hubble Space Telescope}, and archival UV data from the \textit{Far Ultraviolet Spectroscopic Explorer} we have conducted a detailed UV survey of the three hot, metal-polluted white dwarfs WD0455-282, WD0621-376, and WD2211-495. Using bespoke model atmospheres we measured $T_{\mathrm{eff}}$, log $g$, and photospheric abundances for these stars. In conjunction with data from Gaia we measured masses, radii, and gravitational redshift velocities for our sample of objects. We compared the measured photospheric abundances with those predicted by radiative levitation theory, and found that the observed Si abundances in all three white dwarfs, and the observed Fe abundances in WD0621-376 and WD2211-495, were larger than those predicted by an order of magnitude. These findings imply not only an external origin for the metals, but also ongoing accretion, as the metals not supported by radiative levitation would sink on extremely short timescales. We measured the radial velocities of several absorption features along the line of sight to the three objects in our sample, allowing us to determine the velocities of the photospheric and interstellar components along the line of sight for each star. Interestingly, we made detections of circumstellar absorption along the line of sight to WD0455-282 with three velocity components. To our knowledge, this is the first such detection of multi-component circumstellar absorption along the line of sight to a white dwarf.Comment: 19 pages, 23 figures, 8 tables. Accepted for publication in the Monthly Notices of the Royal Astronomical Societ

Severe Loss of Tritan Color Discrimination in RPE65 Associated Leber Congenital Amaurosis

Purpose: RPE65-associated Leber congenital amaurosis (RPE65-LCA) is a progressive severe retinal dystrophy with early profound dysfunction of rod photoreceptors followed by progressive cone photoreceptor degeneration. We aim to provide detailed information about how cone dysfunction affects color discrimination. Methods: Seven adults (aged 16-21) with RPE65-LCA underwent monocular color discrimination assessment using the Trivector and Ellipse versions of three computerized tests: Cambridge Colour Test (CCT), low vision version of the Cambridge Colour Test (lvvCCT), and the Universal Colour Discrimination Test (UCDT). For comparison, subjects were also tested using the American Optical Hardy Rand Rittler (AO-HRR) plates. Each assessment was repeated three times. Results: The Trivector version of the tests demonstrated that color discrimination along the tritan axis was undetectable in four subjects, and severely reduced in three subjects. These findings were confirmed by the Ellipse version of the tests. Color discrimination along the protan and deutan axes was evident but reduced in six of seven subjects. Four of seven subjects were unable to read any of the HRR plates. Conclusions: The computerized color vision tests adopted in this study provide detailed information about color discrimination in adult RPE65-LCA patients. The condition is associated with severe impairment of color discrimination, particularly along the tritan axis indicating possible early involvement of S-cones, with additional protan and deutan loss to a lesser extent. This psychophysical assessment strategy is likely to be valuable in measuring the impact of therapeutic intervention on cone function