Joint and individual variation explained (JIVE) for integrated analysis of multiple data types

Research in several fields now requires the analysis of data sets in which multiple high-dimensional types of data are available for a common set of objects. In particular, The Cancer Genome Atlas (TCGA) includes data from several diverse genomic technologies on the same cancerous tumor samples. In this paper we introduce Joint and Individual Variation Explained (JIVE), a general decomposition of variation for the integrated analysis of such data sets. The decomposition consists of three terms: a low-rank approximation capturing joint variation across data types, low-rank approximations for structured variation individual to each data type, and residual noise. JIVE quantifies the amount of joint variation between data types, reduces the dimensionality of the data and provides new directions for the visual exploration of joint and individual structures. The proposed method represents an extension of Principal Component Analysis and has clear advantages over popular two-block methods such as Canonical Correlation Analysis and Partial Least Squares. A JIVE analysis of gene expression and miRNA data on Glioblastoma Multiforme tumor samples reveals gene-miRNA associations and provides better characterization of tumor types. Data and software are available at https://genome.unc.edu/jive/Comment: Published in at http://dx.doi.org/10.1214/12-AOAS597 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

WS01.05 Development of a musculoskeletal screening tool for children and young people with cystic fibrosis (Addenbrooke’s MST): initial findings

© 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/Objectives: Development of the Addenbrooke’s Musculoskeletal Screening Tool (MST) for children and young people (CYP) with CF. It is recommended by the Association of Chartered Physiotherapists in CF that Musculoskeletal (MSK) screening is carried out in all children from 7 years of age. Currently there is no specific tool for CYP with CF, only the Adult Manchester MST is available in CF (Ashbrook, Taylor and Jones, 2011). Methods: A paediatric MST was constructed by reviewing the Manchester MSK Screening Tool, the pGALS and recent literature surrounding both paediatric and CF related MSK conditions. The tool was developed with support from paediatric CF specialist physiotherapists, paediatric MSK specialist physiotherapists and respiratory consultants. This tool was then used over a one year period on a total of 58 CYP. Results: The MST was well accepted by clinicians and CYP, taking up to 5 minutes to complete. There were 81.8% more positive MSK screens in the year using this Addenbrooke’s MST (20) compared to the previous year using the Manchester MST (11). There were also 6 more referrals, all deemed appropriate by MSK specialist physiotherapists. MSK advice was given to 83% more children in the year using AMST (11) compared to the year using MMST (6). Urinary incontinence appears to be under reported in this population when comparing to other studies with only two positive screens. Kyphosis (as diagnosed by plumb line) was particularly prevalent in this population (20%) and those with kyphosis had a significantly reduced FEV1% (p = 0.008) and FVC% (p = 0.034), as well as tighter pectoralis major (p = 0.002). Conclusion: A screening tool designed for CYP with CF is important in identifying specific conditions to this population. There is an increased number of appropriate referrals when using this tool and interesting initial evidence on the use of pectoralis major length as an outcome measure, however further research and validation is required.Peer reviewe

A case study of boundary layer ventilation by convection and coastal processes

It is often assumed that ventilation of the atmospheric boundary layer is weak in the absence of fronts, but is this always true? In this paper we investigate the processes responsible for ventilation of the atmospheric boundary layer during a nonfrontal day that occurred on 9 May 2005 using the UK Met Office Unified Model. Pollution sources are represented by the constant emission of a passive tracer everywhere over land. The ventilation processes observed include shallow convection, turbulent mixing followed by large-scale ascent, a sea breeze circulation and coastal outflow. Vertical distributions of tracer are validated qualitatively with AMPEP (Aircraft Measurement of chemical Processing Export fluxes of Pollutants over the UK) CO aircraft measurements and are shown to agree impressively well. Budget calculations of tracers are performed in order to determine the relative importance of these ventilation processes. Coastal outflow and the sea breeze circulation were found to ventilate 26% of the boundary layer tracer by sunset of which 2% was above 2 km. A combination of coastal outflow, the sea breeze circulation, turbulent mixing and large-scale ascent ventilated 46% of the boundary layer tracer, of which 10% was above 2 km. Finally, coastal outflow, the sea breeze circulation, turbulent mixing, large-scale ascent and shallow convection together ventilated 52% of the tracer into the free troposphere, of which 26% was above 2 km. Hence this study shows that significant ventilation of the boundary layer can occur in the absence of fronts (and thus during high-pressure events). Turbulent mixing and convection processes can double the amount of pollution ventilated from the boundary layer

Exploratory Analysis of Exercise Adherence Patterns With Sedentary Pregnant Women

It is not well understood how sedentary women who wish to engage in regular exercise adhere to interventions during pregnancy and what factors may influence adherence over time

On isovector meson exchange currents in the Bethe-Salpeter approach

We investigate the nonrelativistic reduction of the Bethe-Salpeter amplitude for the deuteron electrodisintegration near threshold energies. To this end, two assumptions have been used in the calculations: 1) the static approximation and 2) the one iteration approximation. Within these assumptions it is possible to recover the nonrelativistic result including a systematic extension to relativistic corrections. We find that the so-called pair current term can be constructed from the $P$-wave contribution of the deuteron Bethe-Salpeter amplitude. The form factor that enters into the calculation of the pair current is constrained by the manifestly gauge independent matrix elements.Comment: 15 pages, incl. 3 figures, to be published Phys. Rev.

BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma

The expression of the BCL-2 family proteins, BCL-2, BAX, BCLXLand BAK have been determined in a panel of 12 human ovarian carcinoma cell lines encompassing a wide range in sensitivity to cisplatin. Whereas BAX, BCLXLand BAK levels did not correlate with sensitivity, there was a statistically significant inverse correlation (r = –0.81;P = 0.002) between growth inhibition by cisplatin and BCL-2 levels. In sublines possessing acquired resistance to various platinum-based drugs or across a panel of human ovarian carcinoma xenografts, there was no consistent pattern of BCL-2 expression. Two relatively sensitive lines (A2780 and CH1) have been stably transfected with bcl-2 and bclXLrespectively and two relatively resistant lines (A2780cisR and SKOV-3) stably transfected with bax. Overexpression of BCL-2 in A2780 cells led to resistance to cisplatin compared to the vector control when assayed at 48 h post-drug incubation but a significant increase in sensitivity at 96 h. Relative rates of apoptosis at 48- and 96-h post-cisplatin exposure mirrored the growth inhibition. There was no significant difference in sensitivity of the pair of lines by clonogenic assay. No significant changes in chemosensitivity to a variety of DNA-damaging or tubulin-interactive agents were observed in the remaining transfected lines. Taken together, these results suggest that, in human ovarian carcinoma cells, high BCL-2 levels (either naturally occurring or through gene transfection) confers a trend towards sensitivity not resistance to platinum drugs. © 2000 Cancer Research Campaig

A Fermi Surface study of Ba1−x_{1-x}Kx_{x}BiO3_{3}

We present all electron computations of the 3D Fermi surfaces (FS's) in Ba$_{1-x}$K$_{x}$BiO$_{3}$ for a number of different compositions based on the selfconsistent Korringa-Kohn-Rostoker coherent-potential-approximation (KKR-CPA) approach for incorporating the effects of Ba/K substitution. By assuming a simple cubic structure throughout the composition range, the evolution of the nesting and other features of the FS of the underlying pristine phase is correlated with the onset of various structural transitions with K doping. A parameterized scheme for obtaining an accurate 3D map of the FS in Ba$_{1-x}$K$_{x}$BiO$_{3}$ for an arbitrary doping level is developed. We remark on the puzzling differences between the phase diagrams of Ba$_{1-x}$K$_{x}$BiO$_{3}$ and BaPb$_{x}$Bi$_{1-x}$O$_{3}$ by comparing aspects of their electronic structures and those of the end compounds BaBiO$_{3}$, KBiO$_3$ and BaPbO$_3$. Our theoretically predicted FS's in the cubic phase are relevant for analyzing high-resolution Compton scattering and positron-annihilation experiments sensitive to the electron momentum density, and are thus amenable to substantial experimental verification.Comment: 12 pages, 7 figures, to appear in Phys. Rev.

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015