Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

FIC/FEM formulation with matrix stabilizing terms for incompressible flows at low and high Reynolds numbers

The final publication is available at Springer via http://dx.doi.org/10.1007/s00466-006-0060-yWe present a general formulation for incompressible fluid flow analysis using the finite element method. The necessary stabilization for dealing with convective effects and the incompressibility condition are introduced via the Finite Calculus method using a matrix form of the stabilization parameters. This allows to model a wide range of fluid flow problems for low and high Reynolds numbers flows without introducing a turbulence model. Examples of application to the analysis of incompressible flows with moderate and large Reynolds numbers are presented.Peer ReviewedPostprint (author's final draft

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

Testing the isotropy of the dark energy Survey's extreme trans-neptunian objects

We test whether the population of "extreme"trans-Neptunian objects (eTNOs) detected in the first four years of the Dark Energy Survey (DES Y4) data exhibit azimuthal asymmetries that might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population that, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements a, e, and i as well as absolute magnitude H, but has uniform distributions in mean anomaly M, longitude of ascending node Ω, and argument of perihelion ω. We then compare the detected distributions in each of Ω, ω, and the longitude of perihelion {equation presented} to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of four definitions of the eTNO population, choosing among a > (150, 250) au and perihelion q > (30, 37) au. These choices yield 3-7 eTNOs in the DES Y4 sample. Among the 12 total tests, two have the likelihood of drawing the observed angles from the isotropic population at p 250 and q > 37 au and the four detections at a > 250 and q > 30 au have a Ω distribution with p ≈ 0.03 coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9"hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis

Testing the isotropy of the Dark Energy Survey's extreme trans-Neptunian objects

We test whether the population of "extreme" trans-Neptunian objects (eTNOs) detected in the Y4 Dark Energy Survey (DES) data exhibit azimuthal asymmetries which might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population which, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements $a,e,$ and $i$ as well as absolute magnitude $H$, but has uniform distributions in mean anomaly $M$, longitude of ascending node $\Omega,$ and argument of perihelion $\omega.$ We then compare the detected distributions in each of $\Omega, \omega,$ and $\varpi\equiv\Omega+\omega$ to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of 4 definitions of the eTNO population, choosing among $a>(150,250)$ AU and perihelion $q>(30,37)$ AU. These choices yield 3--7 eTNOs in the DES Y4 sample. Among the twelve total tests, two have the likelihood of drawing the observed angles from the isotropic population at $p250, q>37$ AU, and the 4 detections at $a>250, q>30$ AU, have $\Omega$ distribution with $p=0.03$ of coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9" hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis.Comment: Accepted on PS

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Exploring the potential of civic engagement to strengthen mental health systems in Indonesia (IGNITE) : a study protocol

Background Indonesia has the highest rate of years of life lost to disability or early death from Schizophrenia than any other country in the world. More than 90% of people with mental illness do not get any treatment and tens of thousands of people with psychosis are illegally detained ('pasung') in the family home. Civic engagement, a core part of the recent World Health Organisation global strategy, has the potential to address some of these challenges through the development of person-centered models of care. The aim of the study is to develop a testable systems level, culturally appropriate, civic engagement framework for use in Jakarta and Bogor, Indonesia to strengthen local mental health services. Methods A mixed methods study underpinned by a realist approach will be undertaken across four phases in two study sites in Indonesia (Jakarta and Bogor). Phase 1 will explore the use of civic engagement across South East Asia by conducting a systematic review of existing evidence. By surveying 300 mental health professionals, phase 2 will identify the stakeholders, the sources of collaboration and the evidence used by professionals in decision making within local mental health systems and identify potential opportunities for civic engagement within the system. In order to explore the potential use of civic engagement within Indonesian mental health services and identify priorities for a culturally appropriate framework, phase 3 will undertake two focus groups with participants with experience of psychosis or caring for someone with psychosis (n = 20–30). Professionals and other key decision makers in a range of roles across the system at a national (n = 5) and local level (n = 10–15/site) will also take part in semi-structured interviews. Phase 4 will co-produce a civic engagement framework for use in Indonesia by synthesising evidence from phases 1–3 collaboratively with key stakeholders. Discussion Civic engagement is a potential way in which health services in low and middle income countries can address the burden of mental health conditions through the development of person-centred models of care. However, such approaches are underexplored in Indonesia. This study will work with local stakeholders to design a testable civic engagement framework for use in mental health services in Indonesia