The Coxian phase-type distribution as a contribution to the multilevel model of in-hospital mortality

This paper presents multilevel models that utilize the Coxian phase-type distribution in order to be able to include a survival component in the model. The approach is demonstrated by modeling patient length of stay and in-hospital mortality in geriatric wards in Italy. The multilevel model is used to provide a means of controlling for the existence of possible intra-ward correlations, which may make patients within a hospital more alike in terms of experienced outcome than patients coming from different hospitals, everything else being equal. Within this multilevel model we introduce the use of the Coxian phase-type distribution to create a covariate that represents patient length of stay or stage (of hospital care). Results demonstrate that the use of the multilevel model for representing the in-patient mortality is successful and further enhanced by the inclusion of the Coxian phase-type distribution variable (stage covariate).

Trends and Determinants of Work-Retirement Transitions under Changing Institutional Conditions: Germany, England and Japan compared

Many governments world-wide are promoting longer working life due to the social and economic repercussions of demographic change. However, not all workers are equally able to extend their employment careers. Thus, while national policies raise the overall level of labour market participation, they might create new social and labour market inequalities. This paper explores how institutional differences in the United Kingdom, Germany and Japan affect individual retirement decisions on the aggregate level, and variations in individuals’ degree of choice within and across countries. We investigate which groups of workers are disproportionately at risk of being ‘pushed’ out of employment, and how such inequalities have changed over time. We use comparable national longitudinal survey datasets focusing on the older population in England, Germany and Japan. Results point to cross-national differences in retirement transitions. Retirement transitions in Germany have occurred at an earlier age than in England and Japan. In Japan, the incidence of involuntary retirement is the lowest, reflecting an institutional context prescribing that employers provide employment until pension age, while Germany and England display substantial proportions of involuntary exits triggered by organisational-level redundancies, persistent early retirement plans or individual ill-health.

Optimal Route Search with the Coverage of Users' Preferences

The preferences of users are important in route search and planning. For example, when a user plans a trip within a city, their preferences can be expressed as keywords shopping mall, restaurant, and museum, with weights 0.5, 0.4, and 0.1, respectively. The resulting route should best satisfy their weighted preferences. In this paper, we take into account the weighted user preferences in route search, and present a keyword coverage problem, which finds an optimal route from a source location to a target location such that the keyword coverage is optimized and that the budget score satisfies a specified constraint. We prove that this problem is NP-hard. To solve this complex problem, we pro- pose an optimal route search based on an A* variant for which we have defined an admissible heuristic function. The experiments conducted on real-world datasets demonstrate both the efficiency and accu- racy of our proposed algorithms.

Chromatin immunoprecipitation (ChIP) methodology and readouts

The identification of direct nuclear hormone receptor gene targets provides clues to their contribution to both development and cancer progression. Until recently, the identification of such direct target genes has relied on a combination of expression analysis and in silico searches for consensus binding motifs in gene promoters. Consensus binding motifs for transcription factors are often defined using in vitro DNA binding strategies. Such in vitro strategies fail to account for the many factors that contribute significantly to target selection by transcription factors in cells beyond the recognition of these short consensus DNA sequences. These factors include DNA methylation, chromatin structure, posttranslational modifications of transcription factors, and the cooperative recruitment of transcription factor complexes. Chromatin immunoprecipitation (ChIP) provides a means of isolating transcription factor complexes in the context of endogenous chromatin, allowing the identification of direct transcription factor targets. ChIP can be combined with site-specific PCR for candidate binding sites or alternatively with cloning, genomic microarrays or more recently direct high throughput sequencing to identify novel genomic targets. The application of ChIP-based approaches has redefined consensus binding motifs for transcription factors and provided important insights into transcription factor biology.

Exodus? The training paths and plans of postgraduate medical trainees, under the Royal College of Physicians of Ireland

Background: In 2006, the Buttimer report highlighted the paucity of demographic data on those applying for and entering postgraduate medical education and training (PGMET) in Ireland. Today, concerns that there is an "exodus" of graduates of Irish medical schools are at the forefront of national discussion, however, published data on PGMET remains inadequate.

Aims: The objectives of this study were to collate existing data relating to trainees and training programmes at three stages of training and to examine the career plans of junior trainees.

Methods: Data from application forms for training programmes, commencing July 2012, under the Royal College of Physicians of Ireland (n = 870), were integrated with data from other existing sources. Candidates entering basic specialist training were surveyed with regard to career plans. Descriptive and comparative analysis was performed in SPSS version 18.

Results: Graduates of Irish medical schools made up over 70 % of appointees. Over 80 % of BST trainees aspired to work as consultants in Ireland, but 92.5 % planned to spend time working abroad (response rate 77 %). Decisions to leave the Irish system were linked to lifestyle, but also to failure to be appointed to higher specialist training. Significant numbers of trainees return to Ireland after a period abroad.

Conclusions: The trainee "exodus" is more complex than is often portrayed. The desire to spend time working outside Ireland must be accounted for in workforce planning and configuration of training programmes. Expansion of HST is a potential solution to reduce the numbers of graduates leaving Ireland post-BST.

Contribution of biobanks to care services

Approaches to the management of patients with cancer have been revolutionised by the ability to examine tumours at a genetic and molecular level and tailor treatments accordingly. Underpinning this work is the need for large numbers of high-quality human biospecimens for use in translational research studies to identify new biomarkers for the prediction, diagnosis and treatment of cancer. Biobanking has subsequently emerged as a dedicated activity to provide the infrastructure required for the standardised collection, storage and distribution of high quality human biospecimens for research purposes. This article provides an overview of the role of biobanks and the vital contribution they make to the delivery of cancer care for patients now and in the future

Predicting conversion to dementia in a memory clinic: A standard clinical approach compared with an empirically defined clustering method (latent profile analysis) for mild cognitive impairment subtyping

Introduction
Mild cognitive impairment (MCI) has clinical value in its ability to predict later dementia. A better understanding of cognitive profiles can further help delineate who is most at risk of conversion to dementia. We aimed to (1) examine to what extent the usual MCI subtyping using core criteria corresponds to empirically defined clusters of patients (latent profile analysis [LPA] of continuous neuropsychological data) and (2) compare the two methods of subtyping memory clinic participants in their prediction of conversion to dementia.

Methods
Memory clinic participants (MCI, n = 139) and age-matched controls (n = 98) were recruited. Participants had a full cognitive assessment, and results were grouped (1) according to traditional MCI subtypes and (2) using LPA. MCI participants were followed over approximately 2 years after their initial assessment to monitor for conversion to dementia.

Results
Groups were well matched for age and education. Controls performed significantly better than MCI participants on all cognitive measures. With the traditional analysis, most MCI participants were in the amnestic multidomain subgroup (46.8%) and this group was most at risk of conversion to dementia (63%). From the LPA, a three-profile solution fit the data best. Profile 3 was the largest group (40.3%), the most cognitively impaired, and most at risk of conversion to dementia (68% of the group).

Discussion
LPA provides a useful adjunct in delineating MCI participants most at risk of conversion to dementia and adds confidence to standard categories of clinical inference.

A Pension for Injured Victims of the Troubles: Reparations or Reifying Victim Hierarchy?

Reparations have been often used victim-centred measures to redress both private harm and gross violations of human rights. However, with the increasing occurrence of internal armed conflict and political violence, identities of victims and perpetrators in protracted conflicts can become blurred for some individuals. In countries like Peru and Northern Ireland that have suffered protracted violence, victimhood has been contested around which individuals are seen as innocent and deserving to exclude any members of non-state armed groups from claiming reparations. This article explores the issue of a proposed bill on a pension for injured victims of the Troubles in Northern Ireland. It identifies that there is no consistent state practice or human rights jurisprudence in this area, but instead offers a more complex approach through four models that can grapple with the seeming diametrically opposed victimhood and responsibility, by including victimised-perpetrators in reparations programmes such as that proposed for a pension of seriously injured victims in Northern Ireland.

Design and deployment of secure, robust, and resilient SDN Controllers

The scale of the Software-Defined Network (SDN) Controller design problem has become apparent with the expansion of SDN deployments. Initial SDN deployments were small-scale, single controller environments for research and usecase testing. Today, enterprise deployments requiring multiple controllers are gathering momentum e.g. Google’s backbone network, Microsoft’s public cloud, and NTT’s edge gateway. Third-party applications are also becoming available e.g. HP SDN App Store. The increase in components and interfaces for the evolved SDN implementation increases the security challenges of the SDN controller design. In this work, the requirements of a secure, robust, and resilient SDN controller are identified, stateof-the-art open-source SDN controllers are analyzed with respect to the security of their design, and recommendations for security improvements are provided. This contribution highlights the gap between the potential security solutions for SDN controllers and the actual security level of current controller designs.

Software defined FFT architecture for IEEE 802.11ac

The upcoming IEEE 802.11ac standard boosts the throughput of previous IEEE 802.11n by adding wider 80 MHz and 160 MHz channels with up to 8 antennas (versus 40 MHz channel and 4 antennas in 802.11n). This necessitates new 1-8 stream 256/512-point Fast Fourier Transform (FFT) / inverse FFT (IFFT) processing with 80/160 MSample/s throughput. Although there are abundant related work, they all fail to meet the requirements of IEEE 802.11ac FFT/IFFT on point size, throughput and multiple data streams at the same time. This paper proposes the first software defined FFT/IFFT architecture as a solution. By making use of a customised soft stream processor on FPGA, we show how a software defined FFT architecture can meet all the requirements of IEEE 802.11ac with low cost and high resource efficiency. When compared with dedicated Xilinx FFT core, our implementation exhibits only one third of the resources also up to three times of resource efficiency.

A biological survey method applied to seafloor massive sulphides (SMS) with contagiously distributed hydrothermal-vent fauna

Strategies for mitigation of seafloor massive sulphide (SMS) extraction in the deep sea include establishment of suitable reference sites that allow for studies of natural environmental variability and that can serve as sources of larvae for re-colonisation of extracted hydrothermal fields. In this study, we characterize deep-sea vent communities in Manus Basin (Bismarck Sea, Papua New Guinea) and use macrofaunal data sets from a proposed reference site (South Su) and a proposed mine site (Solwara 1) to test the hypothesis that there was no difference in macrofaunal community structure between the sites. We used dispersion weighting to adjust taxa-abundance matrices to down-weight the contribution of contagious distributions of numerically abundant taxa. Faunal assemblages of 3 habitat types defined by biogenic taxa (2 provannid snails, Alviniconcha spp. and Ifremeria nautilei; and a sessile barnacle, Eochionelasmus ohtai) were distinct from one another and from the vent peripheral assemblage, but were not differentiable from mound-to-mound within a site or between sites. Mussel and tubeworm populations at South Su but not at Solwara 1 enhance the taxonomic and habitat diversity of the proposed reference site. © Inter-Research 2012.

A HuGE Review and Meta-Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation

PURPOSE: New onset diabetes after transplantation (NODAT) is a serious complication following solid organ transplantation. There is a genetic contribution to NODAT and we have conducted comprehensive meta-analysis of available genetic data in kidney transplant populations.

METHODS: Relevant articles investigating the association between genetic markers and NODAT were identified by searching PubMed, Web of Science and Google Scholar. SNPs described in a minimum of three studies were included for analysis using a random effects model. The association between identified variants and NODAT was calculated at the per-study level to generate overall significance values and effect sizes.

RESULTS: Searching the literature returned 4,147 citations. Within the 36 eligible articles identified, 18 genetic variants from 12 genes were considered for analysis. Of these, three were significantly associated with NODAT by meta-analysis at the 5% level of significance; CDKAL1 rs10946398 p = 0.006 OR = 1.43, 95% CI = 1.11-1.85 (n = 696 individuals), KCNQ1 rs2237892 p = 0.007 OR = 1.43, 95% CI = 1.10-1.86 (n = 1,270 individuals), and TCF7L2 rs7903146 p = 0.01 OR = 1.41, 95% CI = 1.07-1.85 (n = 2,967 individuals).

CONCLUSION: Evaluating cumulative evidence for SNPs associated with NODAT in kidney transplant recipients has revealed three SNPs associated with NODAT. An adequately powered, dense genome-wide association study will provide more information using a carefully defined NODAT phenotype.

Cataract surgery and subtype in a defined, older population: the SEECAT Project

AIM:

To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals.

METHODS:

This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings).

RESULTS:

The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people.

CONCLUSION:

Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.

Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population.

PURPOSE:

To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population.

DESIGN:

Family-based cohort study.

PARTICIPANTS:

Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.

METHODS:

Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glaucoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.

MAIN OUTCOME MEASURES:

Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.

RESULTS:

We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, 0.35-0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).

CONCLUSIONS:

In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.