Decreased respiratory system compliance on the sixth day of mechanical ventilation is a predictor of death in patients with established acute lung injury

Background: Multiple studies have identified single variables or composite scores that help risk stratify patients at the time of acute lung injury (ALI) diagnosis. However, few studies have addressed the important question of how changes in pulmonary physiologic variables might predict mortality in patients during the subacute or chronic phases of ALI. We studied pulmonary physiologic variables, including respiratory system compliance, P/F ratio and oxygenation index, in a cohort of patients with ALI who survived more than 6 days of mechanical ventilation to see if changes in these variables were predictive of death and whether they are informative about the pathophysiology of subacute ALI.

Evaluating Train Protection Systems

This paper arose from the work carried out for the Cullen/Uff Joint Inquiry into Train Protection Systems. It is concerned with the problem of evaluating the benefits of safety enhancements in order to avoid rare, but catastrophic accidents, and the role of Operations Research in the process. The problems include both input values and representation of outcomes. A key input is the value of life. This paper briefly discusses why the value of life might vary from incident to incident and reviews alternative estimates before producing a 'best estimate' for rail. When the occurrence of an event is uncertain, the normal method is to apply a single 'expected' value. This paper argues that a more effective method of representing such situations is through Monte-Carlo simulation and demonstrates the use of the methodology on a case study of the decision as to whether or not advanced train protection (ATP) should have been installed on a route to the west of London. This paper suggests that the output is more informative than traditional cost-benefit appraisals or engineering event tree approaches. It also shows that, unlike the results from utilizing the traditional approach, the value of ATP on this route would be positive over 50% of the time.

Flexible paleoclimate age-depth models using an autoregressive gamma process

Radiocarbon dating is routinely used in paleoecology to build chronolo- gies of lake and peat sediments, aiming at inferring a model that would relate the sediment depth with its age. We present a new approach for chronology building (called “Bacon”) that has received enthusiastic attention by paleoecologists. Our methodology is based on controlling core accumulation rates using a gamma autoregressive semiparametric model with an arbitrary number of subdivisions along the sediment. Using prior knowledge about accumulation rates is crucial and informative priors are routinely used. Since many sediment cores are currently analyzed, using different data sets and prior distributions, a robust (adaptive) MCMC is very useful. We use the t-walk (Christen and Fox, 2010), a self adjusting, robust MCMC sampling algorithm, that works acceptably well in many situations. Outliers are also addressed using a recent approach that considers a Student-t model for radiocarbon data. Two examples are presented here, that of a peat core and a core from a lake, and our results are compared with other approaches.

Real-life Social Attention in Children with Autism Spectrum Disorders

Autism is a neuro-developmental disorder defined by atypical social behaviour, of which atypical social attention behaviours are among the earliest clinical markers (Volkmar et al., 1997). Eye tracking studies using still images and movie clips have provided a method for the precise quantification of atypical social attention in ASD. This is generally characterised by diminished viewing of the most socially pertinent regions (eyes), and increased viewing of less socially informative regions (body, background, objects) (Klin et al., 2002; Riby & Hancock, 2008, 2009). Ecological validity within eye tracking studies has become an increasingly important issue. As of yet, however, little is known about the precise nature of the atypicalities of social attention in ASD in real-life. Objectives: To capture and quantify gaze patterns for children with an ASD within a real life setting, compared to two Typically Developing (TD) comparison groups. Methods: Nine children with an ASD were compared to two age matched TD groups – a verbal (N=9) and a non-verbal (N=9) comparison group. A real-life scenario was created involving an experimenter posing as a magician, and consisted of 3 segments: a conversation segment; a magic trick segment; and a puppet segment. The first segment explored children’s attentional preferences during a real-life conversation; the magic trick segment explored children’s use of the eyes as a communicative cue, and the puppet segment explored attention capture. Finally, part of the puppet section explored children’s use of facial information in response to an unexpected event. Results: The most striking difference between the groups was the diminished viewing of the eyes by the ASD group in comparison to both control groups. This was found particularly during the conversation segment, but also during the magic trick segment, and during the puppet segment. When in conversation, participants with ASD were found to spend a greater proportion time looking off-screen, in comparison to TD participants. There was also a tendency for the ASD group to spend a greater proportion of time looking to the mouth of the experimenter. During the magic trick segment, despite the fact that the eyes were not predictive of a correct location, both TD comparison groups continued to use the eyes as a communicative cue, whereas the ASD group did not. In the puppet segment, all three groups spent a similar amount of time looking between the puppet and regions of the experimenter’s face. However, in response to an unexpected event, the ASD group were significantly slower to fixate back on the experimenter’s face. Conclusions: The results demonstrate the reduced salience of socially pertinent information for children with ASD in real life, and they provide support for the findings from previous eye tracking studies involving scene viewing. However, the results also highlight a pattern looking off-screen for both the TD and ASD groups. This eye movement behaviour is likely to be associated specifically with real-life interaction, as it has functional relevance (Doherty-Sneddon et al., 2002). However, the fact that it is significantly increased in the ASD group has implications for their understanding of real life social interactions.

Exploring Scale Effects of Best/Worst Rank Ordered Choice Data to Estimate Benefits of Tourism in Alpine Grazing Commons

In many environmental valuation applications standard sample sizes for choice modelling surveys are impractical to achieve. One can improve data quality using more in-depth surveys administered to fewer respondents. We report on a study using high quality rank-ordered data elicited with the best-worst approach. The resulting "exploded logit" choice model, estimated on 64 responses per person, was used to study the willingness to pay for external benefits by visitors for policies which maintain the cultural heritage of alpine grazing commons. We find evidence supporting this approach and reasonable estimates of mean WTP, which appear theoretically valid and policy informative. © The Author (2011).

Association analysis of proopiomelanocortin (POMC) haplotypes in type 1 diabetes in a UK population

Aim

To assess the association of POMC haplotype-tagged single nucleotide polymorphisms (htSNPs) with the development of type 1 diabetes (T1D) in a Caucasian population.

Methods

All exons, intron 1, and approximately 6-kb upstream and 3-kb downstream of the POMC gene were bidirectionally resequenced to identify DNA polymorphisms in 30 individuals. Allele frequencies were determined (60 chromosomes) and efficient htSNPs were selected using the htSNP2 programme. Genotyping was performed in 390 cases, 339 controls and 245 T1D parent-offspring trios, using Taqman, Sequenom and direct-sequencing technologies.

Results

Thirteen polymorphisms (two novel) with a minor allele frequency greater than 1% were identified. Six POMC htSNPs (rs3754863 G>A, ss161151662 A>G, rs3754860 C>T, rs1009388 G>C, rs3769671 A>C, rs1042571 G>A) were identified. Allele and haplotype frequencies were similar between case and control groups (P>0.60 by permutation test), and assessment of allele transmission distortion from informative parents to affected offspring also failed to find any association. Stratification of these analyses for age-at-onset and HLA-DR risk group (DR3/DR4) revealed no significant associations. A haplotype block of 9.86-kb from rs3754863 to rs1042571 was identified, encompassing the POMC gene. Comparison of haplotype frequencies identified the GGCGAG haplotype as protective against T1D in 12.9% of cases vs. 18.3% of controls: ?2=8.18, Pc=0.03 by permutation test.

Conclusion

The POMC SNP haplotype GGCGAG may have a protective effect against T1D in the UK population. However, this finding needs to be replicated, and the cellular and molecular processes influenced by this POMC haplotype determined to fully appreciate its impact.

Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1615 affected and 1602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5861 single nucleotide polymorphisms (SNPs; Illumina version 4.0 linkage map). Suggestive evidence for linkage ( European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in nonparametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-LOD support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region. Molecular Psychiatry (2009) 14, 786-795; doi:10.1038/mp.2009.11; published online 17 February 2009

Recurrence of Urothelial Carcinoma of the Bladder: A Role for Insulin-Like Growth Factor-II Loss of Imprinting and Cytoplasmic E-Cadherin Immunolocalization

Purpose:This study documents the frequency of insulin-like growth factor-II (IGF-II) loss of imprinting (LOI) in a series of 87 bladder tissues. E-cadherin (CDH1) immunolocalization was also investigated due to the known redistribution of this adherence protein to the cytoplasm following exogenous exposure to IGF-II.
Experimental Design: Informative IGF-II cases were identified following DNA-PCR amplification and subsequent sequencing of the transcribable ApaI RFLP in exon 9 of IGF-II. Similar approaches using primer-specific cDNA templates identified the imprinting status of IGF-II in these informative cases. CDH1cellular localization was assessed on a tissue microarray platform of 114 urothelial carcinoma of the bladder (UCB) cases (70 pTanoninvasive and 44 pT1laminapropria invasive) using the commercially available Novocastra antibody.
Results: IGF-IILOI was evident in 7 of17 (41%) UCB tumors and 4 of11 (36%) tumor-associated normal urothelial samples.Two of four pT1grade 3 tumors, the subject of much debate concerning their suitability for radical cystectomy, showed LOI at the IGF-II locus. In those tumors showing IGF-II LOI, 4 of 7 (57%) displayed concomitant CDH1cytoplasmic staining. In contrast, only 3 of 10 (30%) IGF-IImaintenance ofimprinting tumorshad concomitant CDH1cytoplasmiclocalization. UCB cell lines displaying cytoplasmic CDH1immunolocalization expressed significantly higher levels of IGF-II (CAL29, HT1376, and RT112) compared with RT4, a cell line displaying crisp membranous CDH1staining. Finally, cytoplasmic CDH1staining was an independent predictor of a shorter time to recurrence independent of tumor grade and stage.
Conclusions: We suggest that CDH1 cytoplasmic immunolocalization as a result of increased IGF-II levels identifies those nonmuscle invasive presentations most likely to recur and therefore might benefit from more radical nonconserving bladder surgery

The development of effective biomarkers for Alzheimer's disease:a review

OBJECTIVE: There is a widely recognised need to develop effective Alzheimer's disease (AD) biomarkers to aid the development of disease-modifying treatments, to facilitate early diagnosis and to improve clinical care. This overview aims to summarise the utility of key neuroimaging and cerebrospinal fluid (CSF) biomarkers for AD, before focusing on the latest efforts to identify informative blood biomarkers. DESIGN: A literature search was performed using PubMed up to September 2011 for reviews and primary research studies of neuroimaging (magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography and amyloid imaging), CSF and blood-based (plasma, serum and platelet) biomarkers in AD and mild cognitive impairment. Citations within individual articles were examined to identify additional studies relevant to this review. RESULTS: Evidence of AD biomarker potential was available for imaging techniques reflecting amyloid burden and neurodegeneration. Several CSF measures are promising, including 42 amino acid ß-amyloid peptide (Aß(42) ); total tau (T-tau) protein, reflecting axonal damage; and phosphorylated tau (P-tau), reflecting neurofibrillary tangle pathology. Studies of plasma Aß have produced inferior diagnostic discrimination. Alternative plasma and platelet measures are described, which represent potential avenues for future research. CONCLUSIONS: Several imaging and CSF markers demonstrate utility in predicting AD progression and determining aetiology. These require standardisation before forming core elements of diagnostic criteria. The enormous potential available for identifying a minimally-invasive, easily-accessible blood measure as an effective AD biomarker currently remains unfulfilled. Copyright © 2012 John Wiley & Sons, Ltd.

Possible association between CTLA4 DNA polymorphisms and early onset type 1 diabetes in a UK population

Linkage and association has been reported between CTLA4 DNA markers and susceptibility to type 1 diabetes in some populations, but not others. We performed case-control and family-based association studies to assess if the CTLA4 A49G and intron 1 C/T polymorphisms were associated with development of early onset type 1 diabetes in the Northern Ireland population. The distribution of A49G and C/T alleles in cases (n = 144) was similar to those observed in controls (n = 307). In contrast, significant distortions in allele transmissions from informative parents to probands were observed for both the A49G (P = 0.02) and C/T (P = 0.01) polymorphisms employing 297 nuclear families. Our results suggest that the CTLA4 gene may play a minor role in the overall genetic predisposition to type 1 diabetes in this UK population.

Substantial genetic divergence between morphologically indistinguishable populations of Fasciola suggests the possibility of cryptic speciation.

The liver flukes, Fasciola hepatica and Fasciola gigantica, are considered to be sister species and between them present a major threat worldwide to livestock production. In this study sequence data have been employed from informative regions of the nuclear and mitochondrial genomes of over 200 morphologically F. hepatica-like or F. gigantica-like flukes from Europe, sub-Saharan Africa and South Asia to assess genetic diversity. Evidence is presented for the existence of four well-separated clades: African gigantica-like flukes, Indian gigantica-like flukes, European hepatica-like flukes and African high-altitude hepatica-like flukes. Application of the Biological Species Concept to trematodes is problematic; however, the degree of separation between these groups was sufficient for them to be considered as distinct species using the four times rule for speciation.

Making geography mobile: using location aware technology to improve student performance in physical geography

With the increased availability of new technologies, geography educators are revisiting their pedagogical approaches to teaching and calling for opportunities to share local and international practices which will enhance the learning experience and improve students’ performance. This paper reports on the use of handheld mobile devices, fitted with GPS, by secondary (high) school pupils in geography. Two location-aware activities were completed over one academic year (one per semester) and pre-test and post-test scores for both topics revealed a statistically significant increase in pupils’ performance as measured by the standard national assessments. A learner centred educational approach was adopted with the first mobile learning activity being created by the teacher as an exemplar of effective mobile learning design. Pupils built on their experiences of using mobile learning when they were required to created their own location aware learning task for peer use. An analysis of the qualitative data from the pupils’ journals, group diaries and focus group interviews revealed the five pillars of learner centred education are addressed when using location aware technologies and the use of handheld mobile devices offered greater flexibility and autonomy to the pupils thus altering the level of power and control away from the teacher. Due to the relatively small number of participants in the study, the results are more informative than generalisable however in light of the growing interest in geo-spatial technologies in geography education, this paper offers encouragement and insight into the use of location aware technology in a compulsory school context

EEG decoding of semantic category reveals distributed representations for single concepts

Achieving a clearer picture of categorial distinctions in the brain is essential for our understanding of the conceptual lexicon, but much more fine-grained investigations are required in order for this evidence to contribute to lexical research. Here we present a collection of advanced data-mining techniques that allows the category of individual concepts to be decoded from single trials of EEG data. Neural activity was recorded while participants silently named images of mammals and tools, and category could be detected in single trials with an accuracy well above chance, both when considering data from single participants, and when group-training across participants. By aggregating across all trials, single concepts could be correctly assigned to their category with an accuracy of 98%. The pattern of classifications made by the algorithm confirmed that the neural patterns identified are due to conceptual category, and not any of a series of processing-related confounds. The time intervals, frequency bands and scalp locations that proved most informative for prediction permit physiological interpretation: the widespread activation shortly after appearance of the stimulus (from 100. ms) is consistent both with accounts of multi-pass processing, and distributed representations of categories. These methods provide an alternative to fMRI for fine-grained, large-scale investigations of the conceptual lexicon. © 2010 Elsevier Inc.

Determinants of WTP for Prosecco wine: A latent class regression with attitudinal responses

Purpose – Under investigation is Prosecco wine, a sparkling white wine from North-East Italy.
Information collection on consumer perceptions is particularly relevant when developing market
strategies for wine, especially so when local production and certification of origin play an important
role in the wine market of a given district, as in the case at hand. Investigating and characterizing the
structure of preference heterogeneity become crucial steps in every successful marketing strategy. The
purpose of this paper is to investigate the sources of systematic differences in consumer preferences.
Design/methodology/approach – The paper explores the effect of inclusion of answers to
attitudinal questions in a latent class regression model of stated willingness to pay (WTP) for this
specialty wine. These additional variables were included in the membership equations to investigate
whether they could be of help in the identification of latent classes. The individual specific WTPs from
the sampled respondents were then derived from the best fitting model and examined for consistency.
Findings – The use of answers to attitudinal question in the latent class regression model is found to
improve model fit, thereby helping in the identification of latent classes. The best performing model
obtained makes use of both attitudinal scores and socio-economic covariates identifying five latent
classes. A reasonable pattern of differences in WTP for Prosecco between CDO and TGI types were
derived from this model.
Originality/value – The approach appears informative and promising: attitudes emerge as
important ancillary indicators of taste differences for specialty wines. This might be of interest per se
and of practical use in market segmentation. If future research shows that these variables can be of use
in other contexts, it is quite possible that more attitudinal questions will be routinely incorporated in
structural latent class hedonic models.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.