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.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II:Schizophrenia

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk

Prospective investigation of body mass index, colorectal adenoma, and colorectal cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection.

Detection of an outburst one year prior to the explosion of SN 2011ht

Using imaging from the Pan-STARRS1 survey, we identify a precursor outburst at epochs 287 and 170 days prior to the reported explosion of the purported Type IIn supernova (SN) 2011ht. In the Pan-STARRS data, a source coincident with SN 2011ht is detected exclusively in the \zps\ and \yps-bands. An absolute magnitude of M$_z\simeq$-11.8 suggests that this was an outburst of the progenitor star. Unfiltered, archival Catalina Real Time Transient survey images also reveal a coincident source from at least 258 to 138 days before the main event. We suggest that the outburst is likely to be an intrinsically red eruption, although we cannot conclusively exclude a series of erratic outbursts which were observed only in the redder bands by chance. This is only the fourth detection of an outburst prior to a claimed SN, and lends credence to the possibility that many more interacting transients have pre-explosion outbursts, which have been missed by current surveys.

A lesson in business: cost-effectiveness analysis of a novel financial incentive intervention for increasing physical activity in the workplace

Background: Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer’s perspective.

Methods: Employees used a ‘loyalty card’ to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates.

Results: The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds.

Conclusions: The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer’s perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable “business model” which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges.

Politically sensitive encounters: Ethnography, access and the benefits of ‘hanging out’

Negotiating politically sensitive research environments requires both a careful consideration of the methods involved, and a great deal of personal resolve. In drawing upon two distinct yet comparable fieldwork experiences this paper champions the benefits of ethnographic methods in seeking to gain positionality and research legitimacy amongst those identified as future research participants. The authors explore and discuss their use of the ethnographic concept of ‘hanging out’ in politically sensitive environments when seeking to negotiate access to potentially hard to reach participants living in challenging research environments. Through an illustrative examination of their experiences in researching commemorative rituals in Palestine and mental health in a Northern Irish prison, both authors reflect upon their use of hanging out when seeking to break down barriers and gain acceptance amongst their target research participants. Their involvement in a range of activities, not directly related to the overall aims of the research project, highlight a need for qualitative researchers to adopt a flexible research design, one that embraces serendipitous or chance encounters, when seeking to gain access to hard to reach research participants or when issues of researcher legitimacy are particularly pronounced such as is the case in politically sensitive research environments.

Auditory gist: Recognition of very short sounds from timbre cues

Sounds such as the voice or musical instruments can be recognized on the basis of timbre alone. Here, sound recognition was investigated with severely reduced timbre cues. Short snippets of naturally recorded sounds were extracted from a large corpus. Listeners were asked to report a target category (e.g., sung voices) among other sounds (e.g., musical instruments). All sound categories covered the same pitch range, so the task had to be solved on timbre cues alone. The minimum duration for which performance was above chance was found to be short, on the order of a few milliseconds, with the best performance for voice targets. Performance was independent of pitch and was maintained when stimuli contained less than a full waveform cycle. Recognition was not generally better when the sound snippets were time-aligned with the sound onset compared to when they were extracted with a random starting time. Finally, performance did not depend on feedback or training, suggesting that the cues used by listeners in the artificial gating task were similar to those relevant for longer, more familiar sounds. The results show that timbre cues for sound recognition are available at a variety of time scales, including very short ones.

Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data

Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature.

The effect of choice on motivation for young children on the autism spectrum during discrete trial teaching

Self-determination and decision-making are acknowledged internationally as key rights of persons with disabilities and should play an important role in the development of educational plans and procedures. Not only is the chance for individuals with developmental disabilities to select their own tasks, leisure activities or reinforcers a valuable way of enhancing rights-based education and personal dignity, but choice-making opportunities may also function as a useful clinical or educational tool if they actually improve the efficacy of programmes aimed at the acquisition of socially relevant behaviours and life skills or the reduction of challenging behaviours.

The study reported here assessed whether or not choice affected effectiveness of an educational procedure for three children on the autism spectrum. Following a preference assessment, a number of discrete teaching trials were conducted with each child and, contingent upon targeted responses, either the child or the therapist selected one of three preferred reinforcer items. Reinforcer choice did not affect intervention effectiveness for two of the children; however, performance and motivation improved for the third child. Results re-affirmed the importance of thorough preference assessments prior to intervention and showed that additional stimulus choice contingent on the target response may improve motivation and outcomes for some children.

Processing of short auditory stimuli:The rapid audio sequential presentation paradigm (RASP)

Human listeners seem to be remarkably able to recognise acoustic sound sources based on timbre cues. Here we describe a psychophysical paradigm to estimate the time it takes to recognise a set of complex sounds differing only in timbre cues: both in terms of the minimum duration of the sounds and the inferred neural processing time. Listeners had to respond to the human voice while ignoring a set of distractors. All sounds were recorded from natural sources over the same pitch range and equalised to the same duration and power. In a first experiment, stimuli were gated in time with a raised-cosine window of variable duration and random onset time. A voice/non-voice (yes/no) task was used. Performance, as measured by d', remained above chance for the shortest sounds tested (2 ms); d's above 1 were observed for durations longer than or equal to 8 ms. Then, we constructed sequences of short sounds presented in rapid succession. Listeners were asked to report the presence of a single voice token that could occur at a random position within the sequence. This method is analogous to the "rapid sequential visual presentation" paradigm (RSVP), which has been used to evaluate neural processing time for images. For 500-ms sequences made of 32-ms and 16-ms sounds, d' remained above chance for presentation rates of up to 30 sounds per second. There was no effect of the pitch relation between successive sounds: identical for all sounds in the sequence or random for each sound. This implies that the task was not determined by streaming or forward masking, as both phenomena would predict better performance for the random pitch condition. Overall, the recognition of familiar sound categories such as the voice seems to be surprisingly fast, both in terms of the acoustic duration required and of the underlying neural time constants.

Search protocols for hidden forensic objects beneath floors and within walls

The burial of objects (human remains, explosives, weapons) below or behind concrete, brick, plaster or tiling may be associated with serious crime and are difficult locations to search. These are quite common forensic search scenarios but little has been published on them to-date. Most documented discoveries are accidental or from suspect/witness testimony. The problem in locating such hidden objects means a random or chance-based approach is not advisable. A preliminary strategy is presented here, based on previous studies, augmented by primary research where new technology or applications are required. This blend allows a rudimentary search workflow, from remote desktop study, to non-destructive investigation through to recommendations as to how the above may inform excavation, demonstrated here with a case study from a homicide investigation. Published case studies on the search for human remains demonstrate the problems encountered when trying to find and recover sealed-in and sealed over locations. Established methods include desktop study, photography, geophysics and search dogs:these are integrated with new technology (LiDAR and laser scanning; photographic rectification; close quarter aerial imagery; ground-penetrating radar on walls and gamma-ray/neutron activation radiography) to propose this possible search strategy.

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(^-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Determinants of root-associated fungal communities within Asteraceae in a semi-arid grassland

Summary

1.While plant–fungal interactions are important determinants of plant community assembly and ecosystem functioning, the processes underlying fungal community composition are poorly understood.
2.Here, we studied for the first time the root-associated eumycotan communities in a set of co-occurring plant species of varying relatedness in a species-rich, semi-arid grassland in Germany. The study system provides an opportunity to evaluate the importance of host plants and gradients in soil type and landscape structure as drivers of fungal community structure on a relevant spatial scale. We used 454 pyrosequencing of the fungal internal transcribed spacer region to analyse root-associated eumycotan communities of 25 species within the Asteraceae, which were sampled at different locations within a soil type gradient. We partitioned the variance accounted for by three predictors (host plant phylogeny, spatial distribution and soil type) to quantify their relative roles in determining fungal community composition and used null model analyses to determine whether community composition was influenced by biotic interactions among the fungi.
3.We found a high fungal diversity (156 816 sequences clustered in 1100 operational taxonomic units (OTUs)). Most OTUs belonged to the phylum Ascomycota (35.8%); the most abundant phylotype best-matched Phialophora mustea. Basidiomycota were represented by 18.3%, with Sebacina as most abundant genus. The three predictors explained 30% of variation in the community structure of root-associated fungi, with host plant phylogeny being the most important variance component. Null model analysis suggested that many fungal taxa co-occurred less often than expected by chance, which demonstrates spatial segregation and indicates that negative interactions may prevail in the assembly of fungal communities.
4.Synthesis. The results show that the phylogenetic relationship of host plants is the most important predictor of root-associated fungal community assembly, indicating that fungal colonization of host plants might be facilitated by certain plant traits that may be shared among closely related plant species.

Pseudomonas aeruginosa exhibits frequent recombination, but only a limited association between genotype and ecological setting

Pseudomonas aeruginosa is an opportunistic pathogen and an important cause of infection, particularly amongst cystic fibrosis (CF) patients. While specific strains capable of patient-to-patient transmission are known, many infections appear to be caused by unique and unrelated strains. There is a need to understand the relationship between strains capable of colonising the CF lung and the broader set of P. aeruginosa isolates found in natural environments. Here we report the results of a multilocus sequence typing (MLST)-based study designed to understand the genetic diversity and population structure of an extensive regional sample of P. aeruginosa isolates from South East Queensland, Australia. The analysis is based on 501 P. aeruginosa isolates obtained from environmental, animal and human (CF and non-CF) sources with particular emphasis on isolates from the Lower Brisbane River and isolates from CF patients obtained from the same geographical region. Overall, MLST identified 274 different sequence types, of which 53 were shared between one or more ecological settings. Our analysis revealed a limited association between genotype and environment and evidence of frequent recombination. We also found that genetic diversity of P. aeruginosa in Queensland, Australia was indistinguishable from that of the global P. aeruginosa population. Several CF strains were encountered frequently in multiple ecological settings; however, the most frequently encountered CF strains were confined to CF patients. Overall, our data confirm a non-clonal epidemic structure and indicate that most CF strains are a random sample of the broader P. aeruginosa population. The increased abundance of some CF strains in different geographical regions is a likely product of chance colonisation events followed by adaptation to the CF lung and horizontal transmission among patients.