mzML--a community standard for mass spectrometry data.

Mass spectrometry is a fundamental tool for discovery and analysis in the life sciences. With the rapid advances in mass spectrometry technology and methods, it has become imperative to provide a standard output format for mass spectrometry data that will facilitate data sharing and analysis. Initially, the efforts to develop a standard format for mass spectrometry data resulted in multiple formats, each designed with a different underlying philosophy. To resolve the issues associated with having multiple formats, vendors, researchers, and software developers convened under the banner of the HUPO PSI to develop a single standard. The new data format incorporated many of the desirable technical attributes from the previous data formats, while adding a number of improvements, including features such as a controlled vocabulary with validation tools to ensure consistent usage of the format, improved support for selected reaction monitoring data, and immediately available implementations to facilitate rapid adoption by the community. The resulting standard data format, mzML, is a well tested open-source format for mass spectrometer output files that can be readily utilized by the community and easily adapted for incremental advances in mass spectrometry technology.

Learning new faces in typical and atypical populations of children.

Recognizing an individual as familiar is an important aspect of our social cognition, which requires both learning a face and recalling it. It has been suggested that children with autistic spectrum disorder (ASD) have deficits and abnormalities in face processing. We investigated whether the process by which unfamiliar faces become familiar differs in typically developing (TD) children, children with ASD, and children with developmental delay. Children were familiarized with a set of moving novel faces presented over a three-day period. Recognition of the learned faces was assessed at five time points during the three-day period. Both immediate and delayed recall of faces was tested. All groups showed improvements in face recognition at immediate recall, which indicated that learning had occurred. The TD population showed slightly better performance than the two other groups, however no difference was specific to the ASD group. All groups showed similar levels of improvements with time. Our results are discussed in terms of learning in ASD.

Incorporating new approach methodologies into regulatory nonclinical pharmaceutical safety assessment.

New approach methodologies (NAMs) based on human biology enable the assessment of adverse biological effects of pharmaceuticals and other chemicals. Currently, however, it is unclear how NAMs should be used during drug development to improve human safety evaluation. A series of 5 workshops with 13 international experts (regulators, preclinical scientists, and NAMs developers) was conducted to identify feasible NAMs and to discuss how to exploit them in specific safety assessment contexts. Participants generated four "maps" of how NAMs can be exploited in the safety assessment of the liver, respiratory, cardiovascular, and central nervous systems. Each map shows relevant endpoints measured and tools used (e.g., cells, assays, platforms), and highlights gaps where further development and validation of NAMs remains necessary. Each map addresses the fundamental scientific requirements for the safety assessment of that organ system, providing users with guidance on the selection of appropriate NAMs. In addition to generating the maps, participants offered suggestions for encouraging greater NAM adoption within drug development and their inclusion in regulatory guidelines. A specific recommendation was that pharmaceutical companies should be more transparent about how they use NAMs in-house. As well as giving guidance for the four organ systems, the maps provide a template that could be used for additional organ safety testing contexts. Moreover, their conversion to an interactive format would enable users to drill down to the detail necessary to answer specific scientific and regulatory questions.

Development of motion processing in children with autism.

Recent findings suggest that children with autism may be impaired in the perception of biological motion from moving point-light displays. Some children with autism also have abnormally high motion coherence thresholds. In the current study we tested a group of children with autism and a group of typically developing children aged 5 to 12 years of age on several motion perception tasks, in order to establish the specificity of the biological motion deficit in relation to other visual discrimination skills. The first task required the recognition of biological from scrambled motion. Three quasi-psychophysical tasks then established individual thresholds for the detection of biological motion in dynamic noise, of motion coherence and of form-from-motion. Lastly, individual thresholds for a task of static perception--contour integration (Gabor displays)--were also obtained. Compared to controls, children with autism were particularly impaired in processing biological motion in relation to any developmental measure (chronological or mental age). In contrast, there was some developmental overlap in ability to process other types of visual motion between typically developing children and the children with autism, and evidence of developmental change in both groups. Finally, Gabor display thresholds appeared to develop typically in children with autism.

Selective attention and perceptual load in autism spectrum disorder.

It has been suggested that the locus of selective attention (early vs. late in processing) is dependent on the perceptual load of the task. When perceptual load is low, irrelevant distractors are processed (late selection), whereas when perceptual load is high, distractor interference disappears (early selection). Attentional abnormalities have long been reported within autism spectrum disorder (ASD), and this study is the first to examine the effect of perceptual load on selective attention in this population. Fourteen adults with ASD and 23 adults without ASD performed a selective attention task with varying perceptual loads. Compared with the non-ASD group, the ASD group required higher levels of perceptual load to successfully ignore irrelevant distractors; moreover, the ASD group did not show any general reduction in performance speed or accuracy. These results suggest enhanced perceptual capacity in the ASD group and are consistent with previous observations regarding superior visual search abilities among individuals with ASD.

Assessing speech perception in young children and relationships with language skills.

Few materials are available to assess speech perceptual skills in young children without hearing impairments. However, children with a range of developmental conditions are at risk of speech discrimination deficits. Tasks that reliably assess speech perception skills are thus necessary for research and clinical practice. The development and application of two speech perception tests are described. Data were collected from 105 children, aged 4-5 years, attending mainstream schools, on two tasks, mispronunciation detection and non-word XAB, in quiet and in a background of multi-talker babble. Children's receptive language skills were also measured. Performance on mispronunciation detection was significantly better than on the XAB non-word task, and significantly better in quiet than in babble. Performance significantly improved with age, and speech discrimination was significantly related to receptive language abilities. Scores obtained in quiet and in babble were highly correlated and findings suggest there may be no advantage to testing in noise, except to avoid ceiling effects on performance. These tasks prove useful in the assessment of young children who may have speech discrimination deficits.

Multi-site harmonization of diffusion MRI data in a registration framework.

Diffusion MRI (dMRI) data acquired on different scanners varies significantly in its content throughout the brain even if the acquisition parameters are nearly identical. Thus, proper harmonization of such data sets is necessary to increase the sample size and thereby the statistical power of neuroimaging studies. In this paper, we present a novel approach to harmonize dMRI data (the raw signal, instead of dMRI derived measures such as fractional anisotropy) using rotation invariant spherical harmonic (RISH) features embedded within a multi-modal image registration framework. All dMRI data sets from all sites are registered to a common template and voxel-wise differences in RISH features between sites at a group level are used to harmonize the signal in a subject-specific manner. We validate our method on diffusion data acquired from seven different sites (two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across these sites before and after data harmonization. Validation was also done on a group oftest subjects, which were not used to "learn" the harmonization parameters. We also show results using TBSS before and after harmonization for independent validation of the proposed methodology. Using synthetic data, we show that any abnormality in diffusion measures due to disease is preserved during the harmonization process. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences in the signal can be removed using the proposed method in a model independent manner.

Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1.

The ECM protein Del-1 is one of several novel ECM proteins that accumulate around angiogenic blood vessels in embryonic and tumor tissue and promote angiogenesis in the absence of exogenous growth factors. Del-1 expressed in mouse or rabbit ischemic hind-limb muscle by gene transfer rapidly promotes new blood vessel formation and restores muscle function. This angiogenic ECM protein initiates angiogenesis by binding to integrin alphavbeta5 on resting endothelium, thereby resulting in expression of the transcription factor Hox D3 and integrin alphavbeta3. Hox D3 converts resting endothelium to angiogenic endothelium by inducing expression of proangiogenic molecules such as integrin alphavbeta3. These findings provide evidence for an angiogenic switch that can be initiated in the absence of exogenous growth factors and indicate that the angiogenic matrix protein Del-1 may be a useful tool for the therapy of ischemic disease.

Perception of pointing from biological motion point-light displays in typically developing children and children with autism spectrum disorder.

We examined whether the movement involved in a pointing gesture, depicted using point-light displays, is sufficient to cue attention in typically developing children (TD) and children with autism spectrum disorder (ASD) (aged 8-11 years). Using a Posner-type paradigm, a centrally located display indicated the location of a forthcoming target on 80% of trials and the opposite location on 20% of trials. TD children, but not children with ASD, were faster to identify a validly cued target than an invalidly cued target. A scrambled version of the point-light pointing gesture, retaining individual dot speed and direction of movement but not the configuration, produced no validity effect in either group. A video of a pointing gesture produced validity effects in both groups.

Speechreading development in deaf and hearing children: introducing the test of child speechreading.

PURPOSE: In this article, the authors describe the development of a new instrument, the Test of Child Speechreading (ToCS), which was specifically designed for use with deaf and hearing children. Speechreading is a skill that is required for deaf children to access the language of the hearing community. ToCS is a deaf-friendly, computer-based test that measures child speechreading (silent lipreading) at 3 psycholinguistic levels: (a) Words, (b) Sentences, and (c) Short Stories. The aims of the study were to standardize the ToCS with deaf and hearing children and to investigate the effects of hearing status, age, and linguistic complexity on speechreading ability. METHOD: Eighty-six severely and profoundly deaf children and 91 hearing children participated. All children were between the ages of 5 and 14 years. The deaf children were from a range of language and communication backgrounds, and their preferred mode of communication varied. RESULTS: Speechreading skills significantly improved with age for both groups of children. There was no effect of hearing status on speechreading ability, and children from both groups showed similar performance across all subtests of the ToCS. CONCLUSION: The ToCS is a valid and reliable assessment of speechreading ability in school-age children that can be used to measure individual differences in performance in speechreading ability.

Young children with autism spectrum disorder do not preferentially attend to biological motion.

Preferential attention to biological motion can be seen in typically developing infants in the first few days of life and is thought to be an important precursor in the development of social communication. We examined whether children with autism spectrum disorder (ASD) aged 3-7 years preferentially attend to point-light displays depicting biological motion. We found that children with ASD did not preferentially attend to biological motion over phase-scrambled motion, but did preferentially attend to a point-light display of a spinning top rather than a human walker. In contrast a neurotypical matched control group preferentially attended to the human, biological motion in both conditions. The results suggest a core deficit in attending to biological motion in ASD.

High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS versus increased risks due to pig-keeping and house construction.

BACKGROUND: African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed. METHODS: Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1-15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed. RESULTS: Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%-57.1%) in children 1-15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%-27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%-77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR)= 0.6; 95%CI: 0.4-0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3-0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5-0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0-1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1-4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3-2.4) versus other roofing materials and bigger household size (8-15 people: OR = 1.6; 95%CI: 1.3-2.1) versus small households (1-4 persons). CONCLUSION: Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs.

How much does malaria vector control quality matter: the epidemiological impact of holed nets and inadequate indoor residual spraying.

BACKGROUND: Insecticide treated nets (ITN) and indoor residual spraying (IRS) are the two pillars of malaria vector control in Africa, but both interventions are beset by quality and coverage concerns. Data from three control programs were used to investigate the impact of: 1) the physical deterioration of ITNs, and 2) inadequate IRS spray coverage, on their respective protective effectiveness. METHODS: Malaria indicator surveys were carried out in 2009 and 2010 in Bioko Island, mainland Equatorial Guinea and Malawi to monitor infection with P. falciparum in children, mosquito net use, net condition and spray status of houses. Nets were classified by their condition. The association between infection and quality and coverage of interventions was investigated. RESULTS: There was reduced odds of infection with P. falciparum in children sleeping under ITNs that were intact (Odds ratio (OR): 0.65, 95% CI: 0.55-0.77 and OR: 0.81, 95% CI: 0.56-1.18 in Equatorial Guinea and in Malawi respectively), but the protective effect became less with increasingly worse condition of the net. There was evidence for a linear trend in infection per category increase in deterioration of nets. In Equatorial Guinea IRS offered protection to those in sprayed and unsprayed houses alike when neighbourhood spray coverage was high (≥80%) compared to those living in areas of low IRS coverage (<20%), regardless of whether the house they lived in was sprayed or not (adjusted OR = 0.54, 95% CI 0.33-0.89). ITNs provided only personal protection, offering no protection to non users. Although similar effects were seen in Malawi, the evidence was much weaker than in Equatorial Guinea. CONCLUSIONS: Universal coverage strategies should consider policies for repair and replacement of holed nets and promote the care of nets by their owners. IRS programs should ensure high spray coverage since inadequate coverage gives little or no protection at all.

Does the perception of moving eyes trigger reflexive visual orienting in autism?

Does movement of the eyes in one or another direction function as an automatic attentional cue to a location of interest? Two experiments explored the directional movement of the eyes in a full face for speed of detection of an aftercoming location target in young people with autism and in control participants. Our aim was to investigate whether a low-level perceptual impairment underlies the delay in gaze following characteristic of autism. The participants' task was to detect a target appearing on the left or right of the screen either 100 ms or 800 ms after a face cue appeared with eyes averting to the left or right. Despite instructions to ignore eye-movement in the face cue, people with autism and control adolescents were quicker to detect targets that had been preceded by an eye movement cue congruent with target location compared with targets preceded by an incongruent eye movement cue. The attention shifts are thought to be reflexive because the cue was to be ignored, and because the effect was found even when cue-target duration was short (100 ms). Because (experiment two) the effect persisted even when the face was inverted, it would seem that the direction of movement of eyes can provide a powerful (involuntary) cue to a location.

Photoaptamer arrays applied to multiplexed proteomic analysis.

Multiplexed photoaptamer-based arrays that allow for the simultaneous measurement of multiple proteins of interest in serum samples are described. Since photoaptamers covalently bind to their target analytes before fluorescent signal detection, the arrays can be vigorously washed to remove background proteins, providing the potential for superior signal-to-noise ratios and lower limits of quantification in biological matrices. Data are presented here for a 17-plex photoaptamer array exhibiting limits of detection below 10 fM for several analytes including interleukin-16, vascular endothelial growth factor, and endostatin and able to measure proteins in 10% serum samples. The assays are simple, scalable, and reproducible. Affinity of the capture reagent is shown to be directly correlated to the limit of detection for the analyte on the array.