Tensor clustering with algebraic constraints gives interpretable groups of crosstalk mechanisms in breast cancer.

We introduce a tensor-based clustering method to extract sparse, low-dimensional structure from high-dimensional, multi-indexed datasets. This framework is designed to enable detection of clusters of data in the presence of structural requirements which we encode as algebraic constraints in a linear program. Our clustering method is general and can be tailored to a variety of applications in science and industry. We illustrate our method on a collection of experiments measuring the response of genetically diverse breast cancer cell lines to an array of ligands. Each experiment consists of a cell line-ligand combination, and contains time-course measurements of the early signalling kinases MAPK and AKT at two different ligand dose levels. By imposing appropriate structural constraints and respecting the multi-indexed structure of the data, the analysis of clusters can be optimized for biological interpretation and therapeutic understanding. We then perform a systematic, large-scale exploration of mechanistic models of MAPK-AKT crosstalk for each cluster. This analysis allows us to quantify the heterogeneity of breast cancer cell subtypes, and leads to hypotheses about the signalling mechanisms that mediate the response of the cell lines to ligands.

Gram Determinants of Real Binary Tensors.

A binary tensor consists of 2 n entries arranged into hypercube format 2 × 2 × â‹¯ × 2. There are n ways to flatten such a tensor into a matrix of size 2 × 2 n-1. For each flattening, M, we take the determinant of its Gram matrix, det(MMT ). We consider the map that sends a tensor to its n-tuple of Gram determinants. We propose a semi-algebraic characterization of the image of this map. This offers an answer to a question raised by Hackbusch and Uschmajew concerning the higher-order singular values of tensors.

Does Antibiotic Resistance Evolve in Hospitals?

Nosocomial outbreaks of bacteria are well documented. Based on these incidents, and the heavy usage of antibiotics in hospitals, it has been assumed that antibiotic resistance evolves in hospital environments. To test this assumption, we studied resistance phenotypes of bacteria collected from patient isolates at a community hospital over a 2.5-year period. A graphical model analysis shows no association between resistance and patient information other than time of arrival. This allows us to focus on time-course data. We introduce a hospital transmission model, based on negative binomial delay. Our main contribution is a statistical hypothesis test called the Nosocomial Evolution of Resistance Detector (NERD). It calculates the significance of resistance trends occurring in a hospital. It can inform hospital staff about the effects of various practices and interventions, can help detect clonal outbreaks, and is available as an R package. We applied the NERD method to each of the 16 antibiotics in the study via 16 hypothesis tests. For 13 of the antibiotics, we found that the hospital environment had no significant effect on the evolution of resistance; the hospital is merely a piece of the larger picture. The p-values obtained for the other three antibiotics (cefepime, ceftazidime, and gentamicin) indicate that particular care should be taken in hospital practices with these antibiotics. One of the three, ceftazidime, was significant after accounting for multiple hypotheses, indicating a trend of decreased resistance for this drug.

Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents.

Sex differences have been found amongst toddlers and young children with autism spectrum disorder (ASD). We investigated the presence and stability of these ASD sex differences throughout childhood and adolescence. Participants (N = 325, 52 females; aged 3-18 years) consecutively received an ASD diagnosis at a clinic for assessing high-functioning ASD (mean verbal IQ = 92.6). There were no IQ sex differences. By parent report and direct observation, females had less repetitive stereotyped behaviour (RSB), with male-equivalent levels of social and communication impairment. Teachers reported males with ASD as having greater externalising and social problems than females. The female phenotype we describe was stable across our sample's age range. Their milder RSBs and less severe difficulties at school may lead to under-recognition of ASD in females.

Can autistic children read the mind of an animated triangle?

Are children with an autism spectrum disorder (ASD), but normal-range intelligence, impaired on theory of mind skills measured by responses to abstract animations in the form of a computerized cartoon? Fifty-six cases and closely matched comparisons were tested. We rated verbal responses according to the length of their descriptions, their appropriateness and the children's use of 'mentalizing' terms. Children with ASD used 'mentalizing' language to describe the animations as well as comparisons, although the content of their descriptions was significantly less appropriate. Performance on this task was not well correlated with standardized measures of parent-reported behaviour or the child's interactions with an observer. The implications of our results are discussed in relation to previous studies that have used this methodology.

Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is sufficiently important as to warrant co-administration of misoprostol or proton pump inhibitors or a switch to selective cyclooxygenase (COX)-2 inhibitors. However, the serious ulcer outcome studies suggested that 40% of the clinically significant gastrointestinal bleeding originated more distally, presumably from NSAID enteropathy. We used capsule enteroscopy to study small-bowel damage in patients on long-term NSAIDs and COX-2-selective agents. METHODS: Sixty healthy volunteers acted as controls. One hundred twenty and 40 patients on long-term NSAIDs and COX-2 selective agents, respectively, underwent a capsule enteroscopy study. Small-bowel damage was categorized and quantitated. RESULTS: Sixty-two percent of patients on conventional NSAIDs were abnormal, which differed significantly (P < .001) from controls. The main pathology related to reddened folds (13%), denuded areas (39%), and mucosal breaks (29%). Two percent had diaphragm-like strictures and 3% had bleeding without an identifiable lesion. The damage, seen in 50% of patients on selective COX-2 inhibitors (reddened folds, 8%; denuded areas, 18%; and mucosal breaks, 22%), did not differ significantly (P > .5) from that seen with NSAIDs. CONCLUSIONS: Long-term NSAIDs and COX-2-selective agents cause comparable small-bowel damage. This suggests an important role for COX-2 in the maintenance of small-bowel integrity. The results have implications for strategies that aim to minimize the gastrointestinal damage in patients requiring anti-inflammatory analgesics.

Eye tracking and fear recognition deficits in Turner syndrome.

Turner syndrome (TS) is a chromosomal disorder of X-monosomy in females. A minority have impaired social responsiveness, poor discrimination of facial emotions (especially fear), and abnormal amygdala-cortical connectivity. We tested the hypothesis that abnormal gaze fixation, especially with the eye region of faces, would be associated with these features, in a similar pattern to that seen in subjects with autism. Furthermore, since these features tend to be more striking in TS women whose X chromosome is maternal in origin, we also predicted that there may be a difference within the Turner's group according to parental origin of the single X. Adults with 45,X karyotype and age and IQ matched 46,XX women were recruited and tested. Facial fear recognition was significantly worse in 45,X females than controls, but there were no group differences according to parental origin of their single X chromosome. Subsequently, we tested 45,X and 46,XX women using a remote eye-tracking device, as they viewed photographs of emotional human faces. Striking differences in scanpaths were found between the TS and controls, and within the TS group, but not according to parental origin of the X chromosome. These findings provide novel evidence for abnormal face processing in some women with TS, and indicate a potential neural mechanism underlying the difficulties in some key aspects of social cognition.