TILT: Time-Lapse Imaging Trial-a pragmatic, multi-centre, three-arm randomised controlled trial to assess the clinical effectiveness and safety of time-lapse imaging in in vitro fertilisation treatment

Background: Subfertility is a common problem for which in vitro fertilisation (IVF) treatment is commonly recommended. Success rates following IVF are suboptimal and have remained static over the last few years. This imposes a considerable financial burden on overstretched healthcare resources. Time-lapse imaging (TLI) of developing embryos in IVF treatment is hypothesised to improve the success rates of treatment. This may be either by providing undisturbed culture conditions or by improving the predictive accuracy for optimal embryo selection from a cohort of available embryos. However, the current best evidence for its effectiveness is inconclusive. Methods: The time-lapse imaging trial is a pragmatic, multi-centre, three-arm parallel-group randomised controlled trial using re-randomisation. The primary objective of the trial is to determine if the use of TLI or undisturbed culture in IVF treatment results in a higher live birth rate when compared to current standard methods of embryo incubation and assessment. Secondary outcomes include measures of clinical efficacy and safety. The trial will randomise 1575 participants to detect an increase in live birth from 26.5 to 35.25%. Discussion: In the absence of high-quality evidence, there is no current national guidance, recommendation or policy for the use of TLI. The use of TLI is not consistently incorporated into standard IVF care. A large, pragmatic, multi-centre, trial will provide much needed definitive evidence regarding the effectiveness of TLI. If proven to be effective, its incorporation into standard care would translate into significant clinical and economic benefits. If not, it would allow allocation of resources to more effective interventions.Barts CharityChinese University of Hong KongHealth and Medical Research Fund, Food and Health Bureau, The Government of Hong Kong SAR 0718056

Towards high-speed optical quantum memories

Quantum memories, capable of controllably storing and releasing a photon, are a crucial component for quantum computers and quantum communications. So far, quantum memories have operated with bandwidths that limit data rates to MHz. Here we report the coherent storage and retrieval of sub-nanosecond low intensity light pulses with spectral bandwidths exceeding 1 GHz in cesium vapor. The novel memory interaction takes place via a far off-resonant two-photon transition in which the memory bandwidth is dynamically generated by a strong control field. This allows for an increase in data rates by a factor of almost 1000 compared to existing quantum memories. The memory works with a total efficiency of 15% and its coherence is demonstrated by directly interfering the stored and retrieved pulses. Coherence times in hot atomic vapors are on the order of microsecond - the expected storage time limit for this memory.Comment: 13 pages, 5 figure

Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

Association between average daily gain, faecal dry matter content and concentration of Lawsonia intracellularis in faeces

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to investigate the association between average daily gain and the number of <it>Lawsonia intracellularis</it> bacteria in faeces of growing pigs with different levels of diarrhoea.</p> <p>Methods</p> <p>A longitudinal field study (<it>n</it> = 150 pigs) was performed in a Danish herd from day 29 to 47 post weaning. Every third day all pigs were weighed, subjected to a clinical examination and faecal samples were obtained. Faecal samples were subjected to dry matter determination and absolute quantification by PCR for <it>L. intracellularis</it> and porcine circovirus type 2 (PCV2). Association between average daily gain, faecal dry matter content, numbers of <it>L. intracellularis</it> bacteria and PCV2 genome copies in faeces was investigated in a multilevel mixed-effects linear model.</p> <p>Results</p> <p>Increasing numbers of <it>L. intracellularis</it> log₁₀ bacteria/g faeces were significantly associated with decreasing average daily gain (<it>P</it> < 0.001). The association was decreasing with increasing faecal dry matter content (<it>P</it> < 0.01). The number of PCV2 log₁₀ copies/g faeces was not significantly associated with average daily gain of the pigs (<it>P</it> > 0.5).</p> <p>Conclusion</p> <p>The results suggest a potential application of a PCR quantifying <it>L. intracellularis</it> in growing pigs. Faecal dry matter content must be taken into consideration in interpretation of such test results.</p

Statistical methods in language processing

The term statistical methods here refers to a methodology that has been dominant in computational linguistics since about 1990. It is characterized by the use of stochastic models, substantial data sets, machine learning, and rigorous experimental evaluation. The shift to statistical methods in computational linguistics parallels a movement in artificial intelligence more broadly. Statistical methods have so thoroughly permeated computational linguistics that almost all work in the field draws on them in some way. There has, however, been little penetration of the methods into general linguistics. The methods themselves are largely borrowed from machine learning and information theory. We limit attention to that which has direct applicability to language processing, though the methods are quite general and have many nonlinguistic applications. Not every use of statistics in language processing falls under statistical methods as we use the term. Standard hypothesis testing and experimental design, for example, are not covered in this article. WIREs Cogni Sci 2011 2 315–322 DOI: 10.1002/wcs.111 For further resources related to this article, please visit the WIREs websitePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83468/1/111_ftp.pd

Considering the role of cognitive control in expert performance

© 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention