Mouse frontal cortex mediates additive multisensory decisions

The brain can combine auditory and visual information to localize objects. However, the cortical substrates underlying audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. We trained mice in an audiovisual localization task. Inactivating frontal cortex impaired responses to either sensory modality, while inactivating visual or parietal cortex affected only visual stimuli. Recordings from >14,000 neurons indicated that after task learning, activity in the anterior part of frontal area MOs (secondary motor cortex) additively encodes visual and auditory signals, consistent with the mice's behavioral strategy. An accumulator model applied to these sensory representations reproduced the observed choices and reaction times. These results suggest that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator

Micro-volume couette flow sample orientation for absorbance and fluorescence linear dichroism

Linear dichroism (LD) can be used to study the alignment of absorbing chromophores within long molecules. In particular, Couette flow LD has been used to good effect in probing ligand binding to DNA and to fibrous proteins. This technique has been previously limited by large sample requirements. Here we report the design and application of a new micro-volume Couette flow cell that significantly enhances the potential applications of flow LD spectroscopy by reducing the sample requirements for flow linear dichroism to 25 μL (with concentrations such that the absorbance maximum of the sample in a 1-cm pathlength cuvette is not, vert, similar1). The micro-volume Couette cell has also enabled the measurement of fluorescence-detected Couette flow linear dichroism. This new technique enables the orientation of fluorescent ligands to be probed even when their electronic transitions overlap with those of the macromolecule and conversely. The potential of flow-oriented fluorescence dichroism and application of the micro-volume Couette LD cell are illustrated by the collection of data for DNA with minor groove and intercalating ligands: DAPI, Hoechst, and ethidium bromide. As with conventional fluorescence, improved sensitivity compared with absorbance LD is to be expected after instrumentation optimization

High-yield methods for accurate two-alternative visual psychophysics in head-fixed mice

Research in neuroscience increasingly relies on the mouse, a mammalian species that affords unparalleled genetic tractability and brain atlases. Here, we introduce high-yield methods for probing mouse visual decisions. Mice are head-fixed, facilitating repeatable visual stimulation, eye tracking, and brain access. They turn a steering wheel to make two alternative choices, forced or unforced. Learning is rapid thanks to intuitive coupling of stimuli to wheel position. The mouse decisions deliver high-quality psychometric curves for detection and discrimination and conform to the predictions of a simple probabilistic observer model. The task is readily paired with two-photon imaging of cortical activity. Optogenetic inactivation reveals that the task requires mice to use their visual cortex. Mice are motivated to perform the task by fluid reward or optogenetic stimulation of dopamine neurons. This stimulation elicits a larger number of trials and faster learning. These methods provide a platform to accurately probe mouse vision and its neural basis

Developing reading-writing connections; the impact of explicit instruction of literary devices on the quality of children's narrative writing

The purpose of this collaborative schools-university study was to investigate how the explicit instruction of literary devices during designated literacy sessions could improve the quality of children's narrative writing. A guiding question for the study was: Can children's writing can be enhanced by teachers drawing attention to the literary devices used by professional writers or “mentor authors”? The study was conducted with 18 teachers, working as research partners in nine elementary schools over one school year. The research group explored ways of developing children as reflective authors, able to draft and redraft writing in response to peer and teacher feedback. Daily literacy sessions were complemented by weekly writing workshops where students engaged in authorial activity and experienced writers' perspectives and readers' demands (Harwayne, 1992; May, 2004). Methods for data collection included video recording of peer-peer and teacher-led group discussions and audio recording of teacher-child conferences. Samples of children's narrative writing were collected and a comparison was made between the quality of their independent writing at the beginning and end of the research period. The research group documented the importance of peer-peer and teacher-student discourse in the development of children's metalanguage and awareness of audience. The study suggests that reading, discussing, and evaluating mentor texts can have a positive impact on the quality of children's independent writing

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients

Considerations and best practices in animal science 16S ribosomal RNA gene sequencing microbiome studies

Microbiome studies in animal science using 16S rRNA gene sequencing have become increasingly common in recent years as sequencing costs continue to fall and bioinformatic tools become more powerful and user-friendly. The combination of molecular biology, microbiology, microbial ecology, computer science, and bioinformatics—in addition to the traditional considerations when conducting an animal science study—makes microbiome studies sometimes intimidating due to the intersection of different fields. The objective of this review is to serve as a jumping-off point for those animal scientists less familiar with 16S rRNA gene sequencing and analyses and to bring up common issues and concerns that arise when planning an animal microbiome study from design through analysis. This review includes an overview of 16S rRNA gene sequencing, its advantages, and its limitations; experimental design considerations such as study design, sample size, sample pooling, and sample locations; wet lab considerations such as field handing, microbial cell lysis, low biomass samples, library preparation, and sequencing controls; and computational considerations such as identification of contamination, accounting for uneven sequencing depth, constructing diversity metrics, assigning taxonomy, differential abundance testing, and, finally, data availability. In addition to general considerations, we highlight some special considerations by species and sample type

Perceived usefulness of a distributed community-based syndromic surveillance system: a pilot qualitative evaluation study

<p>Abstract</p> <p>Background</p> <p>We conducted a pilot utility evaluation and information needs assessment of the Distribute Project at the 2010 Washington State Public Health Association (WSPHA) Joint Conference. Distribute is a distributed community-based syndromic surveillance system and network for detection of influenza-like illness (ILI). Using qualitative methods, we assessed the perceived usefulness of the Distribute system and explored areas for improvement. Nine state and local public health professionals participated in a focus group (<it>n = 6</it>) and in semi-structured interviews (<it>n = 3</it>). Field notes were taken, summarized and analyzed.</p> <p>Findings</p> <p>Several emergent themes that contribute to the perceived usefulness of system data and the Distribute system were identified: 1) <it>Standardization: </it>a common ILI syndrome definition; 2) <it>Regional Comparability: </it>views that support county-by-county comparisons of syndromic surveillance data; 3) <it>Completeness: </it>complete data for all expected data at a given time; <it>4) Coverage: </it>data coverage of all jurisdictions in WA state; 5) <it>Context: </it>metadata incorporated into the views to provide context for graphed data; 6) <it>Trusted Data</it>: verification that information is valid and timely; and 7) <it>Customization: </it>the ability to customize views as necessary. As a result of the focus group, a new county level health jurisdiction expressed interest in contributing data to the Distribute system.</p> <p>Conclusion</p> <p>The resulting themes from this study can be used to guide future information design efforts for the Distribute system and other syndromic surveillance systems. In addition, this study demonstrates the benefits of conducting a low cost, qualitative evaluation at a professional conference.</p

The role of contracting strategies in social value implementation

There has been an increasing demand for social value (SV) implementation to assume a cardinal position in the infrastructure delivery efforts of infrastructure client organisations (ICOs). However, whereas successful implementation has been recorded in some projects, monumental failures have also been recorded in others. This variance in implementation performance is a cause for concern. The mode of governance applied in an infrastructure delivery endeavour has been identified as capable of influencing the implementation of SV. This observation makes imperative an investigation into the role of contracting strategies – an integral part of governance modes – adopted by ICOs on SV implementation performance. This is the aim of this study. Using a case study approach, three infrastructure projects which used different contracting strategies were selected from two different countries, the UK and Nigeria. Semistructured interviews were conducted with ICO representatives on these projects and subsequently analysed using qualitative content analysis. Findings confirmed that the kind of contract adopted by ICOs influenced their ability to drive the successful implementation of desirable SV objectives through their supply chain. It is therefore recommended that ICOs ensure that the selected contracting strategies are capable of ensuring successful implementation of the desired objectives