Division and subtraction by distinct cortical inhibitory networks in vivo

Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship

Summative behaviour change evaluation of up-to-date metered energy feedback in European public buildings

Energy consumption practices and behaviour are increasingly an important focus of attention, for energy efficiency measures. Such is the demand caused by behaviour at the level of the individual, it may cancel out the benefits of engineering solutions, such as more energy efficient appliances (Adua, 2010). This paper focuses on an evaluation of the SMARTSPACES project and its effect on energy-related behaviour change. The project provided two services: an energy management service (EMS) and an energy decision support service (EDSS). These services were implemented in over 450 public buildings across 11 European cities in 8 European countries (Serbia, France, Germany, Italy, The Netherlands, Spain, Turkey and United Kingdom). Building professionals (energy managers) primarily used the EMS and building staff used the EDSS. These services intended to inform, support and enable target audiences to use up-to-date metered feedback to reduce energy use in public buildings. The theory of change that underpins the evaluation framework is based in the Elaboration Likelihood Model which aims to understand how communication can influence attitudes and the Theory of Planned Behaviour that examines which attitudes are more likely to predict intentions and behaviours (Wilson, 2014). The paper presents results of ex-ante and ex-post surveys to building staff about their levels of awareness, attitudes, perceived control behaviour and intentions in three selected cities: Bristol, Leicester and Venlo. Outcomes varied across the examined cities depending upon the type of information presented, the level of engagement of users with the energy saving campaigns and the amount of previous energy management work undertaken by buildings’ facilities and energy management professionals

Brain activity and mental workload associated with artistic practice

We present the first stage of our on-going artist-driven BCI collaboration, where we equipped an artist with the brain scanning technique functional Near Infrared Spectroscopy (fNIRS) in order to record mental workload levels during her creative practice. The artists are interested in exposing the hidden cognitive processes involved in their creative practice, in order to reuse or integrate the data into their performances. The researchers are interested in collecting unstructured ‘in the wild’ fNIRS data, and to see how the artists interpret the data retrospectively. We highlight some interesting early examples from the data and describe our on-going plans. We will have completed a second data collection before the workshop

The Ursinus Weekly, October 30, 1961

Loyalty kick-off dinner features famous co-eds • Ursinus College treats Homecoming visitors to decorations, dinners, sports, and a dance: Haverford foe for Homecoming tilt; Campus readied • Six fraternity queens grace Homecoming scene • Work abroad plan offered by ASIS • Pfahler film festival shows Henry V, LaStrada • Placenta subject for Dr. Rathmell in pre-med talk • Senator Smith sees moral force as Khrushchev\u27s chief enemy • A-Phi-O welcomes thirteen pledges • Princeton\u27s Homrighausen visits here tomorrow • Dr. Parsons publishes Norris journal excerpt • Editorial: Censorship here • U.S. government offers junior Summer work • Social Security interview Friday in U.C. Library • Ursinus in the past • U.C. man is drag champ • The Late George Apley Curtain Club Fall choice • MSGA imposes fines for firebox tampering • Ursinus booters beat Muhlenberg, 2-1; Lose to Swarthmore Wenesday, 4-1 • Field hockey girls beat Stroudsburg • Leber-South unbeaten, unscored upon; Leads touch football teams • Wagner wrecks Bear hopes for a \u2761 winning campaign • Sophomore Scholl mainstay at end; Solid defensively, slick offensively • Dean\u27s listhttps://digitalcommons.ursinus.edu/weekly/1302/thumbnail.jp

Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12

The synaptonemal complex (SC) is a supramolecular protein scaffold that mediates chromosome synapsis and facilitates crossing over during meiosis. In mammals, SC proteins are generally assumed to have no other function. Here, we show that SC protein TEX12 also localises to centrosomes during meiosis independently of chromosome synapsis. In somatic cells, ectopically expressed TEX12 similarly localises to centrosomes, where it is associated with centrosome amplification, a pathology correlated with cancer development. Indeed, TEX12 is identified as a cancer-testis antigen and proliferation of some cancer cells is TEX12-dependent. Moreover, somatic expression of TEX12 is aberrantly activated via retinoic acid signalling, which is commonly disregulated in cancer. Structure-function analysis reveals that phosphorylation of TEX12 on tyrosine 48 is important for centrosome amplification but not for recruitment of TEX12 to centrosomes. We conclude that TEX12 normally localises to meiotic centrosomes, but its misexpression in somatic cells can contribute to pathological amplification and dysfunction of centrosomes in cancers

Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences

BACKGROUND: Patients’ treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients’ treatment preferences and identified key strategies to improve informed decision-making and trial recruitment. METHODS: Audio-recordings of 103 RCT recruitment appointments with 96 participants in three UK multicenter pragmatic RCTs were analyzed using content and thematic analysis. Recruiters’ responses to expressed treatment preferences were assessed in one RCT (ProtecT - Prostate testing for cancer and Treatment) in which training on exploring preferences had been given, and compared with two other RCTs where this specific training had not been given. RESULTS: Recruiters elicited treatment preferences similarly in all RCTs but responses to expressed preferences differed substantially. In the ProtecT RCT, patients’ preferences were not accepted at face value but were explored and discussed at length in three key ways: eliciting and acknowledging the preference rationale, balancing treatment views, and emphasizing the need to keep an open mind and consider all treatments. By exploring preferences, recruiters enabled participants to become clearer about whether their views were robust enough to be sustained or were sufficiently weak that participation in the RCT became possible. Conversely, in the other RCTs, treatment preferences were often readily accepted without further discussion or understanding the reasoning behind them, suggesting that patients were not given the opportunity to fully consider all treatments and trial participation. CONCLUSIONS: Recruiters can be trained to elicit and address patients’ treatment preferences, enabling those who may not have considered trial participation to do so. Without specific guidance, some RCT recruiters are likely to accept initial preferences at face value, missing opportunities to promote more informed decision-making. Training interventions for recruiters that incorporate key strategies to manage treatment preferences, as in the ProtecT study, are required to facilitate recruitment and informed consent. TRIAL REGISTRATION: ProtecT RCT: Current Controlled Trials ISRCTN20141297. The other two trials are registered but have asked to be anonymized

Optimising recruitment and informed consent in randomised controlled trials:the development and implementation of the QuinteT Recruitment Intervention (QRI)

BACKGROUND: Pragmatic randomised controlled trials (RCTs) are considered essential to determine effective interventions for routine clinical practice, but many fail to recruit participants efficiently, and some really important RCTs are not undertaken because recruitment is thought to be too difficult. The ‘QuinteT Recruitment Intervention’ (QRI) aims to facilitate informed decision making by patients about RCT participation and to increase recruitment. This paper presents the development and implementation of the QRI. METHODS: The QRI developed iteratively as a complex intervention. It emerged from the National Institute for Health Research (NIHR) ProtecT trial and has been developed further in 13 RCTs. The final version of the QRI uses a combination of standard and innovative qualitative research methods with some simple quantification to understand recruitment and identify sources of difficulties. RESULTS: The QRI has two major phases: understanding recruitment as it happens and then developing a plan of action to address identified difficulties and optimise informed consent in collaboration with the RCT chief investigator (CI) and the Clinical Trials Unit (CTU). The plan of action usually includes RCT-specific, as well as generic, aspects. The QRI can be used in two ways: it can be integrated into the feasibility/pilot or main phase of an RCT to prevent difficulties developing and optimise recruitment from the start, or it can be applied to an ongoing RCT experiencing recruitment shortfalls, with a view to rapidly improving recruitment and informed consent or gathering evidence to justify RCT closure. CONCLUSIONS: The QRI provides a flexible way of understanding recruitment difficulties and producing a plan to address them while ensuring engaged and well-informed decision making by patients. It can facilitate recruitment to the most controversial and important RCTs. QRIs are likely to be of interest to the CIs and CTUs developing proposals for ‘difficult’ RCTs or for RCTs with lower than expected recruitment and to the funding bodies wishing to promote efficient recruitment in pragmatic RCTs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1391-4) contains supplementary material, which is available to authorized users

Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand

Acknowledgments Supported by an unrestricted departmental grant from Research to Prevent Blindness (New York, NY), NEI K08EY023998 (KLP), P30-EY001730 (RVG; Bethesda, MD), by a grant from Elasmogen Limited (RVG), and with support from the Mark J. Daily, MD Research Fund (RVG, KLP).Peer reviewedPublisher PD