Neuropharmacological targets for drug action in vestibular sensory pathways

The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e., glutamate (Glu) and acetylcholine (ACh)] or alter their patterns of release. This review summarizes various efforts to identify drug targets including neurotransmitter and neuromodulator receptors in the vestibular sensory pathways. Identifying these receptor targets provides a strategic basis to use specific pharmacological tools to modify receptor function in the treatment and management of debilitating balance disorders. A review of the literature reveals that most investigations of the neuropharmacology of peripheral vestibular function have been performed using in vitro or ex vivo animal preparations rather than studying drug action on the normal intact vestibular system in situ. Such noninvasive approaches could aid the development of more accurate and effective intervention strategies for the treatment of dizziness and vertigo. The current review explores the major neuropharmacological targets for drug action in the vestibular system

The Price Impact of Order Book Events

We study the price impact of order book events - limit orders, market orders and cancelations - using the NYSE TAQ data for 50 U.S. stocks. We show that, over short time intervals, price changes are mainly driven by the order flow imbalance, defined as the imbalance between supply and demand at the best bid and ask prices. Our study reveals a linear relation between order flow imbalance and price changes, with a slope inversely proportional to the market depth. These results are shown to be robust to seasonality effects, and stable across time scales and across stocks. We argue that this linear price impact model, together with a scaling argument, implies the empirically observed "square-root" relation between price changes and trading volume. However, the relation between price changes and trade volume is found to be noisy and less robust than the one based on order flow imbalance

Evaluation of HIV counseling and testing in ANC settings and adherence to short course antiretroviral prophylaxis for PMTCT in Francistown, Botswana

Worldwide, it is estimated that two million children are infected with HIV (USAID 2005). The vast majority of these infections are the result of mother-to-child transmission (MTCT) of the virus during pregnancy, labor, or breastfeeding. However, there are effective methods for prevention of mother-to-child transmission (PMTCT). Botswana is one of the first countries in the developing world with a national PMTCT program that uses an efficacious and complex regimen to reduce vertical transmission. At the time of this evaluation (August - December 2005), the standard of care for prevention of MTCT of HIV in Botswana included three-drug antiretroviral therapy for HIV-infected women with a CD4 count of 200 (300 mg AZT in the morning and 300 mg AZT in the evening); four weeks of AZT for their infants; single-dose maternal and infant nevirapine (NVP); and 12 months of free infant formula. Botswana's PMTCT program also provided routine HIV testing for all pregnant women during antenatal care (ANC) to identify HIV-positive women for prophylaxis or treatment. While programs often report the number of individuals beginning AZT and receiving nevirapine for PMTCT, effectiveness is dependent on the level of adherence of individuals to these regimens. To describe adherence of pregnant women to the current PMTCT regimen, the Horizons Program of the Population Council, in collaboration with the Centers for Disease Control and Prevention (CDC) and Premiere Personnel in Botswana, conducted an evaluation to describe HIV-related services provided to women during their pregnancies, document the content of post-test counseling sessions for HIV-positive pregnant women, whether HIV-positive women remembered what had been discussed, the extent of AZT adherence based on self-reports, and the operational successes and barriers to adherence to AZT for PMTCT

Smart Content Recognition from Images Using a Mixture of Convolutional Neural Networks

With rapid development of the Internet, web contents become huge. Most of the websites are publicly available, and anyone can access the contents from anywhere such as workplace, home and even schools. Nevertheless, not all the web contents are appropriate for all users, especially children. An example of these contents is pornography images which should be restricted to certain age group. Besides, these images are not safe for work (NSFW) in which employees should not be seen accessing such contents during work. Recently, convolutional neural networks have been successfully applied to many computer vision problems. Inspired by these successes, we propose a mixture of convolutional neural networks for adult content recognition. Unlike other works, our method is formulated on a weighted sum of multiple deep neural network models. The weights of each CNN models are expressed as a linear regression problem learned using Ordinary Least Squares (OLS). Experimental results demonstrate that the proposed model outperforms both single CNN model and the average sum of CNN models in adult content recognition.Comment: To be published in LNEE, Code: github.com/mundher/NSF

Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

Sustainable built asset management performance indicators and attributes : a UK social housing case study example

This paper aims to identify key performance indicators (KPI), and their corresponding attributes, required to successfully manage asset management sustainably in a built environment context. Improving the sustainability of existing housing stock is a major challenge facing the UK social housing sector. There is a lack of support to navigate the growing and often incongruent information relating to sustainable development and how to operationalise it. The problem is twofold; firstly, the current (single criterion) condition-based approach to maintenance planning constrains Asset Managers and does not fully address the social, environmental and economic aspects of sustainability. Secondly, the toolkits available for assessing the sustainability of housing are often generic and are time consuming and expensive to implement. This paper reports the findings of a participatory research project with a leading London based housing association, using a series of landlord and tenant workshops to derive a set of attributes associated with key performance indicators (KPIs) to fully reflect the local requirements of the landlord and their interpretation of the sustainability agenda. Five KPIs considered to be measurable, directly affected by maintenance work and independent of each other were identified by this landlord (comfort, running costs, adaptability, maintenance costs and community).The resulting outputs, in a policy context, will provide a clear route-map to social housing landlords of how to improve the sustainability of their housing stock with the additional benefits of addressing fuel poverty, carbon emissions targets whilst at the same time help create and maintain housing in which people want to live. The proposed approach is flexible enough to incorporate the individual requirements of landlords, be able to adapt to changes in government policy (local and central) in a timely, robust, transparent and inclusive format

Literacy-related professional development preferences of secondary teachers

A survey of 100 teachers in one Ontario school board examined their literacy-related professional development preferences. The majority preferred short durations of literacy-related professional development. A small number did not want any literacy-related professional development. The most preferred forms of professional development were shared practice, mentoring, observation of colleagues, and collaborative lesson development. Preferences for form and content of professional development varied between subject areas and course types. Un sondage a été réalisé auprès de 100 enseignants d’une commission scolaire ontarienne afin de déterminer leurs préférences en matière de perfectionnement professionnel lié à l’alphabétisme. La majorité des enseignants sondés préfèrent des cours de courte durée de perfectionnement professionnel lié à l’alphabétisme. Un petit nombre ne souhaite suivre aucun cours de perfectionnement professionnel lié à l’alphabétisme. Les formes préférées de perfectionnement professionnel sont les pratiques partagées, le mentorat, l’observation des collègues et le développement collaboratif de systèmes éducatifs. Les préférences en matière de forme et de contenu du perfectionnement professionnel varient fonction de la discipline et du genre de cours.

Type-Inference Based Short Cut Deforestation (nearly) without Inlining

Deforestation optimises a functional program by transforming it into another one that does not create certain intermediate data structures. In [ICFP'99] we presented a type-inference based deforestation algorithm which performs extensive inlining. However, across module boundaries only limited inlining is practically feasible. Furthermore, inlining is a non-trivial transformation which is therefore best implemented as a separate optimisation pass. To perform short cut deforestation (nearly) without inlining, Gill suggested to split definitions into workers and wrappers and inline only the small wrappers, which transfer the information needed for deforestation. We show that Gill's use of a function build limits deforestation and note that his reasons for using build do not apply to our approach. Hence we develop a more general worker/wrapper scheme without build. We give a type-inference based algorithm which splits definitions into workers and wrappers. Finally, we show that we can deforest more expressions with the worker/wrapper scheme than the algorithm with inlining

Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

Objective To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. Design Longitudinal, observational design. Setting Osteoarthritis Initiative cohort. Participants Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 Interventions Not applicable. Main Outcome Measures Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. Results Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by −.072 (95% confidence interval, −.121 to −.020). Conclusions Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective

The expected performance of stellar parametrization with Gaia spectrophotometry

Gaia will obtain astrometry and spectrophotometry for essentially all sources in the sky down to a broad band magnitude limit of G=20, an expected yield of 10^9 stars. Its main scientific objective is to reveal the formation and evolution of our Galaxy through chemo-dynamical analysis. In addition to inferring positions, parallaxes and proper motions from the astrometry, we must also infer the astrophysical parameters of the stars from the spectrophotometry, the BP/RP spectrum. Here we investigate the performance of three different algorithms (SVM, ILIUM, Aeneas) for estimating the effective temperature, line-of-sight interstellar extinction, metallicity and surface gravity of A-M stars over a wide range of these parameters and over the full magnitude range Gaia will observe (G=6-20mag). One of the algorithms, Aeneas, infers the posterior probability density function over all parameters, and can optionally take into account the parallax and the Hertzsprung-Russell diagram to improve the estimates. For all algorithms the accuracy of estimation depends on G and on the value of the parameters themselves, so a broad summary of performance is only approximate. For stars at G=15 with less than two magnitudes extinction, we expect to be able to estimate Teff to within 1%, logg to 0.1-0.2dex, and [Fe/H] (for FGKM stars) to 0.1-0.2dex, just using the BP/RP spectrum (mean absolute error statistics are quoted). Performance degrades at larger extinctions, but not always by a large amount. Extinction can be estimated to an accuracy of 0.05-0.2mag for stars across the full parameter range with a priori unknown extinction between 0 and 10mag. Performance degrades at fainter magnitudes, but even at G=19 we can estimate logg to better than 0.2dex for all spectral types, and [Fe/H] to within 0.35dex for FGKM stars, for extinctions below 1mag.Comment: MNRAS, in press. Minor corrections made in v