Urine Calcium But Not Plasma Calcium or Urine Hydroxyproline Is Increased by a Systemic Acidosis in the Dairy Cow

Eight non-lactating, pregnant Holstein-Friesian cows were allocated to two treatments and individually offered diets differing in dietary cation-anion difference. Decreasing the dietary cation-anion difference reduced the urine pH within hours of anionic salt supplementation. Plasma calcium concentration was unaffected by dietary cation-anion difference but urine calcium concentration was significantly increased within 10 days of including anionic salts in the diet. Faecal calcium concentration was significantly reduced, indicating increased calcium absorption. Dietary calcium concentration or dietary cationanion difference did not significantly affect urinary hydroxyproline

Dry Matter Intake of Periparturient Cows on a Fresh Pasture/Pasture-Hay Diet

Reports of the depression in dry matter intake in the periparturient period have been inconsistent and little dry matter intake data is available for an all-forage diet prior to calving. Data to examine intake depression prior to calving was obtained from two experiments. In experiment 1, sixteen non-lactating, periparturient cows ate 1.3% of pre-calving body weight of grass-hay and freshly cut grass for two weeks pre-calving (restricted). Experiment 2 comprised thiry-six cows that ate 1.6% of pre-calving body weight of grass-hay and freshly cut grass for the final two weeks of pregnancy (ad libitum). Individual dry matter intakes were recorded for 14 days pre-calving. Intake pre-calving was not depressed, irrespective of feeding level, until two days pre-calving. This suggests that when an all-forage diet is fed pre-calving, increasing the energy density of the diet to compensate for a depression in dry matter intake may not be necessary

Identification of an allosteric binding site on the human glycine transporter, GlyT2, for bioactive lipid analgesics

© Mostyn et al. The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters

Improving ranking for systematic reviews using query adaptation

Identifying relevant studies for inclusion in systematic reviews requires significant effort from human experts who manually screen large numbers of studies. The problem is made more difficult by the growing volume of medical literature and Information Retrieval techniques have proved to be useful to reduce workload. Reviewers are often interested in particular types of evidence such as Diagnostic Test Accuracy studies. This paper explores the use of query adaption to identify particular types of evidence and thereby reduce the workload placed on reviewers. A simple retrieval system that ranks studies using TF.IDF weighted cosine similarity was implemented. The Log-Likelihood, ChiSquared and Odds-Ratio lexical statistics and relevance feedback were used to generate sets of terms that indicate evidence relevant to Diagnostic Test Accuracy reviews. Experiments using a set of 80 systematic reviews from the CLEF2017 and CLEF2018 eHealth tasks demonstrate that the approach improves retrieval performance

Velocity Amplitudes in Global Convection Simulations: The Role of the Prandtl Number and Near-Surface Driving

Several lines of evidence suggest that the velocity amplitude in global simulations of solar convection, U, may be systematically over-estimated. Motivated by these recent results, we explore the factors that determine U and we consider how these might scale to solar parameter regimes. To this end, we decrease the thermal diffusivity $\kappa$ along two paths in parameter space. If the kinematic viscosity $\nu$ is decreased proportionally with $\kappa$ (fixing the Prandtl number $P_r = \nu/\kappa$), we find that U increases but asymptotes toward a constant value, as found by Featherstone & Hindman (2016). However, if $\nu$ is held fixed while decreasing $\kappa$ (increasing $P_r$), we find that U systematically decreases. We attribute this to an enhancement of the thermal content of downflow plumes, which allows them to carry the solar luminosity with slower flow speeds. We contrast this with the case of Rayleigh-Benard convection which is not subject to this luminosity constraint. This dramatic difference in behavior for the two paths in parameter space (fixed $P_r$ or fixed $\nu$) persists whether the heat transport by unresolved, near-surface convection is modeled as a thermal conduction or as a fixed flux. The results suggest that if solar convection can operate in a high-$P_r$ regime, then this might effectively limit the velocity amplitude. Small-scale magnetism is a possible source of enhanced viscosity that may serve to achieve this high-$P_r$ regime.Comment: 34 Pages, 8 Figures, submitted to a special issue of "Advances in Space Research" on "Solar Dynamo Frontiers

A genome-wide association study to identify genetic markers associated with endometrial cancer grade

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Understanding communication pathways to foster community engagement for health improvement in North West Pakistan

Background: This paper describes the community engagement process undertaken to ascertain the focus, development and implementation of an intervention to improve iodised salt consumption in rural communities in North West Pakistan. The Jirga is a traditional informal structure, which gathers men respected within their community and acts in a governing and decision making capacity in the Pukhtoon culture. The Jirga system had a dual purpose for the study; to access men from the community to discuss the importance of iodised salt, and as an engagement process for the intervention. Methods: A number of qualitative data collection activities were undertaken, with Jirga members and their wives, male and female outreach workers and two groups of women, under and over forty years old. The aim of these were to highlight the communication channels and levers of influence on health behaviour, which were multiple and complex and all needed to be taken into consideration in order to ensure successful and locally sensitive community engagement. Results: Communication channels are described within local families and the communities around them. The key influential role of the Jirga is highlighted as linked both to the standing of its members and the community cohesion ethos that it embodies. Engaging Jirga members in discussions about iodised salt was key in designing an intervention that would activate the most influential levers to decision making in the community. Gendered decision making-processes within the household have been highlighted as restricting women’s autonomy. Whilst in one respect our data confirm this, a more complex hierarchy of decisional power has been highlighted, whereby the concept of ‘wisdom’, an amalgamation of age, experience and education, presents important possibilities. Community members with the least autonomy are the youngest uneducated females, who rely on a web of socially and culturally determined ways to influence decision-making. Conclusions: The major lines of communication and influence in the local community described are placed within the wider literature on community engagement in health improvement. The process of maximisation of local cultural knowledge as part of a community engagement effort is one that has application well beyond the particular setting of this study

Systematic Reviews in Educational Research: Methodology, Perspectives and Application

This chapter explores the processes of reviewing literature as a research method. The logic of the family of research approaches called systematic review is analysed and the variation in techniques used in the different approaches explored using examples from existing reviews. The key distinctions between aggregative and configurative approaches are illustrated and the chapter signposts further reading on key issues in the systematic review process

The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

© 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible ‘knockdown’ mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3–4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin−5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder