The effects of memantine on prepulse inhibition.

Reduced prepulse inhibition (PPI) of startle provides evidence of deficient sensorimotor gating in several disorders, including schizophrenia. The role of NMDA neurotransmission in the regulation of PPI is unclear, due to cross-species differences in the effects of NMDA antagonists on PPI. Recent reports suggest that drug effects on PPI differ in subgroups of normal humans that differ in the levels of baseline PPI or specific personality domains; here, we tested the effects of these variables on the sensitivity of PPI to the NMDA antagonist, memantine. PPI was measured in male Sprague-Dawley rats, after treatment with memantine (0, 10 or 20 mg/kg, s.c.). Baseline PPI was then measured in 37 healthy adult men. Next, subjects were tested twice, in a double-blind crossover design, comparing either (1) placebo vs 20 mg of the NMDA antagonist memantine (n=19) or (2) placebo vs 30 mg memantine (n=18). Tests included measures of acoustic startle amplitude, PPI, autonomic indices and subjective self-rating scales. Memantine had dose- and interval-dependent effects on PPI in rats. Compared with vehicle, 10 mg/kg increased short-interval (10-20 ms) PPI, and 20 mg/kg decreased long-interval (120 ms) PPI. In humans, memantine caused dose-dependent effects on psychological and somatic measures: 20 mg was associated with increased ratings of happiness, and 30 mg was associated with increased ratings of dizziness. PPI at the 120 ms prepulse interval was increased by 20 mg, but not 30 mg of memantine. Subgroups most sensitive to the PPI-enhancing effects of memantine were those with low baseline PPI, or with personality scale scores suggestive of high novelty seeking, high sensation seeking, or high disinhibition. NMDA blockade with memantine appears to have dose- and interval-dependent effects on sensorimotor gating in rats and humans, particularly among specific subgroups of normal human subjects. These findings are discussed as they relate to consistencies across other studies in humans, as well as apparent inconsistencies in the NMDA regulation of PPI across species

Substring filtering for low-cost linked data interfaces

Recently, Triple Pattern Fragments (TPFS) were introduced as a low-cost server-side interface when high numbers of clients need to evaluate SPARQL queries. Scalability is achieved by moving part of the query execution to the client, at the cost of elevated query times. Since the TPFS interface purposely does not support complex constructs such as SPARQL filters, queries that use them need to be executed mostly on the client, resulting in long execution times. We therefore investigated the impact of adding a literal substring matching feature to the TPFS interface, with the goal of improving query performance while maintaining low server cost. In this paper, we discuss the client/server setup and compare the performance of SPARQL queries on multiple implementations, including Elastic Search and case-insensitive FM-index. Our evaluations indicate that these improvements allow for faster query execution without significantly increasing the load on the server. Offering the substring feature on TPF servers allows users to obtain faster responses for filter-based SPARQL queries. Furthermore, substring matching can be used to support other filters such as complete regular expressions or range queries

Combined endo-β-1,4-xylanase and α-L-arabinofuranosidase increases butyrate concentration during broiler cecal fermentation of maize glucurono-arabinoxylan

Solubilisation of prebiotic arabinoxylooligosaccharides from complex arabinoxylans in e.g. maize by xylanases may be increased by addition of auxiliary debranching enzymes. In this study, the hydrolysis and fermentation of maize fibre was investigated in vitro using a xylanase and an alpha-L-arabinofuranosidase. Combining the enzymes induced a higher (P < .001) xylose solubilisation and higher (P < .05) butyrate production during in vitro fermentation of maize fibre with cecal broiler inoculum compared to applying enzymes separately after 48 h. Subsequently, fibre degradation and fermentation was investigated in ROSS 308 broiler chickens supplemented with the enzyme combination to test the effects on gut morphology and microbiota composition along with performance. However, to address the relevance of combining the enzymes in vivo, further full factorial studies using individual enzymes at lower dosages are needed. Birds were fed a maize/soy based diet with 100 g/kg maize DDGS and 50 g/kg rapeseed meal. Enzymes supplementation increased (P < .001) body weight (+ 5.4%) and improved (P < .001) feed conversion ratio (-5.8%) after 29 days compared to control birds. Non-starch polysaccharide analysis and confocal microscopy of jejunum digesta visualised and confirmed solubilisation of the insoluble maize (glucurono)arabinoxylan. Birds receiving enzyme supplementation had increased (P < .001) duodenum villi length (+120 mu m) and reduced (P < .002) CD3 T-cell infiltration (-22.1%) after 29 days. Cecal butyrate levels were increased (P < .05) compared to controls. Although the microbiota composition was not significantly altered, numerical increases in cecal Ruminococcaceae and Lachnospiraceae genera were observed in birds supplemented with enzymes

What Automated Planning Can Do for Business Process Management

Business Process Management (BPM) is a central element of today organizations. Despite over the years its main focus has been the support of processes in highly controlled domains, nowadays many domains of interest to the BPM community are characterized by ever-changing requirements, unpredictable environments and increasing amounts of data that influence the execution of process instances. Under such dynamic conditions, BPM systems must increase their level of automation to provide the reactivity and flexibility necessary for process management. On the other hand, the Artificial Intelligence (AI) community has concentrated its efforts on investigating dynamic domains that involve active control of computational entities and physical devices (e.g., robots, software agents, etc.). In this context, Automated Planning, which is one of the oldest areas in AI, is conceived as a model-based approach to synthesize autonomous behaviours in automated way from a model. In this paper, we discuss how automated planning techniques can be leveraged to enable new levels of automation and support for business processing, and we show some concrete examples of their successful application to the different stages of the BPM life cycle

Prediction of Lifetime and 10-Year Risk of Cancer in Individual Patients With Established Cardiovascular Disease

BACKGROUND: Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer. OBJECTIVES: The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD. METHODS: Data from patients with established CVD from the UCC-SMART cohort (N ¼ 7,280) were used for model development, and from the CANTOS trial (N ¼ 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer. RESULTS: Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer. CONCLUSIONS: Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening

Telemetry tails: a practical method for attaching animal-borne devices to small vertebrates in the field

Context. Continued miniaturisation of tracking technology increases its utility in animal applications. However, species morphology often dictates the type of animal-borne device (ABD) that can be used, and how it is attached. The morphology of species within Peramelemorphia preclude them from the standard collar attachment of ABDs for terrestrial mammals. Aims. This paper describes a method for the tail-mount attachment of ABDs, and deployment results for Peramelemorphia across arid, semi-arid and temperate Australia to (a) test the performance of attachments and ABDs in the field and (b) discuss the animal welfare considerations for this attachment method. Methods. Tail-mount attachment of ABDs were field-tested on a total of 80 greater bilbies (Macrotis lagotis), and 14 long-nosed bandicoots (Perameles nasuta). Key results. Time to natural detachment (TTND) was between 2 and 52 days, with 65.74% (142 of 216) remaining on until manual removal. For ABDs that were manually removed, attachments were retained for up to 94 days. The method used for tail-mount attachment of ABDs to long-nosed bandicoots resulted in significantly shorter TTND compared with the method used for bilbies, and environmental factors (high temperatures and rainfall) had a negative effect on TTND. Tail-mount attached global positioning system (GPS) sensors collected large quantities of accurate data, with a maximum fix success rate of 83.38%. Damage to GPS (antenna breakage and water ingress) during deployment, however, impacted performance. In environments with frequent rainfall and waterlogged soils, the tape on a small proportion (6.25%) of (n = 192)attachments to bilbies caused tail injury. All injuries were resolvable, with most requiringminimal to no veterinary intervention. Key conclusions. Attachment longevity can be affectedby how the ABD is mounted to the tail, the species and the deployment environment. Theenvironment can also affect which adhesive tapes are suitable for ABD attachment. However, thismethod is highly modifiable, practical for field application and can have long retention timesrelative to other temporary methods. Implications. This ABD tail-mount attachment methodadds another tool to the telemetry tool-kit, with all the benefits of a low-tech, low-cost, passivedrop-off type attachment. This method has demonstrated practicality for Peramelemorphia, withpotential application to other suitable small vertebrates

The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis

In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death

Estimating body composition in adolescent sprint athletes : comparison of different methods in a 3 years longitudinal design

A recommended field method to assess body composition in adolescent sprint athletes is currently lacking. Existing methods developed for non-athletic adolescents were not longitudinally validated and do not take maturation status into account. This longitudinal study compared two field methods, i.e., a Bio Impedance Analysis (BIA) and a skinfold based equation, with underwater densitometry to track body fat percentage relative to years from age at peak height velocity in adolescent sprint athletes. In this study, adolescent sprint athletes (34 girls, 35 boys) were measured every 6 months during 3 years (age at start = 14.8 +/- 1.5yrs in girls and 14.7 +/- 1.9yrs in boys). Body fat percentage was estimated in 3 different ways: 1) using BIA with the TANITA TBF 410; 2) using a skinfold based equation; 3) using underwater densitometry which was considered as the reference method. Height for age since birth was used to estimate age at peak height velocity. Cross-sectional analyses were performed using repeated measures ANOVA and Pearson correlations between measurement methods at each occasion. Data were analyzed longitudinally using a multilevel cross-classified model with the PROC Mixed procedure. In boys, compared to underwater densitometry, the skinfold based formula revealed comparable values for body fatness during the study period whereas BIA showed a different pattern leading to an overestimation of body fatness starting from 4 years after age at peak height velocity. In girls, both the skinfold based formula and BIA overestimated body fatness across the whole range of years from peak height velocity. The skinfold based method appears to give an acceptable estimation of body composition during growth as compared to underwater densitometry in male adolescent sprinters. In girls, caution is warranted when interpreting estimations of body fatness by both BIA and a skinfold based formula since both methods tend to give an overestimation

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine