Improved timed-mating, non-invasive method using fewer unproven female rats with pregnancy validation via early body mass increases

For studies requiring accurate conception-timing, reliable, efficient methods of detecting oestrus reduce time and costs, whilst improving welfare. Standard methods use vaginal cytology to stage cycle, and breeders are paired–up using approximately five proven females with proven males to achieve at least one conception on a specific day. We describe an alternative, fast, consistent, non-invasive method of timed-mating using detection of lordosis behaviour in Wistar and Lister-Hooded rats that used unproven females with high success rates. Rats under reverse-lighting had body masses recorded pre-mating, day (d) 3-4, d8, d10 and d18 of pregnancy. Using only the presence of the oestrus dance to time-mate females for 24-hrs, 89% Wistar and 88% Lister-Hooded rats successfully conceived. We did not observe behavioural oestrus in Sprague-Dawleys without males present. Significant body mass increases following mating distinguished pregnant from non-pregnant rats, as early as d4 of pregnancy (10% ± 1.0 increase cf 3% ± 1.2). The pattern of increases throughout gestation was similar for all pregnant rats until late pregnancy, when there were smaller increases for primi- and multiparous rats (32% ± 2.5; 25% ± 2.4), whereas nulliparous rats had highest gains (38% ± 1.5). This method demonstrated a distinct refinement of the previous timed-mating common practice used, as disturbance of females was minimised. Only the number required of nulli-, primi- or multiparous rats were mated, and body mass increases validated pregnancy status. This new breeding-management method is now established practice for two strains of rat and resulted in a reduction in animal use

High-resolution laboratory lysimeter for automated sampling of tracers through a 0.5m soil block

A computer-controlled, automated sample collection from a 0.5-m lysimeter, designed to give superior temporal and spatial resolution for monitoring the movement of chemical tracers through a large undisturbed soil block, is described. The soil block, 0.520.520.5 m, was monitored for saturation using eight time domain reflectometry probes. Rainfall was applied at approximately 1600 ml hm1 using a 12212 array of 23-gauge (0.318 mm internal diameter) hypodermic needles. Soil leachates were collected at the base of the soil block using a machined aluminium collection plate with a 10210 grid of funnels that passed leachates to sample collection palettes. Sample collection was automated using a personal computer equipped with National Instruments LabVIEW™ software and linked to sensors for palette tracking. The automation of the lysimeter allowed sample collection and storage over a user-defined period with no human interaction. As an example of the use of the automated lysimeter, results show the distribution of phosphate within the soil. The eluted phosphate showed an initial and secondary peak, and only emerged from preferential flow channels

Utility of palliative EUS-guided biliary drainage using lumen-apposing metal stents: a prospective multicenter feasibility study (with video)

BACKGROUND AND AIMS: Biliary drainage with ERCP is successful in only 80% to 90% of extrahepatic cholangiocarcinoma and pancreatic cancer. We present the results of a multicenter prospective study assessing the safety, feasibility, and quality of life of patients after EUS-guided biliary drainage (EUS-BD) with lumen-apposing metal stents (LAMSs), after failed ERCP. METHODS: All consecutive adults with a dilated common bile duct (CBD) ≥14 mm secondary to inoperable malignant distal common bile duct (CBD) stricture and failed ERCP biliary drainage were screened and recruited from 3 tertiary U.K. centers. Technical success of EUS-BD using LAMSs was the primary endpoint. Improvement in serum bilirubin, 30-day mortality, procedure-related adverse events, and quality of life were secondary endpoints. The quality of life improvement was measured using a validated questionnaire (EORTC QLQ-BIL21). RESULTS: Twenty patients were included in analysis. EUS-BD was technically successful in all patients and the clinical success was 95% (19/20) at day 7 (>50% reduction in bilirubin) and 92.3% (12/13) at day 30 (bilirubin <50 μmol/L). There were significant improvements in overall quality of life score (49 vs 42, p=0.03) at day 30. All cause 30-day mortality was 20% and the moderate adverse event rate was 10% (1 cholangitis and 1 stent migration). CONCLUSION: EUS-BD has acceptable technical success and safety as a second line palliative treatment for inoperable malignant distal CBD strictures. Randomized controlled studies comparing EUS-BD with percutaneous transhepatic biliary drainage (PTBD) are needed to determine their effectiveness in clinical practice

Reasoning from connectives and relations between entities

This article reports investigations of inferences that depend both on connectives between clauses, such as or else, and on relations between entities, such as in the same place as. Participants made more valid inferences from biconditionals—for instance, Ann is taller than Beth if and only if Beth is taller than Cath—than from exclusive disjunctions (Exp. 1). They made more valid transitive inferences from a biconditional when a categorical premise affirmed rather than denied one of its clauses, but they made more valid transitive inferences from an exclusive disjunction when a categorical premise denied rather than affirmed one of its clauses (Exp. 2). From exclusive disjunctions, such as Either Ann is not in the same place as Beth or else Beth is not in the same place as Cath, individuals tended to infer that all three individuals could be in different places, whereas in fact this was impossible (Exps. 3a and 3b). The theory of mental models predicts all of these results

Strategies used as spectroscopy of financial markets reveal new stylized facts

We propose a new set of stylized facts quantifying the structure of financial markets. The key idea is to study the combined structure of both investment strategies and prices in order to open a qualitatively new level of understanding of financial and economic markets. We study the detailed order flow on the Shenzhen Stock Exchange of China for the whole year of 2003. This enormous dataset allows us to compare (i) a closed national market (A-shares) with an international market (B-shares), (ii) individuals and institutions and (iii) real investors to random strategies with respect to timing that share otherwise all other characteristics. We find that more trading results in smaller net return due to trading frictions. We unveiled quantitative power laws with non-trivial exponents, that quantify the deterioration of performance with frequency and with holding period of the strategies used by investors. Random strategies are found to perform much better than real ones, both for winners and losers. Surprising large arbitrage opportunities exist, especially when using zero-intelligence strategies. This is a diagnostic of possible inefficiencies of these financial markets.Comment: 13 pages including 5 figures and 1 tabl

Process Mining of Disease Trajectories: A Literature Review

Disease trajectories model patterns of disease over time and can be mined by extracting diagnosis codes from electronic health records (EHR). Process mining provides a mature set of methods and tools that has been used to mine care pathways using event data from EHRs and could be applied to disease trajectories. This paper presents a literature review on process mining related to mining disease trajectories using EHRs. Our review identified 156 papers of potential interest but only four papers which directly applied process mining to disease trajectory modelling. These four papers are presented in detail covering data source, size, selection criteria, selections of the process mining algorithms, trajectory definition strategies, model visualisations, and the methods of evaluation. The literature review lays the foundations for further research leveraging the established benefits of process mining for the emerging data mining of disease trajectories

Escherichia coli Bacteriocins: Antimicrobial Efficacy and Prevalence among Isolates from Patients with Bacteraemia

Bacteriocins are antimicrobial peptides generally active against bacteria closely related to the producer. Escherichia coli produces two types of bacteriocins, colicins and microcins. The in vitro efficacy of isolated colicins E1, E6, E7, K and M, was assessed against Escherichia coli strains from patients with bacteraemia of urinary tract origin. Colicin E7 was most effective, as only 13% of the tested strains were resistant. On the other hand, 32%, 33%, 43% and 53% of the tested strains exhibited resistance to colicins E6, K, M and E1. Moreover, the inhibitory activity of individual colicins E1, E6, E7, K and M and combinations of colicins K, M, E7 and E1, E6, E7, K, M were followed in liquid broth for 24 hours. Resistance against individual colicins developed after 9 hours of treatment. On the contrary, resistance development against the combined action of 5 colicins was not observed. One hundred and five E. coli strains from patients with bacteraemia were screened by PCR for the presence of 5 colicins and 7 microcins. Sixty-six percent of the strains encoded at least one bacteriocin, 43% one or more colicins, and 54% one or more microcins. Microcins were found to co-occur with toxins, siderophores, adhesins and with the Toll/Interleukin-1 receptor domain-containing protein involved in suppression of innate immunity, and were significantly more prevalent among strains from non-immunocompromised patients. In addition, microcins were highly prevalent among non-multidrug-resistant strains compared to multidrug-resistant strains. Our results indicate that microcins contribute to virulence of E. coli instigating bacteraemia of urinary tract origin