A comparison between omeprazole and a dietary supplement for the management of squamous gastric ulceration in horses

Although several studies have assessed the short-term effect of dietary supplements on the treatment and prevention of gastric ulceration in horses, few have assessed the response over a duration of more than 30 days. A blinded randomized noninferiority clinical trial was conducted using 42 Thoroughbred horses in race training with squamous ulceration of ≥ grade 2/4, randomly assigned to one of two treatment groups for a period of 90 days: omeprazole at the full label dose of 4 mg/kg or the Succeed digestive conditioning supplement. Noninferiority analyses and Wilcoxon sign rank tests were used to analyze the data. At day 90, Succeed was noninferior to 4 mg/kg omeprazole administered daily in terms of the proportion of horses with complete resolution of squamous ulceration. At day 30, Succeed was found to be inferior to omeprazole in terms of the proportion of horses with grade ≤1/4 squamous ulceration. The proportion of horses with reducing squamous ulcer score (compared with day 0) was statistically significant for both treatments at days 30 and 60. At day 90 of the 17 horses on Succeed, nine had a reducing squamous ulcer score (P value = .049), and of the 19 horses on omeprazole, 10 had a reducing squamous ulcer score at day 90 (P value = .091). The noninferiority of Succeed compared to omeprazole at 90 days for the complete resolution of squamous ulceration and the reduced efficacy of omeprazole following 90 days of treatment are likely to be of interest to practitioners managing gastric ulceration in performance horses

Terugblik op mijn loopbaan in de psychiatrie. Voordrachten, geselecteerde teksten en een autobiografische schets

Dit eboek bestaat uit een selectie van voordrachten en publicaties van prof. dr. Harry G.M. Rooijmans (1937-2013), aangevuld met een autobiografische schets. Prof. Rooijmans bezette gedurende 23 jaar – van 1976 tot 1999 – de leerstoel klinische psychiatrie in Leiden. Vanaf zijn opleidingstijd in de zestiger jaren tot zijn emeritaat in 1999 heeft zich in de psychiatrie een paradigma wisseling voltrokken, van het literair en psychoanalytisch denken van weleer naar de evidence-based praktijk van vandaag. Harry Rooijmans was zich als geen ander bewust van de veranderingen en hij heeft er ook zijn steentje aan bijgedragen. Zijn Leidse school van “Nuchtere Psychiatrie” heeft haar sporen nagelaten in het grote aantal psychiaters, bestuurders en hoogleraren die in zijn geest zijn opgeleid. In deze selectie van teksten geeft hij zijn visie geeft op verschillende aspecten van de ontwikkeling van de psychiatrie. Als zodanig is het een belangrijk tijdsdocument over de evolutie van de Nederlandse psychiatrie.Wetensch. publicati

Assessing lung cancer screening programs under uncertainty in a heterogeneous population

Background: Lung cancer screening can reduce cancer mortality. Most implementation studies focus only on low-dose computed tomography (LDCT) and clinical attributes of screening and do not include preferences of potential participants. In this study we evaluated the perceived value of screening programs based on LDCT, breath analysis (BA), or blood biomarkers (BB) according to the perspective of the target population. Methods: A multi-criteria decision analysis framework was adopted. The weights of seven attributes of screening (sensitivity, specificity, radiation burden, duration of screening process, waiting time until results are communicated, location of screening, and mode of screening) were obtained from an earlier study that included a broad sample from the Netherlands. Performance data for the screening modalities was obtained from clinical trials and expert opinion. Parameter uncertainty about clinical performances was incorporated probabilistically, while heterogeneity in preferences was analyzed through subgroup analyses. Results: The mean overall values were 0.58 (CI: 0.57 to 0.59), 0.57 (CI: 0.56 to 0.59), and 0.44 (CI: 0.43 to 0.45) for BB, BA, and LDCT, respectively. Seventy-seven per cent of respondents preferred BB or BA. For most subgroups, the overall values were similar to those of the entire sample. BA had the highest value for respondents who would have been eligible for earlier screening trials. Discussion: BB and BA seem valuable to participants because they can be applied in a primary care setting. Although LDCT still seems preferable given its strong and positive evidence base, it is important to take non-clinical attributes into account to maximize attendance.</p

Synthesis, antimicrobial activities and GAPDH docking of novel 1, 2, 3-triazole derivatives

Purpose: To synthesize new triazole derivatives in order to overcome the problem of side effects of antimicrobial agents and microbial resistance, while broadening the spectrum of antimicrobial activity. Methods: The starting triazole, compound 1, was prepared through click chemistry and reacted with chloroacetyl chloride to yield compound II. Triazole 1 was reacted with acids and aldehydes to produce oxadiazole (III) and azomethine (IV) which cyclized in acetic anhydride to give a new acetylated oxadiazole (V). Minimum inhibitory concentration (MIC) and resorufin assays were used for antibacterial and anti-parasitic screening, respectively. Compounds II and IVb were subjected to molecular docking studies using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Molecular Operating Environment (MOE) program. Results: Novel oxazole-triazole derivative (III) showed high activity against Pseudomonas aeruginosa and moderate activity against Staphylococcus epidermidis, whereas compound IVc showed moderate activity against Staphylococcus epidermidis. Chloro-acetyl-triazole II and 2-hydroxyphenyl-triazole Schiff base (Ivb) showed pronounced activity against the kinetoplastid parasites, Leishmania major, Leishmania mexicana and Trypanosoma brucei. Conclusion: The new synthesized triazoles represent a new antimicrobial scaffold and identifies potential new lead compounds for follow-up and for further mechanistic studies

Gravitational waves from self-ordering scalar fields

Gravitational waves were copiously produced in the early Universe whenever the processes taking place were sufficiently violent. The spectra of several of these gravitational wave backgrounds on subhorizon scales have been extensively studied in the literature. In this paper we analyze the shape and amplitude of the gravitational wave spectrum on scales which are superhorizon at the time of production. Such gravitational waves are expected from the self ordering of randomly oriented scalar fields which can be present during a thermal phase transition or during preheating after hybrid inflation. We find that, if the gravitational wave source acts only during a small fraction of the Hubble time, the gravitational wave spectrum at frequencies lower than the expansion rate at the time of production behaves as $\Omega_{\rm GW}(f) \propto f^3$ with an amplitude much too small to be observable by gravitational wave observatories like LIGO, LISA or BBO. On the other hand, if the source is active for a much longer time, until a given mode which is initially superhorizon ($k\eta_* \ll 1$), enters the horizon, for $k\eta \gtrsim 1$, we find that the gravitational wave energy density is frequency independent, i.e. scale invariant. Moreover, its amplitude for a GUT scale scenario turns out to be within the range and sensitivity of BBO and marginally detectable by LIGO and LISA. This new gravitational wave background can compete with the one generated during inflation, and distinguishing both may require extra information.Comment: 21 pages, 2 figures, added discussion about numerical integration and a new figure to illustrate the scale-invariance of the GW power spectrum, conclusions unchange

Fluctuations in viscous fingering

Our experiments on viscous (Saffman-Taylor) fingering in Hele-Shaw channels reveal finger width fluctuations that were not observed in previous experiments, which had lower aspect ratios and higher capillary numbers Ca. These fluctuations intermittently narrow the finger from its expected width. The magnitude of these fluctuations is described by a power law, Ca^{-0.64}, which holds for all aspect ratios studied up to the onset of tip instabilities. Further, for large aspect ratios, the mean finger width exhibits a maximum as Ca is decreased instead of the predicted monotonic increase.Comment: Revised introduction, smoothed transitions in paper body, and added a few additional minor results. (Figures unchanged.) 4 pages, 3 figures. Submitted to PRE Rapi

Advanced technologies for future ground-based, laser-interferometric gravitational wave detectors

We present a review of modern optical techniques being used and developed for the field of gravitational wave detection. We describe the current state-of-the-art of gravitational waves detector technologies with regard to optical layouts, suspensions and test masses. We discuss the dominant sources and noise in each of these subsystems and the developments that will help mitigate them for future generations of detectors. We very briefly summarise some of the novel astrophysics that will be possible with these upgraded detectors

Comparison of advanced gravitational-wave detectors

We compare two advanced designs for gravitational-wave antennas in terms of their ability to detect two possible gravitational wave sources. Spherical, resonant mass antennas and interferometers incorporating resonant sideband extraction (RSE) were modeled using experimentally measurable parameters. The signal-to-noise ratio of each detector for a binary neutron star system and a rapidly rotating stellar core were calculated. For a range of plausible parameters we found that the advanced LIGO interferometer incorporating RSE gave higher signal-to-noise ratios than a spherical detector resonant at the same frequency for both sources. Spheres were found to be sensitive to these sources at distances beyond our galaxy. Interferometers were sensitive to these sources at far enough distances that several events per year would be expected

Modulation of human peripheral blood mononuclear cell signaling by medicinal cannabinoids

Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis. However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized. In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis. Healthy volunteers were asked to ingest medical cannabis, and kinome profiling was used to generate comprehensive descriptions of the cannabis challenge on inflammatory signal transduction in the peripheral blood of these volunteers. Results were related to both short term and long term effects in patients experimentally treated with a medical marijuana preparation for suffering from abdominal pain as a result of chronic pancreatitis or other causes. The results reveal an immunosuppressive effect of cannabinoid preparations via deactivation of signaling through the pro-inflammatory p38 MAP kinase and mTOR pathways and a concomitant deactivation of the pro-mitogenic ERK pathway. However, long term cannabis exposure in two patients resulted in reversal of this effect. While these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations