Clinical Study Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy

Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391

Efficacy and Tolerability of Travoprost 0.004 %

Objective. To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods. In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results. The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5±2.5 mmHg and 22.2±2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7±3.1 mmHg and 16.1±3.1 mmHg, respectively, in TTFC group and 21.1±3.1 mmHg and 16.1±2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (−4.6 mmHg; one-sided 95% confidence interval [−inf, −3.9]; p<0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion. Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391

Gravitational Lensing at Millimeter Wavelengths

With today's millimeter and submillimeter instruments observers use gravitational lensing mostly as a tool to boost the sensitivity when observing distant objects. This is evident through the dominance of gravitationally lensed objects among those detected in CO rotational lines at z>1. It is also evident in the use of lensing magnification by galaxy clusters in order to reach faint submm/mm continuum sources. There are, however, a few cases where millimeter lines have been directly involved in understanding lensing configurations. Future mm/submm instruments, such as the ALMA interferometer, will have both the sensitivity and the angular resolution to allow detailed observations of gravitational lenses. The almost constant sensitivity to dust emission over the redshift range z=1-10 means that the likelihood for strong lensing of dust continuum sources is much higher than for optically selected sources. A large number of new strong lenses are therefore likely to be discovered with ALMA, allowing a direct assessment of cosmological parameters through lens statistics. Combined with an angular resolution <0.1", ALMA will also be efficient for probing the gravitational potential of galaxy clusters, where we will be able to study both the sources and the lenses themselves, free of obscuration and extinction corrections, derive rotation curves for the lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on "Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be published by Springer-Verlag 2002. Paper with full resolution figures can be found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g

Role of PACAP and VIP Signalling in Regulation of Chondrogenesis and Osteogenesis

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are multifunctional proteins that can regulate diverse physiological processes. These are also regarded as neurotrophic and anti-inflammatory substances in the CNS, and PACAP is reported to prevent harmful effects of oxidative stress. In the last decade more and more data accumulated on the similar function of PACAP in various tissues, but its cartilage- and bone-related presence and functions have not been widely investigated yet. In this summary we plan to verify the presence and function of PACAP and VIP signalling tool kit during cartilage differentiation and bone formation. We give evidence about the protective function of PACAP in cartilage regeneration with oxidative or mechanically stress and also with the modulation of PACAP signalling in vitro in osteogenic cells. Our observations imply the therapeutic perspective that PACAP might be applicable as a natural agent exerting protecting effect during joint inflammation and/or may promote cartilage regeneration during degenerative diseases of articular cartilage

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements