On the Nature of Scientific Progress: Anarchistic Theory Says “Anything Goes”—But I Don't Think So

Evolutionary biologist Axel Meyer reviews the new English translation of philosopher Paul Feyerabend's The Tyranny of Science

Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

Càncer de bufeta; Rucaparib; Carcinoma urotelialCáncer de vejiga; Rucaparib; Carcinoma urotelialBladder cancer; Rucaparib; Urothelial carcinomaBackground ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). Methods Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. Results Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. Conclusions Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.The work was supported by Clovis Oncology (no grant number) and was designed by the sponsor, P. Grivas, and S. Chowdhury

The Importance of Context and Cognitive Agency in Developing Police Knowledge: Going Beyond the Police Science Discourse

This paper argues the current exposition of police knowledge through the discourses of police science and evidenced based policing (EBP) leads to exaggerated claims about what is, and can be, known in policing. This new orthodoxy underestimates the challenges of applying knowledge within culturally-mediated police practice. The paper draws upon virtue epistemology highlighting the role cognitive agency plays in establishing knowledge claims. We challenge the assumption that it is possible to derive what works in all instances of certain aspects of policing and suggest it would be more apt to speak about what worked within a specific police context

Gravitational Energy Loss and Binary Pulsars in the Scalar Ether-Theory of Gravitation

Motivation is given for trying a theory of gravity with a preferred reference frame (``ether'' for short). One such theory is summarized, that is a scalar bimetric theory. Dynamics is governed by an extension of Newton's second law. In the static case, geodesic motion is recovered together with Newton's attraction field. In the static spherical case, Schwarzschild's metric is got. An asymptotic scheme of post-Minkowskian (PM) approximation is built by associating a conceptual family of systems with the given weakly-gravitating system. It is more general than the post-Newtonian scheme in that the velocity may be comparable with $c$. This allows to justify why the 0PM approximation of the energy rate may be equated to the rate of the Newtonian energy, as is usually done. At the 0PM approximation of this theory, an isolated system loses energy by quadrupole radiation, without any monopole or dipole term. It seems plausible that the observations on binary pulsars (the pulse data) could be nicely fitted with a timing model based on this theory.Comment: Text of a talk given at the 4th Conf. on Physics Beyond the Standard Model, Tegernsee, June 2003, submitted to the Proceedings (H. V. Klapdor-Kleingrothaus, ed.

Cotinine-assessed second-hand smoke exposure and risk of cardiovascular disease in older adults

Objectives: To examine whether second-hand smoke (SHS) exposure measured by serum cotinine is associated with increased coronary heart disease (CHD) and stroke risk among contemporary older British adults. Design: Prospective population-based study with self-reported medical history and health behaviours. Fasting blood samples were analysed for serum cotinine and cardiovascular disease (CVD) risk markers. Setting: Primary care centres in 25 British towns in 1998–2001. Patients: 8512 60–79-year-old men and women selected from primary care registers. Main outcome measures: Fatal and non-fatal myocardial infarction (MI; n=445) and stroke (n=386) during median 7.8-year follow-up. Main exposure: Observational study of serum cotinine assayed from fasting blood sample using liquid chromatography tandem mass spectrometry method, and self-reported smoking history. Results: Among 5374 non-smokers without pre-existing CVD, geometric mean cotinine was 0.15 ng/ml (IQR 0.05–0.30). Compared with non-smokers with cotinine ≤0.05 ng/ml, higher cotinine levels (0.06–0.19, 0.2–0.7 and 0.71–15.0 ng/ml) showed little association with MI; adjusted HRs were 0.92 (95% CI 0.63 to 1.35), 1.07 (0.73 to 1.55) and 1.09 (0.69 to 1.72), p(trend)=0.69. Equivalent HRs for stroke were 0.82 (0.55 to 1.23), 0.74 (0.48 to 1.13) and 0.69 (0.41 to 1.17), p(trend)=0.065. The adjustment for sociodemographic, behavioural and CVD risk factors had little effect on the results. The HR of MI for smokers (1–9 cigarettes/day) compared with non-smokers with cotinine ≤0.05 ng/ml was 2.14 (1.39 to 3.52) and 1.03 (0.52 to 2.04) for stroke. Conclusions: In contemporary older men and women, SHS exposure (predominantly at low levels) was not related to CHD or stroke risks, but we cannot rule out the possibility of modest effects at higher exposure levels

Hybrid simulation of Titan's interaction with the supersonic solar wind during Cassini's T96 flyby

By applying a hybrid (kinetic ions and fluid electrons) simulation code, we study the plasma environment of Saturn's largest moon Titan during Cassini's T96 flyby on 1 December 2013. The T96 encounter marks the only observed event of the entire Cassini mission where Titan was located in the supersonic solar wind in front of Saturn's bow shock. Our simulations can quantitatively reproduce the key features of Cassini magnetic field and electron density observations during this encounter. We demonstrate that the large-scale features of Titan's induced magnetosphere during T96 can be described in terms of a steady state interaction with a high-pressure solar wind flow. About 40 min before the encounter, Cassini observed a rotation of the incident solar wind magnetic field by almost 90°. We provide strong evidence that this rotation left a bundle of fossilized magnetic field lines in Titan's ionosphere that was subsequently detected by the spacecraft.Fil: Feyerabend, Moritz. Georgia Institute Of Techology; Estados UnidosFil: Simon, Sven. Georgia Institute Of Techology; Estados UnidosFil: Neubauer, Fritz M.. Universitat Zu Köln; AlemaniaFil: Motschmann, Uwe. Deutsches Zentrum Fur Luft- Und Raumfahrt; Alemania. Technische Universitat Braunschweig; AlemaniaFil: Bertucci, Cesar. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Edberg, Niklas J. T.. Instiutet For Rymdfysik; SueciaFil: Hospodarsky, George B.. University Of Iowa; Estados UnidosFil: Kurth, William S.. University Of Iowa; Estados Unido

A randomized-controlled trial of low-dose doxycycline for periodontitis in smokers

Background/Aim : Tobacco use reduces the effect of non-surgical periodontal therapy. Host-modulation with low-dose doxycycline (LDD) might favour repair and promote an improved treatment response. The aim of this study was to investigate the effect of LDD in smokers on non-surgical periodontal therapy. Material and Methods : This was a parallel arm, randomized, identical placebo-controlled trial with masking of examiner, care-giver, participant and statistician and 6 months of follow-up. Patients received non-surgical therapy and 3 months of test or control drug. Statistical analysis used both conventional methods and multilevel modelling. Results : Eighteen control and 16 test patients completed the study. The velocity of change was statistically greater for the test group for clinical attachment level −0.19 mm/month (95% CI=−0.34, 0.04; p =0.012) and probing depth 0.30 mm/month (95% CI=−0.42, −0.17; p <0.001). However, no differences were observed for absolute change in clinical or biochemical markers at 6 months. Conclusions : This study does not provide evidence of a benefit of using LDD as an adjunct to non-surgical periodontal therapy in smokers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74791/1/j.1600-051X.2007.01058.x.pd