The Slowly Formed Guiselin Brush

We study polymer layers formed by irreversible adsorption from a polymer melt. Our theory describes an experiment which is a ``slow'' version of that proposed by Guiselin [Europhys. Lett., v. 17 (1992) p. 225] who considered instantaneously irreversibly adsorbing chains and predicted a universal density profile of the layer after swelling with solvent to produce the ``Guiselin brush.'' Here we ask what happens when adsorption is not instantaneous. The classic example is chemisorption. In this case the brush is formed slowly and the final structure depends on the experiment's duration, $t_{final}$. We find the swollen layer consists of an inner region of thickness $z^* \sim t_{final}^{-5/3}$ with approximately constant density and an outer region extending up to height $h \sim N^{5/6}$ which has the same density decay $\sim z^{-2/5}$ as for the Guiselin case.Comment: 7 pages, submitted to Europhysics Letter

Additional collection devices used in conjunction with the SurePath Liquid-Based Pap Test broom device do not enhance diagnostic utility

BACKGROUND: We have previously shown that use of an EC brush device in combination with the Rovers Cervex-Brush (SurePath broom) offered no significant improvement in EC recovery. Here we determine if use of additional collection devices enhance the diagnostic utility of the SurePath Pap for gynecologic cytology. METHODS: After informed consent, 37 women ages 18–56 receiving their routine cervical examinations were randomized into four experimental groups. Each group was first sampled with the SurePath broom then immediately re-sampled with an additional collection device or devices. Group 1: Rover endocervix brush (n = 8). Group 2: Medscand CytoBrush Plus GT (n = 7). Group 3: Rover spatula + endocervix brush (n = 11). Group 4: Medscand spatula + CytoBrush Plus GT (n = 11). RESULTS: Examination of SurePath broom-collected cytology yielded the following abnormal diagnoses: atypia (n = 2), LSIL (n = 5) and HSIL (n = 3). Comparison of these diagnoses to those obtained from paired samples using the additional collection devices showed that use of a second and or third device yielded no additional abnormal diagnoses. Importantly, use of additional devices did not improve upon the abnormal cell recovery of the SurePath broom and in 4/10 cases under-predicted or did not detect the SurePath broom-collected lesion as confirmed by cervical biopsy. Finally, in 36/37 cases, the SurePath broom successfully recovered ECs. Use of additional devices, in Group 3, augmented EC recovery to 37/37. CONCLUSIONS: Use of additional collection devices in conjunction with the SurePath broom did not enhance diagnostic utility of the SurePath Pap. A potential but not significant improvement in EC recovery might be seen with the use of three devices

Compact Binary Coalescences in the Band of Ground-based Gravitational-Wave Detectors

As the ground-based gravitational-wave telescopes LIGO, Virgo, and GEO 600 approach the era of first detections, we review the current knowledge of the coalescence rates and the mass and spin distributions of merging neutron-star and black-hole binaries. We emphasize the bi-directional connection between gravitational-wave astronomy and conventional astrophysics. Astrophysical input will make possible informed decisions about optimal detector configurations and search techniques. Meanwhile, rate upper limits, detected merger rates, and the distribution of masses and spins measured by gravitational-wave searches will constrain astrophysical parameters through comparisons with astrophysical models. Future developments necessary to the success of gravitational-wave astronomy are discussed.Comment: Replaced with version accepted by CQG

A mechanistic target of rapamycin complex 1/2 (mTORC1)/V-Akt murine thymoma viral oncogene homolog 1 (AKT1)/cathepsin H axis controls filaggrin expression and processing in skin, a novel mechanism for skin barrier disruption in patients with atopic dermatitis

BACKGROUND: Filaggrin, encoded by the FLG gene, is an important component of the skin’s barrier to the external environment and genetic defects in FLG strongly associate with Atopic Dermatitis (AD). However, not all AD patients have FLG mutations. OBJECTIVE: We hypothesised that these patients may possess other defects in filaggrin expression and processing, contributing to barrier disruption and AD, and therefore present novel therapeutic targets for this disease. RESULTS: We describe the relationship between the mTORC1 protein subunit RAPTOR, the serine/threonine kinase AKT1 and the protease cathepsin H, for which we establish a role in filaggrin expression and processing. Increased RAPTOR levels correlated with decreased filaggrin expression in AD. In keratinocyte cell culture, RAPTOR up-regulation or AKT1 shRNA knockdown reduced the expression of the protease cathepsin H. Skin of cathepsin H-deficient mice and CTSH shRNA knockdown keratinocytes showed reduced filaggrin processing and the mouse showed both impaired skin barrier function and a mild proinflammatory phenotype. CONCLUSION: Our findings highlight a novel, potentially treatable, signalling axis controlling filaggrin expression and processing which is defective in AD

Safety and tolerability of etirinotecan pegol in advanced breast cancer: analysis of the randomized, phase 3 BEACON trial

Purpose: New treatments with novel mechanisms of action and non-overlapping toxicities are needed for patients with metastatic breast cancer. Etirinotecan pegol (EP) is a long-acting topoisomerase-I inhibitor with a unique toxicity profile. The randomized phase 3 BEACON study that compared EP to treatment of physician’s choice (TPC) demonstrated its clinical activity. We now present detailed safety data from the BEACON trial. Methods: Patients with locally recurrent or metastatic breast cancer who had received at least two prior cytotoxic regimens for advanced disease were randomized to EP or TPC. Prior treatment with an anthracycline, a taxane and capecitabine was required. The frequencies of treatment-emergent AEs (TEAEs) and serious TEAEs were evaluated for the safety population, comprising all patients who received at least one dose of assigned treatment. Results: A total of 831 patients were evaluated (n = 425, EP; n = 406, TPC). Compared with TPC, EP was associated with a slightly higher median relative dose intensity (98.3 vs. 92.8 %, respectively) and significantly fewer grade ≥3 toxicities (48.0 vs. 63.1 %, P < 0.0001). The most commonly reported grade ≥3 toxicities in the EP arm were diarrhea (9.6 %) and neutropenia (9.6 %) and in the TPC arm, neutropenia (30.8 %). Median time to onset of grade ≥3 diarrhea was delayed with EP relative to TPC (43 vs. 7 days, respectively). Conclusions: The differentiated mechanism of action of EP resulted in a safety profile that is substantially distinguished from that of current widely used therapies for the treatment of women with advanced breast cancer

The effects of LIGO detector noise on a 15-dimensional Markov-chain Monte-Carlo analysis of gravitational-wave signals

Gravitational-wave signals from inspirals of binary compact objects (black holes and neutron stars) are primary targets of the ongoing searches by ground-based gravitational-wave (GW) interferometers (LIGO, Virgo, and GEO-600). We present parameter-estimation results from our Markov-chain Monte-Carlo code SPINspiral on signals from binaries with precessing spins. Two data sets are created by injecting simulated GW signals into either synthetic Gaussian noise or into LIGO detector data. We compute the 15-dimensional probability-density functions (PDFs) for both data sets, as well as for a data set containing LIGO data with a known, loud artefact ("glitch"). We show that the analysis of the signal in detector noise yields accuracies similar to those obtained using simulated Gaussian noise. We also find that while the Markov chains from the glitch do not converge, the PDFs would look consistent with a GW signal present in the data. While our parameter-estimation results are encouraging, further investigations into how to differentiate an actual GW signal from noise are necessary.Comment: 11 pages, 2 figures, NRDA09 proceeding

The silence of self-knowledge

Gareth Evans famously affirmed an explanatory connection between answering the question whether p and knowing whether one believes that p. This is commonly interpreted in terms of the idea that judging that p constitutes an adequate basis for the belief that one believes that p. This paper formulates and defends an alternative, more modest interpretation, which develops from the suggestion that one can know that one believes that p in judging that p