NICMOS Imaging of the HR 4796A Circumstellar Disk

We report the first near infrared (NIR) imaging of a circumstellar annular disk around the young (~8 Myr), Vega-like star, HR 4796A. NICMOS coronagraph observations at 1.1 and 1.6 microns reveal a ring-like symmetrical structure peaking in reflected intensity 1.05 arcsec +/- 0.02 arcsec (~ 70 AU) from the central A0V star. The ring geometry, with an inclination of 73.1 deg +/- 1.2 deg and a major axis PA of 26.8 deg +/- 0.6 deg, is in good agreement with recent 12.5 and 20.8 micron observations of a truncated disk (Koerner, et al. 1998). The ring is resolved with a characteristic width of less than 0.26 arcsec (17 AU) and appears abruptly truncated at both the inner and outer edges. The region of the disk-plane inward of ~60 AU appears to be relatively free of scattering material. The integrated flux density of the part of the disk that is visible (greater than 0.65 arcsec from the star) is found to be 7.5 +/- 0.5 mJy and 7.4 +/- 1.2 mJy at 1.1 and 1.6 microns, respectively. Correcting for the unseen area of the ring yields total flux densities of 12.8 +/- 1.0 mJy and 12.5 +/- 2.0 mJy, respectively (Vega magnitudes = 12.92 /+- 0.08 and 12.35 +/-0.18). The NIR luminosity ratio is evaluated from these results and ground-based photometry of the star. At these wavelengths Ldisk(lambda)/L*(lambda) = 1.4 +/- 0.2E-3 and 2.4 +/- 0.5E-3, giving reasonable agreement between the stellar flux scattered in the NIR and that which is absorbed in the visible and re-radiated in the thermal infrared. The somewhat red reflectance of the disk at these wavelengths implies mean particle sizes in excess of several microns, larger than typical interstellar grains. The confinement of material to a relatively narrow annular zone implies dynamical constraints on the disk particles by one or more as yet unseen bodies.Comment: 14 pages, 1 figure for associated gif file see: http://nicmosis.as.arizona.edu:8000/AAS99/FIGURE1_HR4796A_ApJL.gif . Accepted 13 January 1999, Astrophyical Journal Letter

The façade of power and the power of the façade:Memory and meaning in Victorian cities

Terraces and tenements provide the facades upon which are inscribed texts and decorative images. Embedded in the walls, these ‘plaques’ convey meanings and memories that saturate the built environment with references to the past. Evidence based on property based surveys, maps and archival documents form the empirical basis from which it is concluded that images and inscriptions presented a wider geo-political and historical awareness in the everyday setting of local residents. <br/

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials. Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules. Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (&gt;6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma. Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly

Designing a brief behaviour change intervention to reduce sexually transmitted infections: a discrete choice experiment

Objectives: To understand whether people attending sexual health (SH) clinics are willing to participate in a brief behavioural change intervention (BBCI) to reduce the likelihood of future sexually transmitted infections (STIs) and to understand their preferences for different service designs. Methods: A discrete choice experiment (DCE) with young heterosexual adults (aged 16-25 years), and men who have sex with men (MSM) aged 16 or above, attending SH clinics in England. Results: Data from 368 participants showed that people particularly valued BBCIs that involved talking (OR 1.45; 95%CI 1.35, 1.57 compared with an ‘email or text’ based BBCI), preferably with a health care professional rather than a peer. Findings also showed that 26% of respondents preferred ‘email / texts’ to all other options; the remaining 14% preferred not to participate in any of the offered BBCIs. Implications: These results suggest that most people attending SH clinics in England are likely to participate in a BBCI if offered, but the type / format of the BBCI is likely to be the single important determinant of uptake rather than characteristics such as the length and the number of sessions. Moreover, participants generally favoured ‘talking’ based options rather than digital alternatives, which are likely to require the most resources to implement

Platelet Glycoprotein lib: Chromosomal Localization and Tissue Expression

The GPIIb-IIIa complex functions as a receptor for cytoadhesive proteins on the platelet surface. Both GPIIb and GPIIIa are synthesized by a human erythroleukemia (HEL) cell line. We isolated several cDNA clones by screening a HEL cell cDNA library with an oligonucleotide derived from amino acid sequence of GPIIb. Nucleotide and amino acid sequences were determined from 703 bp of one of these clones. Amino acid sequence of purified platelet GPIIb peptides confirmed the identity of the clone. The cDNA encodes the carboxyl terminus of the large (a) subunit of GPIIb and all of the smaller (f6) subunit of GPIIb. By hybridizing the cDNA directly to chromosomes separated by dual laser chromosome sorting, the gene for GPIIb was mapped to chromosome 17. Northern blot analysis showed a - 3.4-kb GPIIb mRNA in HEL cells. We also compared the amino acid sequences determined from eight additional platelet GPIIb peptides with the derived amino acids from a published HEL cell GPIIb cDNA, and the platelet and HEL cell proteins appear to be the same. Despite previous reports that vascular endothelial cells and monocytes contain GPIIb, no GPIIb mRNA was observed in either type of cell. Thus, GPIIb appears to be specific for the platelet-megakaryocyte membrane and is distinct from the a subunits of the adhesion receptors in other normal tissues

Impact of Knowledge Based Information Systems on Organisations

This paper investigates the impact of knowledge based information systems (KBIS) on commercial organisations. A questionnaire and interview format was used to gather information from eleven commercial organisations developing KBIS. Three prime areas were considered, namely knowledge acquisition, knowledge representation, and KBIS development methodologies. For each of these areas, the normative position as expressed in the literature is presented and then compared to the survey findings. Problems involved in the development of KBIS are mentioned as well as developers’ perceptions of the future directions for KBIS within their organisations. Additional information on each organisation is presented in an Appendix in order to provide a richer picture and background to the study. The main preliminary findings are that KBIS have made an impact on organisations in Australia who are willing to make a considerable investment of resources in this new venture. While most organisations are treating this technology as research and development, they believe that the technology will be absorbed into their mainstream information systems in the future. These systems are seen as providing a competitive edge to those organisations willing to make the investment

Healthcare provider and service user perspectives on STI risk reduction interventions for young people and MSM in the UK

Objective Behavioural interventions have been shown to reduce sexual behaviours associated with increased risk of sexually transmitted infections in young people (<25 years) and men who have sex with men (MSM) internationally, but evidence from England is limited. We aimed to explore service provider and user experiences and perspectives on behavioural interventions to reduce sexual behaviour risks, and the use of automated methods to triage individuals to these services. Methods We conducted a sequential mixed methods study with sexual health service providers and users in 2015/2016. Qualitative interviews with providers and service users (heterosexual young people and MSM) in London and Brighton allowed us to explore a range of experiences and expectations. A subsequent national web-survey of service providers measured the feasibility of delivery within existing resources and preferences for intervention attributes. Results We conducted 35 service user (15 heterosexual young people; 20 MSM), and 26 provider interviews, and had 100 web-survey responses. We found considerable heterogeneity in prevention services offered. Service users and providers were broadly supportive of tailoring interventions offered, but service users raised concerns about automated, data-driven triage, particularly around equity and fairness of service delivery. Digital technologies, including social media or apps, were appealing to providers, being less resource intensive. However, one-to-one talking interventions remained popular with both service users and providers, being familiar, trust-worthy, and personal. Key tensions between desirability of interventions and availability of resources to deliver them was acknowledged/recognised by providers and users. Conclusion Overall, behavioural interventions to reduce sexual behaviour risks were viewed favourably by service providers and users, with key considerations including: privacy, personalisation and convenience. However, introducing desirable targeted interventions within heterogeneous sexual health settings will require resources to adapt interventions and research to fully understand the barriers and facilitators to use within routine services