The impact of accretion disc winds on the optical spectra of cataclysmic variables

Many high-state non-magnetic cataclysmic variables (CVs) exhibit blueshifted absorption or P-Cygni profiles associated with ultraviolet (UV) resonance lines. These features imply the existence of powerful accretion disc winds in CVs. Here, we use our Monte Carlo ionization and radiative transfer code to investigate whether disc wind models that produce realistic UV line profiles are also likely to generate observationally significant recombination line and continuum emission in the optical waveband. We also test whether outflows may be responsible for the single-peaked emission line profiles often seen in high-state CVs and for the weakness of the Balmer absorption edge (relative to simple models of optically thick accretion discs). We find that a standard disc wind model that is successful in reproducing the UV spectra of CVs also leaves a noticeable imprint on the optical spectrum, particularly for systems viewed at high inclination. The strongest optical wind-formed recombination lines are H alpha and He ii lambda 4686. We demonstrate that a higher density outflow model produces all the expected H and He lines and produces a recombination continuum that can fill in the Balmer jump at high inclinations. This model displays reasonable verisimilitude with the optical spectrum of RW Trianguli. No single-peaked emission is seen, although we observe a narrowing of the double-peaked emission lines from the base of the wind. Finally, we show that even denser models can produce a single-peaked H alpha line. On the basis of our results, we suggest that winds can modify, and perhaps even dominate, the line and continuum emission from CVs.

Developing the clinical components of a complex intervention for a glaucoma screening trial:a mixed methods study

BACKGROUND: Glaucoma is a leading cause of avoidable blindness worldwide. Open angle glaucoma is the most common type of glaucoma. No randomised controlled trials have been conducted evaluating the effectiveness of glaucoma screening for reducing sight loss. It is unclear what the most appropriate intervention to be evaluated in any glaucoma screening trial would be. The purpose of this study was to develop the clinical components of an intervention for evaluation in a glaucoma (open angle) screening trial that would be feasible and acceptable in a UK eye-care service.

METHODS: A mixed-methods study, based on the Medical Research Council (MRC) framework for complex interventions, integrating qualitative (semi-structured interviews with 46 UK eye-care providers, policy makers and health service commissioners), and quantitative (economic modelling) methods. Interview data were synthesised and used to revise the screening interventions compared within an existing economic model.

RESULTS: The qualitative data indicated broad based support for a glaucoma screening trial to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances. There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity) with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty.

CONCLUSIONS: Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.

Genomics and the impact of new technologies on the management of colorectal cancer

High-throughput genomic technologies have the potential to have a major impact on preclinical and clinical drug development and the selection and stratification of patients in clinical trials. These technologies, which are at varying stages of commercialization, include array-based comparative genomic hybridization, single-nucleotide polymorphism arrays, and (the most mature example) expression-based arrays. One of the rate-limiting steps in the routine clinical application of expression array-based technology is the need for suitable clinical samples. One of the major challenges moving forward, therefore, relates to the ability to use formalin-fixed, paraffin-embedded--derived tissue in expression profiling-based approaches.

UK publicly funded Clinical Trials Units supported a controlled access approach to share individual participant data but highlighted concerns

OBJECTIVES: Evaluate current data sharing activities of UK publicly funded Clinical Trial Units (CTUs) and identify good practices and barriers.

STUDY DESIGN AND SETTING: Web-based survey of Directors of 45 UK Clinical Research Collaboration (UKCRC)-registered CTUs.

RESULTS: Twenty-three (51%) CTUs responded: Five (22%) of these had an established data sharing policy and eight (35%) specifically requested consent to use patient data beyond the scope of the original trial. Fifteen (65%) CTUs had received requests for data, and seven (30%) had made external requests for data in the previous 12 months. CTUs supported the need for increased data sharing activities although concerns were raised about patient identification, misuse of data, and financial burden. Custodianship of clinical trial data and requirements for a CTU to align its policy to their parent institutes were also raised. No CTUs supported the use of an open access model for data sharing.

CONCLUSION: There is support within the publicly funded UKCRC-registered CTUs for data sharing, but many perceived barriers remain. CTUs are currently using a variety of approaches and procedures for sharing data. This survey has informed further work, including development of guidance for publicly funded CTUs, to promote good practice and facilitate data sharing.

Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling:results of a GITMO/EBMT randomized trial

A randomized trial was carried out comparing cyclosporin A (CsA) and short-term methotrexate (MTX) versus CsA alone for graft versus host disease (GVHD) prophylaxis in patients with severe aplastic anemia (SAA) undergoing allogeneic bone marrow transplantation (BMT) from a compatible sibling. Seventy-one patients (median age, 19 years; range, 4-46 years) were randomized to receive either CsA and MTX or CsA alone for the first 3 weeks after BMT. Subsequently, both groups received CsA orally, with gradual drug reduction until discontinuation 8 to 12 months after BMT. Patients randomized in both arms had comparable characteristics and received the same preparative regimen (ie, cyclophosphamide 200 mg/kg over 4 days). The median time for neutrophil engraftment was 17 days (range, 11-31 days) and 12 days (range, 4-45 days) for patients in the CsA/MTX group and the CsA alone group, respectively (P =.01). No significant difference was observed in the probability of either grade 2, grade 3, or grade 4 acute GVHD or chronic GVHD developing in the 2 groups. The Kaplan-Meier estimates of 1-year transplantation-related mortality rates for patients given either CsA/MTX or CsA alone were 3% and 15%, respectively (P =.07). With a median follow-up of 48 months from BMT, the 5-year survival probability is 94% for patients in the CsA/MTX group and 78% for those in the CsA alone group (P =. 05). These data indicate that the use of CsA with MTX is associated with improved survival in patients with SAA who receive transplants from compatible siblings. (Blood. 2000;96:1690-1697)

GTPase activity of dynamin and resulting conformation change are essential for endocytosis

Dynamin is a large GTPase with a relative molecular mass of 96,000 (Mr 96K) that is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Although its function is apparently essential for scission of newly formed vesicles from the plasma membrane, the nature of dynamin's role in the scission process is still unclear. It has been proposed that dynamin is a regulator (similar to classical G proteins) of downstream effectors. Here we report the analysis of several point mutants of dynamin's GTPase effector (GED) and GTPase domains. We show that oligomerization and GTP binding alone, by dynamin, are not sufficient for endocytosis in vivo. Rather, efficient GTP hydrolysis and an associated conformational change are also required. These data argue that dynamin has a mechanochemical function in vesicle scission.

Multiuser relaying over mixed RF/FSO links

A multiuser dual-hop relaying system over mixed radio frequency/free-space optical (RF/FSO) links is investigated. Specifically, the system consists of m single-antenna sources, a relay node equipped with n≥ m receive antennas and a single photo-aperture transmitter, and one destination equipped with a single photo-detector. RF links are used for the simultaneous data transmission from multiple sources to the relay. The relay operates under the decode-and-forward protocol and utilizes the popular V-BLAST technique by successively decoding each user's transmitted stream. Two common norm-based orderings are adopted, i.e., the streams are decoded in an ascending or a descending order. After V-BLAST, the relay retransmits the decoded information to the destination via a point-to-point FSO link in m consecutive timeslots. Analytical expressions for the end-to-end outage probability and average symbol error probability of each user are derived, while closed-form asymptotic expressions are also presented. Capitalizing on the derived results, some engineering insights are manifested, such as the coding and diversity gain of each user, the impact of the pointing error displacement on the FSO link and the V-BLAST ordering effectiveness at the relay.

Rapid, objective detection of cataract-induced blur using a bull's eye photodetector.

PURPOSE: To determine whether optical aberrations caused by cataract can be detected and quantified objectively using a newly described focus detection system (FDS). SETTING: The Wilmer Opthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. METHODS: The FDS uses a bull's eye photodetector to measure the double-pass blur produced from a point source of light. To determine the range and level of focus, signals are measured with a series of trial lenses in the light path selected to span the point of best focus to generate focus curves. The best corrected visual acuity (BCVA), refractive error, lens photograph grades, and FDS signals were obtained in 18 patients scheduled to have cataract surgery. The tests were repeated 6 weeks after surgery. RESULTS: The mean FDS outcome measures improved after cataract surgery, with increased peak height (P=.001) and decreased peak width (P=.001). Improvement in signal strength (integral of signal within +/-1.5 diopters of the point of best focus) strongly correlated with improvement in peak height (R(2)=.88, P<.0001) and photographic cataract grade (R(2)=.72, P<.0001). The mean BCVA improved from 20/50 to 20/26 (P<.0001). The improvement in BCVA correlated more closely with FDS signal strength (R(2)=.44, P=.001) than with cataract grade (R(2)=.25, P=.06). CONCLUSIONS: Improvement in FDS outcome measures correlated with cataract severity and improvement in visual acuity. This objective approach may be useful in long-term studies of cataract progression.