CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts

Objective: To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. Methods: CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Results: Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Conclusions: Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death. Copyright © 2011 Lippincott Williams & Wilkins

Minimal residual disease detection with tumor-specific CD160 correlates with event-free survival in chronic lymphocytic leukemia

In chronic lymphocytic leukemia (CLL), the detection of minimal residual disease (MRD) correlates with outcome in the trial setting. However, MRD assessment does not guide routine clinical management and its assessment remains complex. We incorporated detection of the B cell, tumor-specific antigen CD160 to develop a single-tube, flow cytometry assay (CD160FCA) for CLL MRD to a threshold of 10(−4) to 10(−5). One hundred and eighty-seven patients treated for CLL were enrolled. Utilizing the CD160FCA methodology, there was a high level of comparison between blood and bone marrow (R=0.87, P<0.001). In a validation cohort, CD160FCA and the international standardised approach of the European Research Initiative on CLL group demonstrated high concordance (R=0.91, P<0.01). Patients in complete remission (CR) and CD160FCA negative had longer event-free survival (EFS) (63 vs 16 months, P<0.01) and prolonged time to next treatment (60 vs 15 months, P<0.001) vs MRD positive patients; with a median time to MRD positivity of 36 months. In multivariate analysis, CD160FCA MRD detection was independently predictive of EFS in patients in CR and even predicted EFS in the good-risk cytogenetic subgroup. CD160FCA offers a simple assay for MRD detection in CLL and gives prognostic information across different CLL risk groups

Reducing Viral Load Measurements to Once a Year in Patients on Stable, Virologically Suppressive Cart Regimen: Findings from the Australian HIV Observational Database.

Reducing viral-load measurements to annual testing in virologically suppressed patients increases the estimated mean time those patients remain on a failing regimen by 6 months. This translates to an increase in the proportion of patients with at least one Thymidine Analogue Mutation from 10% to 32% over one year

Resolving structure of the disc around HD100546 at 7 mm with ATCA

There is much evidence that planet formation is occurring in the disc around the Herbig Be star HD100546. To learn more about the processes occurring in this disc, we conducted high-resolution imaging at 43/45 GHz with the Australia Telescope Compact Array. Multiple array configurations were used, providing a best spatial resolution of ∼0.15 arcsec, or 15 au at HD100546's distance of ∼100 pc. Significant structure is revealed, but its precise form is dependent on the u − v plane sampling used for the image reconstruction. At a resolution of ≤30 au, we detected an inner gap in the disc with a radius of ∼25 au and a position angle approximately along the known disc major axis. With different weighting, and an achieved resolution of ∼15 au, emission appears at the centre and the disc takes on the shape of an incomplete ring, much like a horseshoe, again with a gap radius of ∼25 au. The position angle of the disc major axis and its inclination from face-on are determined to be 140° ± 5° and 40° ± 5°, respectively. The ∼25 au gap radius is confirmed by a null in the real part of the binned visibilities at 320 ± 10 kλ, whilst the non-axisymmetric nature is also confirmed through significant structure in the imaginary component. The emission mechanism at the central peak is most likely to be free–free emission from a stellar or disc wind. Overall our data support the picture of at least one, but probably several, giant planets orbiting HD100546 within 25 au

Household Tobacco Smoke and Admission Weight Predict Severe Bronchiolitis in Infants Independent of Deprivation: Prospective Cohort Study

To examine demographic, environmental and clinical factors associated with severe bronchiolitis in infants admitted to hospital and quantify the independent effects of these factors

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

Problem-solving training: assessing the feasibility and acceptability of delivering and evaluating a problem-solving training model for front-line prison staff and prisoners who self-harm

Objectives: Problem-solving skills training is adaptable, inexpensive and simple to deliver. However, its application with prisoners who self-harm is unknown. The study assessed the feasibility and acceptability of a problem-solving training (PST) intervention for prison staff and prisoners who self-harm, to inform the design of a large-scale study. Design and setting: A mixed-methods design used routinely collected data, individual outcome measures, an economic protocol and qualitative interviews at four prisons in Yorkshire and Humber, UK. Participants: (i) Front-line prison staff, (ii) male and female prisoners with an episode of self-harm in the previous 2 weeks. Intervention: The intervention comprised a 1 hour staff training session and a 30 min prisoner session using adapted workbooks and case studies. Outcomes: We assessed the study processes—coverage of training; recruitment and retention rates and adequacy of intervention delivery—and available data (completeness of outcome data, integrity of routinely collected data and access to the National Health Service (NHS) resource information). Prisoner outcomes assessed incidence of self-harm, quality of life and depression at baseline and at follow-up. Qualitative findings are presented elsewhere. Results: Recruitment was higher than anticipated for staff n=280, but lower for prisoners, n=48. Retention was good with 43/48 (89%) prisoners completing the intervention, at follow-up we collected individual outcome data for 34/48 (71%) of prisoners. Access to routinely collected data was inconsistent. Prisoners were frequent users of NHS healthcare. The additional cost of training and intervention delivery was deemed minimal in comparison to ‘treatment as usual’. Outcome measures of self-harm, quality of life and depression were found to be acceptable. Conclusions: The intervention proved feasible to adapt. Staff training was delivered but on the whole it was not deemed feasible for staff to deliver the intervention. A large-scale study is warranted, but modifications to the implementation of the intervention are required