Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.

BACKGROUND: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. METHODS: We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses). RESULTS: At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges. CONCLUSIONS: In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48

Emissions from village cookstoves in Haryana, India, and their potential impacts on air quality

Air quality in rural India is impacted by residential cooking and heating with biomass fuels. In this study, emissions of CO, CO2, and 76 volatile organic compounds (VOCs) and fine particulate matter (PM2.5) were quantified to better understand the relationship between cook fire emissions and ambient ozone and secondary organic aerosol (SOA) formation. Cooking was carried out by a local cook, and traditional dishes were prepared on locally built chulha or angithi cookstoves using brushwood or dung fuels. Cook fire emissions were collected throughout the cooking event in a Kynar bag (VOCs) and on polytetrafluoroethylene (PTFE) filters (PM2.5). Gas samples were transferred from a Kynar bag to previously evacuated stainless-steel canisters and analyzed using gas chromatography coupled to flame ionization, electron capture, and mass spectrometry detectors. VOC emission factors were calculated from the measured mixing ratios using the carbon-balance method, which assumes that all carbon in the fuel is converted to CO2, CO, VOCs, and PM2.5 when the fuel is burned. Filter samples were weighed to calculate PM2.5 emission factors. Dung fuels and angithi cookstoves resulted in significantly higher emissions of most VOCs (p &lt; 0.05). Utilizing dung-angithi cook fires resulted in twice as much of the measured VOCs compared to dung-chulha and 4 times as much as brushwood-chulha, with 84.0, 43.2, and 17.2g measured VOCkgg fuel carbon, respectively. This matches expectations, as the use of dung fuels and angithi cookstoves results in lower modified combustion efficiencies compared to brushwood fuels and chulha cookstoves. Alkynes and benzene were exceptions and had significantly higher emissions when cooking using a chulha as opposed to an angithi with dung fuel (for example, benzene emission factors were 3.18gkgg fuel carbon for dung-chulha and 2.38gkgg fuel carbon for dung-angithi). This study estimated that 3 times as much SOA and ozone in the maximum incremental reactivity (MIR) regime may be produced from dung-chulha as opposed to brushwood-chulha cook fires. Aromatic compounds dominated as SOA precursors from all types of cook fires, but benzene was responsible for the majority of SOA formation potential from all chulha cook fire VOCs, while substituted aromatics were more important for dung-angithi. Future studies should investigate benzene exposures from different stove and fuel combinations and model SOA formation from cook fire VOCs to verify public health and air quality impacts from cook fires

Play and metaphor in clinical supervision: keeping creativity alive

This article explores the use of play and metaphor in clinical supervision. The intention is not to attempt to cover the whole area of play, or the use of metaphor in clinical supervision, but rather to highlight particular aspects of their respective roles in the service of learning about therapeutic work. The relevance of the arts - especially the visual arts - in relation to this is also discussed. A number of brief clinical vignettes are included by way of illustration. All names, and some identifying details, have been changed to preserve confidentiality. (C) 2010 Elsevier Inc. All rights reserved

Managing knowledge transfer partnership for a rural community: the outcomes at Wirksworth, UK

Purpose – This paper aims to propose a knowledge transfer partnership (KTP) model, using higher education (HE) students researching in the UK. It is focused on community engagement via charitable trusts, New Opportunities Wirksworth (NOW) & Ecclesbourne Valley Rail (EVR). The researchers designed and implemented a pilot study that explored the potential of a small, yet attractive and active, market town to diversify and regenerate using tourism. This project, which has been funded by the UK Higher Education Innovation Fund (HEIF), has been devised to operate and monitor a KTP in the culturally important heritage market town of Wirksworth, in Derbyshire. Design/methodology/approach – A systems-thinking constructivist approach is used and employs problem-based learning (PBL) through engagement of students in research and data collection. The authors identified that skills for sustainable development within the community are dependent on the reintegration of complex, inter-dependent and inter-disciplinary factors. A holistic approach to the learning and knowledge shared within the community underpins UK initiatives to promote capacity development in ways to change knowledge applications across product and service boundaries. Therefore, in addition to encouraging diversification and regeneration through tourism, this project supported the University of Derby's academic agenda to promote experiential and entrepreneurial learning in students working at both undergraduate and postgraduate levels. This paper accords with the current university initiatives to meet the student employability agenda through the application of PBL and knowledge management. Findings – The creation of outcomes and recommendations for Wirksworth's stakeholders provides sustainability through the knowledge creation and sharing processes. There are seven outcomes that chart a path to development and knowledge transfer (KT) and sharing. The authors simultaneously provided an environment for students to gain skills and a community to acquire new knowledge, and these are the outcomes and output of this project. New learning styles may support inclusive academic practice (see related samples of PBL such as Ineson and Beresford in HLST resources 2001). Implications for building a KT community through the social capital accumulated in the project are explored. Originality/value – In taking PBL from the classroom to the community, the authors have created a new KT environment in which skills can be acquired and a regeneration strategy can be tested in a work-or-practice-related setting. Students recognise that they are building learning for themselves that is unique in that it cannot be recreated in a classroom setting. The authors see this project developing into a robust long-term partnership between communities and institutions with KT benefits to teaching staff in addition to students. These benefits will include new skills for PBL, working collaboratively with partners in the community to develop key skills in HE students, innovation in assessment, inclusive learning and teaching, experiential and entrepreneurial learning in practice

Molecular composition of particulate matter emissions from dung and brushwood burning household cookstoves in Haryana, India

Emissions of airborne particles from biomass burning are a significant source of black carbon (BC) and brown carbon (BrC) in rural areas of developing countries where biomass is the predominant energy source for cooking and heating. This study explores the molecular composition of organic aerosols from household cooking emissions with a focus on identifying fuel-specific compounds and BrC chromophores. Traditional meals were prepared by a local cook with dung and brushwood-fueled cookstoves in a village in Palwal district, Haryana, India. Cooking was done in a village kitchen while controlling for variables including stove type, fuel moisture, and meal. Fine particulate matter (PM2.5) emissions were collected on filters, and then analyzed via nanospray desorption electrospray ionization-high-resolution mass spectrometry (nano-DESI-HRMS) and high-performance liquid chromatography-photodiode array-high-resolution mass spectrometry (HPLC-PDA-HRMS) techniques. The nano-DESI-HRMS analysis provided an inventory of numerous compounds present in the particle phase. Although several compounds observed in this study have been previously characterized using gas chromatography methods a majority of the species in the nano-DESI spectra were newly observed biomass burning compounds. Both the stove (chulha or angithi) and the fuel (brushwood or dung) affected the composition of organic aerosols. The geometric mean of the PM2.5 emission factor and the observed molecular complexity increased in the following order: brushwood-chulha (7.3±1.8 g kg-1 dry fuel, 93 compounds), dung-chulha (21.1±4.2 g kg-1 dry fuel, 212 compounds), and dung-angithi (29.8±11.5 g kg-1 dry fuel, 262 compounds). The mass-normalized absorption coefficient (MACbulk) for the organic-solvent extractable material for brushwood PM2.5 was 3.7±1.5 and 1.9±0.8m2 g-1 at 360 and 405 nm, respectively, which was approximately a factor of two higher than that for dung PM2.5. The HPLC-PDA-HRMS analysis showed that, regardless of fuel type, the main chromophores were CxHyOz lignin fragments. The main chromophores accounting for the higher MACbulk values of brushwood PM2.5 were C8H10O3 (tentatively assigned to syringol), nitrophenols C8H9NO4, and C10H10O3 (tentatively assigned to methoxycinnamic acid)

Measurement of OH reactivity by laser flash photolysis coupled with laser-induced fluorescence spectroscopy

OH reactivity (k’OH) is the total pseudo-first-order loss rate coefficient describing the removal of OH radicals to all sinks in the atmosphere, and is the inverse of the chemical lifetime of OH. Measurements of ambient OH reactivity can be used to discover the extent to which measured OH sinks contribute to the total OH loss rate. Thus, OH reactivity measurements enable determination of the comprehensiveness of measurements used in models to predict air quality and ozone production, and, in conjunction with measurements of OH radical concentrations, to assess our understanding of OH production rates. In this work, we describe the design and characterisation of an instrument to measure OH reactivity using laser flash photolysis coupled to laser-induced fluorescence (LFP-LIF) spectroscopy. The LFP-LIF technique produces OH radicals in isolation, and thus minimises potential interferences in OH reactivity measurements owing to the reaction of HO2 with NO which can occur if HO2 is co-produced with OH in the instrument. Capabilities of the instrument for ambient OH reactivity measurements are illustrated by data collected during field campaigns in London, UK, and York, UK. The instrumental limit of detection for k’OH was determined to be 1.0 s-1 for the campaign in London and 0.4 s-1 for the campaign in York. The precision, determined by laboratory experiment, is typically < 1 s-1 for most ambient measurements of OH reactivity. Total uncertainty in ambient measurements of OH reactivity is ~6 %. We also present the coupling and characterisation of the LFP-LIF instrument to an atmospheric chamber for measurements of OH reactivity during simulated experiments, and provide suggestions for future improvements to OH reactivity LFP-LIF instruments