Users’ experiences of lighting controls: a case-study

The aim of this paper is to elucidate how occupants perceive their lit environments in a university setting and how they interact with lighting controls using qualitative methods. Semi-structured interviews were carried out with academic teaching and research staff. Thematic analysis identified four main themes: control and choice, connection with the outdoors, concentration, and comfort. Participants were largely able to control and adapt their lighting using small power lighting in office spaces and they perceived this as beneficial to comfort and concentration. Participants expressed frustration with the light switches in classrooms, a lack of consistency in lighting controls across the university buildings was particularly notable. Installers should consider how piecemeal upgrades on large estates affect the perception of buildings where occupiers face multiple control systems. The management of the lighting in classroom spaces including the type and location of blinds, lack of regular window cleaning in some buildings and difficulty in minimising light on projection screens in upgraded classrooms were cited as areas for improvement. Wider implications for lighting control and management highlighted by this study include most notably that a lack of end users consultation has serious consequences on their perception of lighting upgrades and their willingness to employ “workarounds”

Mathematical modelling of cytokines, MMPs and fibronectin fragments in osteoarthritic cartilage

Osteoarthritis (OA) is a degenerative disease which causes pain and stiffness in joints. OA progresses through excessive degradation of joint cartilage, eventually leading to significant joint degeneration and loss of function. Cytokines, a group of cell signalling proteins, present in raised concentrations in OA joints, can be classified into pro-inflammatory and anti-inflammatory groups. They mediate cartilage degradation through several mechanisms, primarily the up-regulation of matrix metalloproteinases (MMPs), a group of collagen-degrading enzymes. In this paper we show that the interactions of cytokines within cartilage have a crucial role to play in OA progression and treatment. We develop a four-variable ordinary differential equation model for the interactions between pro- and anti-inflammatory cytokines, MMPs and fibronectin fragments (Fn-fs), a by-product of cartilage degradation and upregulator of cytokines. We show that the model has four classes of dynamic behaviour: homoeostasis, bistable inflammation, tristable inflammation and persistent inflammation. We show that positive and negative feedbacks controlling cytokine production rates can determine either a pre-disposition to OA or initiation of OA. Further, we show that manipulation of cytokine, MMP and Fn-fs levels can be used to treat OA, but we suggest that multiple treatment targets may be essential to halt or slow disease progression

The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine

The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10(8) RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 10(8) RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.The Pharmacogenomics Journal advance online publication, 3 January 2017; doi:10.1038/tpj.2016.87