Limits of 'patient-centredness'; valuing contextually specific communication patterns

Context Globally, doctor–patient communication is becoming synonymous with high-quality health care in the 21st century. However, what is meant by ‘good communication’ and whether there is consensus internationally remain unclear. Objectives Here, we characterise understandings of ‘good communication’ in future doctors from medical schools in three contextually contrasting continents. Given locally specific socio-cultural influences, we hypothesised that there would be a lack of global consensus on what constitutes ‘good communication’. Methods A standardised two-phase methodology was applied in turn to each of three medical schools in the UK, Egypt and India (n = 107 subjects), respectively, in which students were asked: ‘What is good communication?’ Phase I involved exploratory focus groups to define preliminary themes (mean number of participants per site: 17). Phase II involved thematic confirmation and expansion in one-to-one semi-structured interviews (mean number of participants per site: 18; mean hours of dialogue captured per site: 55). Findings were triangulated and analysed using grounded theory. Results The overarching theme that emerged from medical students was that ‘good communication’ requires adherence to certain ‘rules of communication’. A shared rule that doctors must communicate effectively despite perceived disempowerment emerged across all sites. However, contradictory culturally specific rules about communication were identified in relation to three major domains: family; gender, and emotional expression. Egyptian students perceived emotional aspects of Western doctors’ communication strikingly negatively, viewing these doctors as problematically cold and unresponsive. Conclusions Contradictory perceptions of ‘good communication’ in future doctors are found cross-continentally and may contribute to prevalent cultural misunderstandings in medicine. The lack of global consensus on what defines good communication challenges prescriptively taught Western ‘patient-centredness’ and questions assumptions about international transferability. Health care professionals must be educated openly about flexible, context-specific communication patterns so that they can avoid cultural incompetence and tailor behaviours in ways that optimise therapeutic outcomes wherever they work around the globe

Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

Prototype 1 MeV X -band linac for aviation cargo inspection

Aviation cargo unit load device (ULD) containers are typically much smaller than standard shipping containers, with a volume of around 1 m3. Standard 3-6 MeV x-ray screening linacs have too much energy to obtain sufficient contrast when inspecting ULDs, hence a lower 1 MeV linac is required. In order to obtain a small physical footprint, which can be adapted to mobile platform applications, a compact design is required, hence X-band radio-frequency technology is the ideal solution. A prototype 1.45 MeV linac cavity optimized for this application has been designed by Lancaster University and Science and Technology Facilities Council (STFC), manufactured by Comeb (Italy) and tested at Daresbury Laboratory using an e2v magnetron, modulator, and electron gun. The cavity is a bi-periodic π/2 structure, with beam-pipe aperture coupling to simplify the manufacture at the expense of shunt impedance, while keeping the transverse size as small as possible. The design, manufacture, and testing of this linac structure is presented. In order to optimize the image it is necessary to be able to modify the energy of the linac. It can be changed by altering the rf power from the magnetron but this also varies the magnetron frequency. By varying the beam current from 0-70 mA the beam energy varied from 1.45 to 1.2 MeV. This allows fast energy variation by altering the focus electrode bias voltage on the electron gun while keeping the dose rate constant by varying the repetition frequency. Varying the beam energy by varying the rf power and by varying the beam current are both studied experimentally. The momentum spread on the electron beam was between 1% and 5% depending on the beam current of 0-70 m

Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy

The epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma (SCC) of the head and neck. Most patients, however, do not respond or develop resistance to this agent. Mammalian target of rapamycin (mTOR) is involved in the pathogenesis of SCC of the head and neck (SCCHN). This study aimed to determine if targeting mTOR in combination with EGFR is effective in SCC, and to develop early pharmacodynamic markers of efficacy. Two SCC cell lines, one resistant (HEP2) and one of intermediate susceptibility (Detroit 562) to EGFR inhibitors, were xenografted in vivo and treated with an mTOR inhibitor (temsirolimus), an EGFR inhibitor (erlotinib) or a combination of both. Temsirolimus exerted superior growth arrest in both cell lines than erlotinib. The combined treatment resulted in synergistic antitumor effects in the Detroit 562 cell line. Immunohistochemical assessment of pharmacodynamic effects in fine-needle aspiration (FNA) biopsies early after treatment using phospho MAPK, Phospho-P70 and Ki67 as end points demonstrated pathway abrogation in the Detroit 562 tumours treated with the combination, the only group where regressions were seen. In conclusion, an mTOR inhibitor showed antitumor activity in EGFR-resistant SCC cell lines. Marked antitumor effects were associated with dual pathway inhibition, which were detected by early FNA biopsies

The conceptual design of CLARA, a novel fel test facility for ultra-short pulse generation

CLARA will be a novel FEL test facility focussed on the generation of ultra-short photon pulses with extreme levels of stability and synchronisation. The principal aim is to experimentally demonstrate that sub-cooperation length pulse generation with FELs is viable, and to compare the various schemes being championed. The results will translate directly to existing and future X-ray FELs, enabling them to generate attosecond pulses, thereby extending their science capabilities. This paper gives an overview of the motivation for CLARA, describes the facility design (reported in detail in the recently published Conceptual Design Report [1]) and proposed operating modes and summarises the proposed areas of FEL research

Regulatory (pan-)genome of an obligate intracellular pathogen in the PVC superphylum.

Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting >100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved