In silico identification of novel G protein coupled receptors

G-protein coupled receptors (GPCRs) are a superfamily of membrane integral proteins responsible for a large number of physiological functions. Approximately 50% of marketed drugs are targeted toward a GPCR. Despite showing a high degree of structural homology, there is a large variance in sequence within the GPCR superfamily which has lead to difficulties in identifying and classifying potential new GPCR proteins. Here the various computational techniques that can be used to characterize a novel GPCR protein are discussed, including both alignment-based and alignment-free approaches. In addition, the application of homology modeling to building the three-dimensional structures of GPCRs is described.

Putting policy initiatives into practice:adopting an “honest broker” approach to adapting small businesses against flooding

Purpose: Amidst the current economic climate, which places many constraints on expensive flood defence schemes, the policy makers tend to favour schemes that are sympathetic to the needs of small and medium-sized enterprises (SMEs) and which promote empowering local communities based on their individual local contexts. Research has shown that although several initiatives are in place to create behavioural change among SMEs in undertaking adaptation approaches against flooding, they often tend to delay their responses by means of a "wait and see" attitude. The paper aims to discuss these issues. Design/methodology/approach: This paper argues that unless there are conscious efforts in the policy-making community to undertake explicit measures to engage with SMEs in a collaborative way, the uptake of adaptation measures will not be achieved as intended. With the use of the "honest broker" approach the paper provides a conceptual way forward of how a sense of collaboration can be instigated in an engagement process between the policy makers and SMEs, so that the scientific knowledge is translated in an appropriately rational way, which best meets the expectations of the SMEs. Findings: The paper proposes a conceptual model for engaging SMEs that will potentially increase the uptake of flood adaptation measures by SMEs. This could be a useful model with which to kick start a collaborative engagement process that could escalate to wider participation in other areas to improve impact of policy initiatives. Originality/value: The paper lays the conceptual foundation for a new theoretical base in the area, which will encourage more empirical investigations that will potentially enhance the practicality of some of the existing policies. © Emerald Group Publishing Limited.

Representation and misrepresentation of scientific evidence in contemporary tobacco regulation:a review of tobacco industry submissions to the UK Government consultation on standardised packaging

BACKGROUND: Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. METHODS AND FINDINGS: We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. CONCLUSIONS: The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation, particularly stakeholder consultation, provide an opportunity for highly resourced corporations to slow, weaken, or prevent public health policies.

A critical evaluation of the volume, relevance and quality of evidence submitted by the tobacco industry to oppose standardised packaging of tobacco products

OBJECTIVES: To examine the volume, relevance and quality of transnational tobacco corporations' (TTCs) evidence that standardised packaging of tobacco products 'won't work', following the UK government's decision to 'wait and see' until further evidence is available. DESIGN: Content analysis. SETTING: We analysed the evidence cited in submissions by the UK's four largest TTCs to the UK Department of Health consultation on standardised packaging in 2012. OUTCOME MEASURES: The volume, relevance (subject matter) and quality (as measured by independence from industry and peer-review) of evidence cited by TTCs was compared with evidence from a systematic review of standardised packaging . Fisher's exact test was used to assess differences in the quality of TTC and systematic review evidence. 100% of the data were second-coded to validate the findings: 94.7% intercoder reliability; all differences were resolved. RESULTS: 77/143 pieces of TTC-cited evidence were used to promote their claim that standardised packaging 'won't work'. Of these, just 17/77 addressed standardised packaging: 14 were industry connected and none were published in peer-reviewed journals. Comparison of TTC and systematic review evidence on standardised packaging showed that the industry evidence was of significantly lower quality in terms of tobacco industry connections and peer-review (p<0.0001). The most relevant TTC evidence (on standardised packaging or packaging generally, n=26) was of significantly lower quality (p<0.0001) than the least relevant (on other topics, n=51). Across the dataset, TTC-connected evidence was significantly less likely to be published in a peer-reviewed journal (p=0.0045). CONCLUSIONS: With few exceptions, evidence cited by TTCs to promote their claim that standardised packaging 'won't work' lacks either policy relevance or key indicators of quality. Policymakers could use these three criteria-subject matter, independence and peer-review status-to critically assess evidence submitted to them by corporate interests via Better Regulation processes.

Pharmacology and the safe prescribing of drugs

Understanding the pharmacological principles and safe use of drugs is just as important in surgical practice as in any other medical specialty. With an ageing population with often multiple comorbidities and medications, as well as an expanding list of new pharmacological treatments, it is important that surgeons understand the implications of therapeutic drugs on their daily practice. The increasing emphasis on high quality and safe patient care demands that doctors are aware of preventable adverse drug reactions (ADRs) and interactions, try to minimize the potential for medication errors, and consider the benefits and harms of medicines in their patients. This chapter examines these aspects from the view of surgical practice and expands on the implications of some of the most common medical conditions and drug classes in the perioperative period. The therapeutic care of surgical patients is obvious in many circumstances – for example, antibacterial prophylaxis, thromboprophylaxis, and postoperative analgesia. However, the careful examination of other drug therapies is often critical not only to the sustained treatment of the associated medical conditions but to the perioperative outcomes of patients undergoing surgery. The benefit–harm balance of many therapies may be fundamentally altered by the stress of an operation in one direction or the other; this is not a decision that should wait until the anaesthetist arrives for a preoperative assessment or one that should be left to junior medical or nursing staff on the ward.

Better queue management in a busy public hospital of a developing country without appointment system::an application using data envelopment analysis

Queuing is a key efficiency criterion in any service industry, including Healthcare. Almost all queue management studies are dedicated to improving an existing Appointment System. In developing countries such as Pakistan, there are no Appointment Systems for outpatients, resulting in excessive wait times. Additionally, excessive overloading, limited resources and cumbersome procedures lead to over-whelming queues. Despite numerous Healthcare applications, Data Envelopment Analysis (DEA) has not been applied for queue assessment. The current study aims to extend DEA modelling and demonstrate its usefulness by evaluating the queue system of a busy public hospital in a developing country, Pakistan, where all outpatients are walk-in; along with construction of a dynamic framework dedicated towards the implementation of the model. The inadequate allocation of doctors/personnel was observed as the most critical issue for long queues. Hence, the Queuing-DEA model has been developed such that it determines the ‘required’ number of doctors/personnel. The results indicated that given extensive wait times or length of queue, or both, led to high target values for doctors/personnel. Hence, this crucial information allows the administrators to ensure optimal staff utilization and controlling the queue pre-emptively, minimizing wait times. The dynamic framework constructed, specifically targets practical implementation of the Queuing-DEA model in resource-poor public hospitals of developing countries such as Pakistan; to continuously monitor rapidly changing queue situation and display latest required personnel. Consequently, the wait times of subsequent patients can be minimized, along with dynamic staff scheduling in the absence of appointments. This dynamic framework has been designed in Excel, requiring minimal training and work for users and automatic update features, with complex technical aspects running in the background. The proposed model and the dynamic framework has the potential to be applied in similar public hospitals, even in other developing countries, where appointment systems for outpatients are non-existent.