Synthesis of 1,3-diazepines and ring contraction to cyanopyrroles

Several tetrazolo[1,5-a] pyridines/2-azidopyridines undergo photochemical nitrogen elimination and ring expansion to 1,3-diazacyclohepta-1,2,4,6-tetraenes (7,10,13,16,19,22) as well as ring cleavage to cyanovinylketenimines (8,17,20b) in low temperature Ar matrices. 6,8-Dichlorotetrazolo[1,5-a] pyridine/2-azido-3,5-dichloropridine 6 undergoes ready exchange of the chlorine in position 8 (3) with ROH/RONa. 8-Chloro-6-trifluoromethyltetrazolo[1,5-a] pyridine 15 undergoes solvolysis of the CF3 group to afford 8-chloro-6-methoxycarbonyltetrazolo[1,5-a] pyridine 18. Several tetrazolopyridines/2-azidopyridines afford 1H- or 5H-1,3-diazepines in good yields on photolysis in the presence of alcohols or amines (11,14,23,25). 5-Chlorotetrazolo[1,5-a] pyridines/2-azido-6-chloropyridines 21 and 38 undergo a rearrangement to 1H- and 3H-3-cyanopyrroles 27 and 45, respectively. The mechanism of this rearrangement was investigated by N-15-labelling and takes place via transient 1,3-diazepines. The structures of 6,8-dichloro-tetrazolo[1,5-a] pyridine 6T, 6-chloro-8-ethoxytetrazolo[1,5-a] pyridine 9Tb, dipyrrolylmethane 28, and 2-isopropoxy-4-dimethylamino-5H-1,3-diazepine 25b were determined by X-ray crystallography. In the latter case, this represents the first reported X-ray crystal structure of a 5H-1,3-diazepine.

Whistleblower protection: Is Africa ready?

The article critically examines propositions driving the exportation of western whistleblower concepts into the developing world.(1) Specifically it attacks the prevailing view that public interest disclosure is somehow a culture-free, or at least a culture-muted phenomenon, governed by a set of rules and conventions detached from local histories and practices. The article concludes that this exportation is in the spirit of neo-colonialism and issues a note of warning about the dangers of dispersing western conceived forms of corruption reporting to Africa. Copyright (c) 2005 John Wiley & Sons, Ltd.

The use of email in a child and adolescent mental health service: are staff ready?

All staff members of a child and adolescent mental health service were invited to participate in a survey about the use of email. Sixty-two of the 105 staff members responded to the survey, a participation rate of 59%. Of the respondents, 32 were allied health staff, 10 were nurses, seven were administrative staff, six were medical staff, three were operational staff and four were acting in a combination of these roles. The respondents reported extensive work-related email usage and considered that they were confident in using email despite low levels of training. However, they did not feel that they understood the legal and ethical issues involved. Furthermore, there was limited incorporation of email into standard record keeping. The majority of respondents thought that increased use of email would lead to a greater workload, a consequence they considered would probably increase over time. Many commented on the quick and practical use of this medium, but were wary about using email with individuals outside the service organization, especially if it were to contain clinical material. There was low use of email directly with clients, and clinicians were ambivalent about incorporating email into therapy. The results suggest that it is timely to consider the utility and appropriateness of email communication with clients and external service providers, and to formulate guidelines and procedures to ensure the confidentiality of client information and the safety of clients and staff.

Relationships of activity and sugar drink intake on fat mass development in youths

Purpose: To determine whether a significant relationship exists between fat mass (FM) development and physical activity (PA) and/or sugar-sweetened drink (SD) consumption in healthy boys and girls aged 8-19 yr. Methods: A total of 105 males and 103 females were assessed during childhood and adolescence for a maximum of 7 yr and a median of 5 yr. Height was measured biannually. Fat-free mass (FFM) and FM were assessed annually by dual x-ray absorptiometry (DXA). PA was evaluated two to three times annually using the PAQ-C/A. Energy intake and SD were assessed using a 24-h dietary intake questionnaire also completed two to three times per year. Years from peak height velocity were used as a biological maturity age indicator. Multilevel random effects models were used to test the relationship. Results: When controlling for maturation, FFM, and energy intake adjusted for SD, PA level was negatively related to FM development in males (P < 0.05) but not in females (P > 0.05). In contrast, there was no relationship between SD and FM development of males or females (P > 0.05). There was also no interaction effect between SD and PA (P > 0.05) with FM development. Conclusion: This finding tends support to the idea that increasing PA in male youths aids in the control of FM development. Models employed showed no relationship between SD and FM in either gender.

Measurement of strain and strain rate by echocardiography - Ready for prime time?

Strain and strain rate (SR) are measures of deformation that are basic descriptors of both the nature and the function of cardiac tissue. These properties may now be measured using either Doppler or two-dimensional ultrasound techniques. Although these measurements are feasible in routine clinical echocardiography, their acquisition and analysis nonetheless presents a number of technical challenges and complexities. Echocardiographic strain and SR imaging has been applied to the assessment of resting ventricular function, the assessment of myocardial viability using low-dose dobutamine infusion, and stress testing for ischemia. Resting function assessment has been applied in both the left and the fight ventricles, and may prove particularly valuable for identifying myocardial diseases and following up the treatment response. Although the evidence base is limited, SR imaging seems to be feasible and effective for the assessment of myocardial viability. The use of the technique for the detection of ischemia during stress echocardiography is technically challenging and likely to evolve further. The clinical availability of strain and SR measurement may offer a solution to the ongoing need for quantification of regional and global cardiac function. Nonetheless, these techniques are susceptible to artifact, and further technical development is necessary.

General practice in Australia 2020: "robust and ready" or "rudderless and reeling"?

The future role and structure of Australian general practice remains uncertain, despite a decade of seemingly constant change following the release of the National Health Strategy papers. Some of the suggested change strategies (such as rural Practice Incentive Payments and practice accreditation) have been implemented; others (such as general practitioner involvement with area health authorities in delivering national goals and targets for communities) still await attention. An overarching vision for our health care system in 2020 and general practice's role within it are still to be clearly enunciated. Australia is at variance with other Western countries, such as the United Kingdom, Canada and New Zealand, which have spent significant time refocusing their health systems to deal with an ageing population with an increased burden of chronic disease. Health bureaucrats and governments need to invest strategically in operational primary care now. This will require the active commitment of general practice's national bodies to articulate and actively promote a shared vision for Australian general practice.

The finance of biotechnology:investment in new biotechnology firms by British venture capitalists-attitudes to, and evaluation of, business proposals

A notable feature of the recent commercialisation of biotechnology has been the success of 200 or so new firms, established in America since 1976, in exploiting specialised market niches. A key factor in their formation has been the ready availability of venture capital funding. These firms have been instrumental in establishing America's lead in exploiting biotechnology. It is this example which Britain has attempted to emulate as part of its strategy for developing its own biotechnology capabilities. This thesis investigated some aspects of the relationship between biotechnology and venture capital, concentrating on the determinants of the venture capitalist's investment decision. Following an extensive literature survey, two hypothetical business proposals were used to find what venture capitalists themselves consider to be the key elements of this decision. It was found that venture capitalists invest in people, not products, and businesses, not industries. It was concluded that venture capital-backed small firms should, therefore, be seen as an adjunct to the development of biotechnology in Britain, rather than as a substitute for a co-ordinated, co-operative strategy involving Government, the financial institutions, industry and academia. This is chiefly because the small size of the UK's domestic market means that many potentially important innovations in biotechnology may continue to be lost, since the short term identification of market opportunities for biotechnology products will dictate that they are insupportable in Britain alone. In addition, the data analysis highlighted some interesting methodological issues concerning the investigation of investment decision making. These related especially to shortcomings in the use of scoresheets and questionnaires in research in this area. The conclusion here was that future research should concentrate on the reasons why an individual reaches an investment decision. It is argued that only in this way can the nature of the evaluation procedures employed by venture capitalists be properly understood.

Using the theory of planned behaviour to understand binge drinking:the importance of beliefs for developing interventions

Objectives. To elicit students' salient beliefs in relation to binge drinking, and to examine the extent to which individual salient beliefs predict theory of planned behaviour (TPB) constructs in relation to binge drink, and actual drinking behaviour assessed later that evening. Design. Longitudinal, over a single evening. Methods. 192 students were recruited as they entered a campus bar at the beginning of the evening. They completed questionnaires with open-ended questions eliciting beliefs concerning binge drinking, and ratings scales assessing standard TPB constructs in relation to binge drinking. At the end of the evening, 181 completed a second questionnaire and recorded the number of alcoholic drinks they had consumed. Results. Beliefs were reliably coded (all kappas =0.79). Students with higher intentions to binge drink were more likely to believe that their friends approved of binge drinking, and that (lack of) money would make it difficult. Students who reported drinking more alcohol at the end of the evening were more likely to believe that getting drunk is an advantage/what they would like about binge drinking tonight, that their sports teams would approve, and that celebrating, drinking patterns, and environment would make it easy to binge drink. Conclusions. The present study has identified the individually salient beliefs relating to drinking behaviour that the TPB states should be addressed by interventions to alter behaviour, and which that should be assessed as mediators in intervention research. As a whole, these findings highlight the importance of perceived peer norms in binge drinking in this population, and support the idea of interventions to challenge the perception of social pressure to binge drink. ©2011 The British Psychological Society.

Linked data for the 21st Century enterprise:from silos to supply chains

Six actions for collation collective intelligence to inform and accelerate change

Investigating the delivery of antimicrobial proteins and aminoglycoside antibiotics to the airways

Biopharmaceuticals are finding wide applications in the management of diverse disease conditions. Pulmonary delivery of proteins may constitute an effective and efficient non-invasive alternative to parenteral delivery, which is currently the main route of administration of biopharmaceutical drugs. A particular area, in which pulmonary delivery of peptides and proteins may find ready application, is in the local delivery of antimicrobial peptides and proteins to the airway, a measure that could potentially bring about improvements to currently available antipseudomonal therapies. This thesis has therefore sought to develop inhalable antimicrobial proteins in combination with antibiotics that have particularly good antimicrobial activity against Pseudomonas aeruginosa infections in the respiratory tract of people with cystic fibrosis (CF). Through process optimisation, a suitable spray drying method was developed and used for the preparation of active, inhalable dry powder formulations of the antimicrobial protein, lactoferrin, and aminoglycosides (tobramycin and gentamicin). The physicochemical properties, aerosolisation performance and the antibacterial properties of the various spray-dried formulations were assessed. In addition, a relevant in vitro cellular model was employed to investigate the potential cytotoxic and pro-inflammatory effects of the various formulations on four bronchial human epithelial cells together with their effectiveness at reducing bacterial colonies when administered on to biofilm co-cultured on the epithelial cells. It was found that following spray drying the particles obtained were mostly spherical, amorphous and possessed suitable aerosolisation characteristics. The various spray-dried antimicrobial proteins (lactoferrin or apo lactoferrin) and co-spray dried combinations of the proteins and aminoglycosides were found to exhibit bactericidal activity against planktonic and biofilms of P. aeruginosa. In general, the spray drying process was found not to significantly affect the antimicrobial activities of the protein. Treatment of the different bronchial epithelial cell lines with the antimicrobial formulations showed that the various formulations were non-toxic and that the co-spray dried combinations significantly reduced established P. aeruginosa biofilms on the four bronchial epithelial cells. Overall, the results from this thesis demonstrates that spray drying could potentially be employed to prepare inhalable antimicrobial agents comprised of proteins and antibiotics. These new combinations of proteins and aminoglycosides has promising applications in the management of P. aeruginosa in the airway of cystic fibrosis patients.

A pilot study to evaluate the self-medication system for liver transplant patients at the Queen Elizabeth Hospital in Birmingham

Background and Objective: Medication non-compliance is a considerable obstacle in achievinga therapeutic goal, whichcan result in poorerhealthcare outcomes, increased expenditure, wastage and potential for medication resistance. The UK Government’s Audit Commission’s publication ‘A Spoonful of Sugar’1 addresses these issues and promotes self-medication systems as a possible solution. The self-medication system within the Liver Transplant Unit (LTU) was implemented to induct patients onto new post- transplantation medication regimes ready for discharge. The system involves initial consultations with both the Liver Transplant Pharmacist and Trans- plant Co-ordinator, supported with additional advice as and when necessary. Design: Following ethical approval, evaluation of the self-medication sys- tem for liver transplant patients was conducted between January and March 2004 via two methods: audit and structured post-transplantation interview. The audit enabled any discrepancies between current Hospital guidelines and Liver Transplant Unit (LTU) practices to be highlighted. Patient interviews generated a retrospective insight into patient acceptance of the self-medication system. Setting: LTU, Queen Elizabeth Hospital, Birmingham, England. Main Outcome Measures: LTU compliance with Hospital self-medication guidelines and patient insight into self-medication system. Results: A total of seven patients were audited. Findings illustrated that self- medication by transplant patients is a complex process which was not fully addressed by current Hospital self-medication guidelines. Twenty-three patients were interviewed, showing an overwhelming positive attitude to- wards participating in their own care and a high level of understanding towards their individual medication regimes. Following a drugs counselling session, 100% of patients understood why they were taking their medica- tion, and their doses, 95% understood how to take their medication and 85% were aware of potential side effects. Conclusions: From this pilot evaluation it can be stated that the LTU self-medication system is appreciated by patients and assists them in fully understanding their medication regimes. There appear to be no major defects in the system. However areas such as communication barriers and on-going internet education were illustrated as areas for possible future investigation. References: 1. Audit Commission. A spoonful of sugar – medicines management in NHS hospitals. London: Audit Commission; 2001.

Drinking while thirsty can lead to conditioned increases in consumption

A within-subject design was used to test whether repeatedly drinking a novel-flavoured and coloured drink while thirsty would influence subsequent liking for or consumption of that drink, compared to a different flavoured and coloured drink repeatedly consumed while less thirsty. Each participant was given 300 ml of one flavoured drink (H) after consuming a high salt meal (5.27 g of salt), and 300 ml of another flavoured drink (L) after consuming a low salt meal (1.27 g of salt). Participants had 4 sessions with each meal-type/drink combination, in an intermixed order. Pre- and post-training assessments of the drinks were conducted to determine the impact of the training regime on pleasantness and perceived thirst-quenching effect of the drinks. The final session included a choice test, and ad libitum access to the chosen drink, after either a high or low salt meal. In this final choice session, people drank almost twice as much H as L; however, there were no differential effects of past training on rated liking or choice. The increased consumption of H might reflect greater liking for H which was not detected by the rating scales; or it might reflect the learning of greater "conditioned thirst" in response to the flavour of H. © 2002 Elsevier Science Ltd. All rights reserved.

Public libraries and the right to the [smart] city

The future of public libraries has been threatened by funding cuts and new digital technologies which have led many people to question their traditional role and purpose. However, freedom of information, ready access to knowledge and information literacy in all its digital and analog guises are more important than ever. Thus, public libraries remain significant spaces and places where people can socially interact and learn. In many countries public libraries are reinventing themselves and part of this process has been the redesign of library services and the design and construction of new library building and facilities that articulate the values, purpose and role of what has been termed 'the next library'. Following discussion of new library developments in London, Birmingham and Worcester in the UK, Aarhus in Denmark and Helsinki in Finland, the article concludes that public libraries are now both social and media spaces as well as being important physical places that can help city dwellers decide what type of urban world they want to see.

Development of a digital tool to overcome the challenges of rural food SMEs

It has been recognised that throughout the UK, rural economies have a significant potential for growth but despite the potential for growth, many rural businesses face barriers that prohibit their expansion. In this study, we focus on one particular group of rural small- to medium-sized enterprises (SMEs): food and drink producers. Through user engagement activities, we identify the issues and needs associated with distributing products to the market, in order to understand the main issues which prevent rural food and drink SMEs from expansion, and to establish the requirements for a digital solution to this challenge.

Factors affecting emergency department length of stay of patients admitted to telemetry and critical care units

The purpose of this study was to determine the emergency department (ED) length of stay (LOS) of patients admitted to inpatient telemetry and critical care units and to identify the factors that contribute to a prolonged ED LOS. It also examined whether there was a difference in ED LOS between clients evaluated by an ED physician, an Advanced Registered Nurse Practitioner (ARNP) or a Physician's Assistant (PA).^ A data collection tool was devised and used to record data obtained by retrospectively reviewing 110 charts of patients from this sample. The mean ED LOS was 286.75 minutes. Multiple factors were recorded as affecting the ED LOS of this sample, including: age, diagnosis, consultations, multiple radiographs, pending admission orders, nurse unable to call report/busy, relatives at bedside, observation or stabilization necessary, bed not ready and infusion in progress. No significant difference in ED LOS was noted between subjects initially evaluated by a physician, an ARNP or a PA. ^