Dual roles for potassium hydride in haloarene reduction : CSNAr and SET reduction via organic electron donors formed in benzene

Potassium hydride behaves uniquely and differently than sodium hydride towards aryl halides. Its reactions with a range of haloarenes, including designed 2,6-dialkylhaloarenes, were studied in THF and in benzene. In THF, evidence supports concerted nucleophilic aromatic substitution, CSNAr, and the mechanism originally proposed by Pierre et al. is now validated through DFT studies. In benzene, besides this pathway, strong evidence for single electron transfer chemistry is reported. Experimental observations and DFT studies lead us to propose organic super electron donor generation to initiate BHAS (base-promoted homolytic aromatic substitution) cycles. Organic donor formation originates from deprotonation of benzene by KH; attack on benzene by the resulting phenylpotassium generates phenylcyclohexadienylpotassium that can undergo (i) deprotonation to form an organic super electron donor or (ii) hydride loss to afford biphenyl. Until now, BHAS reactions have been triggered by reaction of a base, MOtBu (M = K, Na), with many different types of organic additive, all containing heteroatoms (N or O or S) that enhance their acidity and place them within range of MOtBu as a base. This paper shows that with the stronger base, KH, even a hydrocarbon (benzene) can be converted into an electron-donating initiator

ELCID: early lung cancer identification and diagnosis - an embedded interview study to explore patient participation and recruitment

Background The ELCID Trial is a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of giving an urgent chest x-ray to smokers, and recent exsmokers, aged over 60 with new chest symptoms. Aims The qualitative component explores the feasibility of individually randomising patients to an urgent CXR or not and investigates any barriers to patient participation. Methods To date we have conducted semi-structured interviews with six primary care staff (practice managers, research nurses), ten patients randomised to ‘extra-NICE’ guidelines for referral for urgent chest x-ray, and six patients randomised to ‘usual care’ (NICE guidelines)). We hope to also interview patients who decline randomisation. Interviews were analysed using a Framework approach. Results Initial analysis indicated that practices have struggled to recruit patients, partly due to the eligibility criteria that requires ex-smokers to have stopped smoking within the last five years. Practices with a research nurse have recruited the most patients. Patients indicated that they are happy to take part in the trial and their anxiety levels were not raised. Most patients hoped to be randomised to urgent chest x-ray, although those who were not did not go back to their GP to request one. Conclusions Eligibility criteria needed revision to include ex-smokers of any duration. These preliminary findings suggest that the trial appears to be feasible and patients are happy to accept randomisation. The findings will inform the design of the main trial in the future

Immediate chest X-ray for patients at risk of lung cancer presenting in primary care: randomised controlled feasibility trial

Background: Achieving earlier stage diagnosis is one option for improving lung cancer outcomes in the United Kingdom. Patients with lung cancer typically present with symptoms to general practitioners several times before referral or investigation. Methods: We undertook a mixed methods feasibility individually randomised controlled trial (the ELCID trial) to assess the feasibility and inform the design of a definitive, fully powered, UK-wide, Phase III trial of lowering the threshold for urgent investigation of suspected lung cancer. Patients over 60, with a smoking history, presenting with new chest symptoms to primary care, were eligible to be randomised to intervention (urgent chest X-ray) or usual care. Results: The trial design and materials were acceptable to GPs and patients. We randomised 255 patients from 22 practices, although the proportion of eligible patients who participated was lower than expected. Survey responses (89%), and the fidelity of the intervention (82% patients X-rayed within 3 weeks) were good. There was slightly higher anxiety and depression in the control arm in participants aged >75. Three patients (1.2%) were diagnosed with lung cancer. Conclusions: We have demonstrated the feasibility of individually randomising patients at higher risk of lung cancer, to a trial offering urgent investigation or usual care

Faktorer kring äldres måltidssituation och deras påverkan på lönsamhet : Innovativa lösningar genom offentlig upphandling

The purpose of this study was to examine how innovative solutions within public procurement concerning the elderly with aid decisions affect well-being and economic performance. Many decisions concerning human resources are taken without consideration for its economic effect. This means that measures to achieve improvement in this area are only seen as economic costs for organizations instead of investments since the positive effects on profitability is not calculated. To be able to predict the profitability of measures concerning human resources, there is a need to be able to measure the economic impact of these actions and then get a picture of the total costs of their implementation. In Söderhamns municipality, the distribution of food supplies to the elderly living at home in Trönö/Norrala was transferred to a private company. To measure the impact of this action empirical was data gathered from the municipality concerning current expenses and the nutritional status of the elderly. Interviews and own calculations were made in order to estimate costs that the municipality did not have in its own calculations. The results of this study showed a trend towards increased well-being of the elderly, which could mean a cost reduction in medical costs in the future. The private company that now handles the food distribution also hired more staff, which leads to increased tax revenue for the municipality. Even with these factors, the total cost of the new system is still higher than the old system. However, these factors do mean a lower total cost compared to previous cost estimates of the municipality for the new system. To get a more accurate picture of the total costs off this action more extensive calculations is required. However, this study is a step forward in how these kinds of actions can be measured financially in a way that sees more to how they affect society as a whole instead of just its affect in certain areas.Syftet med denna studie var undersöka hur innovativa lösningar inom offentlig upphandling gällande äldre med biståndsbeslut påverkar välmående och ekonomiskt resultat. Många beslut gällande mänskliga resurser tas utan några ekonomiska underlag. Detta gör att åtgärder för att nå förbättring inom detta endast räknas som ekonomiska kostnader istället för investeringar då eventuella positiva effekter på lönsamhet inte beräknas. För att kunna förutse lönsamheten av åtgärder gällande mänskliga resurser finns det ett behov av att kunna mäta ekonomisk påverkan från dessa och då få en bild av totala kostnader för åtgärden. I Söderhamns kommun har matförsörjningen till hemmaboende äldre i Trönö/Norrala överlåtits till ett privat företag. För att mäta effekten av detta samlades empirisk data från kommunen gällande kostnader och de äldres näringsstatus. Intervjuer och egna beräkningar har även utförts för att uppskatta kostnader som kommunen inte har med i sina kostnadsberäkningar. Resultatet av denna studie visade en trend mot ökat välmående hos de äldre, vilket kan innebära en kostnadsreduktion i medicinska kostnader i framtiden. Det tillsammans med ökade skatteintäkter på grund av att Tempo utökat sin personal innebär en lägre totalkostnad för det nya systemet jämfört med tidigare beräkningar av kommunen. För att få en mer precis kostnadsbild krävs det fler och mer omfattande beräkningar. Denna studie är dock ett steg på vägen i hur denna typ av åtgärder kan mätas ekonomiskt

‘Once I knew there was a choice, I wanted to exercise that choice': using qualitative methods to understand why patients decline surgical trials

The BOLERO trial (Bladder cancer: Open versus Lapararoscopic or RObotic cystectomy) is a pilot study to determine the feasibility of randomisation to open versus laparoscopic access cystectomy in patients with bladder cancer. We describe the results of an embedded qualitative sub-study which explored why patients decline randomisation. Methods: 10 semi structured interviews were undertaken with patients recruited from 3 sites in England. Data were analysed for key themes. Results: Most patients declined the trial because they had preferences for, and could choose, which surgical method they would be given- in most cases the robotic option. Patients described an intuitive ‘sense' that favoured the new technology and had carried out their own inquiries, including internet research and talking with previous patients and with friends and family with medical backgrounds. Medical histories and lifestyle considerations also shaped these personalised choices. Of importance too, however, were the messages patients perceived from their clinical encounters. Whilst some patients felt their surgeon favoured the robotic option, others interpreted ‘indirect' cues such as the ‘established' reputation of the surgeon and surgical method and comments made during pre-op assessments. Many patients expressed a wish for greater direction from their surgeon when making these decisions. Conclusion: Patients like to exercise informed choice over the type of surgery they receive. For trials where the ‘new technology' is routinely available to patients, there will likely be difficulties with recruitment. This questions the feasibility of similar trials in the future

Radiocarbon and linguistic dates for occupation of the South Wellesley Islands, Northern Australia

Radiocarbon dates from three Kaiadilt Aboriginal sites on the South Wellesley Islands, southern Gulf of Carpentaria, demonstrate occupation dating to c.1600 years ago. These results are at odds with published linguistic models for colonisation of the South Wellesley archipelago suggesting initial occupation in the last 1000 years, but are consonant with archaeological evidence for post-4200 BP occupation of islands across northern Australia, particularly in the last 2000 years

A feasibility study examining the effect on lung cancer diagnosis of offering a chest X-ray to higher-risk patients with chest symptoms: protocol for a randomized controlled trial

Background In order to improve lung cancer survival in the UK, a greater proportion of resectable cancers must be diagnosed. It is likely that resectability rates would be increased by more timely diagnosis. Aside from screening, the only way of achieving this is to reduce the time to diagnosis in symptomatic cancers. Currently, lung cancers are mainly diagnosed by general practitioners (GPs) using the National Institute for Health and Clinical Excellence (NICE) guidelines for urgent referral for chest X-ray, which recommend urgent imaging or referral for patients who have one of a number of chest symptoms for more than 3 weeks. We are proposing to expand this recommendation to include one of a number of chest symptoms of any duration in higher-risk patients. Methods/Design We intend to conduct a trial of imaging in these higher-risk patients and compare it with NICE guidelines to see if imaging improves stage at diagnosis and resection rates. This trial would have to be large (and consequently resource-intensive) because most of these patients will not have lung cancer, making optimal design crucial. We are therefore conducting a pilot trial that will ascertain the feasibility of running a full trial and provide key information that will be required in order to design the full trial. Discussion This trial will assess the feasibility and inform the design of a large, UK-wide, clinical trial of a change to the NICE guidelines for urgent referral for chest X-ray for suspected lung cancer. It utilizes a combination of workshop, health economic, quality of life, qualitative, and quantitative methods in order to fully assess feasibility.</p

ELCID: early lung cancer identification and diagnosis - an embedded interview study to explore patient participation and recruitment

Background: the ELCID Trial is a feasibility randomised controlled trial examining the effect on lung cancer diagnosis of giving an urgent chest x-ray to smokers, and recent ex-smokers, aged over 60 with new chest symptoms.Aims: the qualitative component explores the feasibility of individually randomising patients to an urgent CXR or not and investigates any barriers to patient participation.Methods: to date we have conducted semi-structured interviews with six primary care staff (practice managers, research nurses), ten patients randomised to ‘extra-NICE' guidelines for referral for urgent chest x-ray, and six patients randomised to ‘usual care' (NICE guidelines)). We hope to also interview patients who decline randomisation. Interviews were analysed using a Framework approach.Results: initial analysis indicated that practices have struggled to recruit patients, partly due to the eligibility criteria that requires ex-smokers to have stopped smoking within the last five years. Practices with a research nurse have recruited the most patients. Patients indicated that they are happy to take part in the trial and their anxiety levels were not raised. Most patients hoped to be randomised to urgent chest x-ray, although those who were not did not go back to their GP to request one.Conclusions: eligibility criteria needed revision to include ex-smokers of any duration. These preliminary findings suggest that the trial appears to be feasible and patients are happy to accept randomisation. The findings will inform the design of the main trial in the future