A review of the factors involved in older people's decision making with regard to influenza vaccination: a literature review

Aims and objectives. The aim of this paper was to develop an understanding of the factors involved in older people's decision making with regard to influenza vaccination to inform strategies to improve vaccine uptake and reduce morbidity and mortality. Background. Influenza is a major cause of morbidity and mortality world-wide. In the UK, it accounts for 3000–6000 deaths annually; 85% of these deaths are people aged 65 and over. Despite this, and the widespread and costly annual government campaigns, some older people at risk of influenza and the associated complications remain reluctant to take advantage of the offer of vaccination. Methods. A review of the English language literature referring to older people published between 1996 and 2005 was the method used. Inclusion and exclusion criteria were identified and applied. Results. The majority of the literature was quantitative in nature, investigating personal characteristics thought to be predictors of uptake, such as age, sex, co-morbidity, educational level, income and area of residence. However, there was little discussion of the possible reasons for the significance of these factors and conflict between findings was often evident, particularly between studies employing different methodologies. Other factors identified were prior experience, concerns about the vaccine, perceived risk and advice and information. Relevance to clinical practice. The wealth of demographic information available will be useful at a strategic level in targeting groups identified as being unlikely to accept vaccination. However, the promotion of person-centred ways of working that value the health beliefs, attitudes, perceptions and subjective experiences of older people is likely to be more successful during individual encounters designed to promote acceptance. Without more research in investigating these concepts, our understanding is inevitably limited

Nitric oxide and coronary vascular endothelium adaptations in hypertension

This review highlights a number of nitric oxide (NO)-related mechanisms that contribute to coronary vascular function and that are likely affected by hypertension and thus become important clinically as potential considerations in prevention, diagnosis, and treatment of coronary complications of hypertension. Coronary vascular resistance is elevated in hypertension in part due to impaired endothelium-dependent function of coronary arteries. Several lines of evidence suggest that other NO synthase isoforms and dilators other than NO may compensate for impairments in endothelial NO synthase (eNOS) to protect coronary artery function, and that NO-dependent function of coronary blood vessels depends on the position of the vessel in the vascular tree. Adaptations in NOS isoforms in the coronary circulation to hypertension are not well described so the compensatory relationship between these and eNOS in hypertensive vessels is not clear. It is important to understand potential functional consequences of these adaptations as they will impact the efficacy of treatments designed to control hypertension and coronary vascular disease. Polymorphisms of the eNOS gene result in significant associations with incidence of hypertension, although mechanistic details linking the polymorphisms with alterations in coronary vasomotor responses and adaptations to hypertension are not established. This understanding should be developed in order to better predict those individuals at the highest risk for coronary vascular complications of hypertension. Greater endothelium-dependent dilation observed in female coronary arteries is likely related to endothelial Ca2+ control and eNOS expression and activity. In hypertension models, the coronary vasculature has not been studied extensively to establish mechanisms for sex differences in NO-dependent function. Genomic and nongenomic effects of estrogen on eNOS and direct and indirect antioxidant activities of estrogen are discussed as potential mechanisms of interest in coronary circulation that could have implications for sex- and estrogen status-dependent therapy for hypertension and coronary dysfunction. The current review identifies some important basic knowledge gaps and speculates on the potential clinical relevance of hypertension adaptations in factors regulating coronary NO function

The adaptive buffered force QM/MM method in the CP2K and AMBER software packages.

The implementation and validation of the adaptive buffered force (AdBF) quantum-mechanics/molecular-mechanics (QM/MM) method in two popular packages, CP2K and AMBER are presented. The implementations build on the existing QM/MM functionality in each code, extending it to allow for redefinition of the QM and MM regions during the simulation and reducing QM-MM interface errors by discarding forces near the boundary according to the buffered force-mixing approach. New adaptive thermostats, needed by force-mixing methods, are also implemented. Different variants of the method are benchmarked by simulating the structure of bulk water, water autoprotolysis in the presence of zinc and dimethyl-phosphate hydrolysis using various semiempirical Hamiltonians and density functional theory as the QM model. It is shown that with suitable parameters, based on force convergence tests, the AdBF QM/MM scheme can provide an accurate approximation of the structure in the dynamical QM region matching the corresponding fully QM simulations, as well as reproducing the correct energetics in all cases. Adaptive unbuffered force-mixing and adaptive conventional QM/MM methods also provide reasonable results for some systems, but are more likely to suffer from instabilities and inaccuracies.N.B. acknowledges funding for this work by the Office of Naval Research through the Naval Research Laboratory's basic research program, and computer time at the AFRL DoD Supercomputing Resource Center through the DoD High Performance Computing Modernization Program (subproject NRLDC04253428). B.L. was supported by EPSRC (grant no. EP/G036136/1) and the Scottish Funding Council. G.C. and B.L. acknowledge support form EPSRC under grant no. EP/J01298X/1. R.C.W. and A.W.G. acknowledge financial support by the National Institutes of Health (R01 GM100934), A.W.G. acknowledges financial support by the Department of Energy (DE-AC36-99GO-10337). This work was partially supported by National Science Foundation (grant no. OCI-1148358) and used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant no. ACI-1053575. Computer time was provided by the San Diego Supercomputer Center through XSEDE award TG-CHE130010.This is the author accepted version of the article. The final published version is available from Wiley at http://onlinelibrary.wiley.com/doi/10.1002/jcc.23839/full

Chiral 1,5-disubstituted 1,2,3-triazoles-versatile tools for foldamers and peptidomimetic applications

1,4- A nd 1,5-Disubstituted triazole amino acid monomers have gained increasing interest among peptidic foldamers, as they are easily prepared via Cu- A nd Ru-catalyzed click reactions, with the potential for side chain variation. While the latter is key to their applicability, the synthesis and structural properties of the chiral mono-or disubstituted triazole amino acids have only been partially addressed. We here present the synthesis of all eight possible chiral derivatives of a triazole monomer prepared via a ruthenium-catalyzed azide alkyne cycloaddition (RuAAC). To evaluate the conformational properties of the individual building units, a systematic quantum chemical study was performed on all monomers, indicating their capacity to form several low energy conformers. This feature may be used to effect structural diversity when the monomers are inserted into various peptide sequences. We envisage that these results will facilitate new applications for these artificial oligomeric compounds in diverse areas, ranging from pharmaceutics to biotechnology

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Fitness benefits of prolonged post-reproductive lifespan in women

Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

Tuning of Human Modulation Filters Is Carrier-Frequency Dependent

Licensed under the Creative Commons Attribution License

High Level of Pyrethroid Resistance in an Anopheles funestus Population of the Chokwe District in Mozambique

Background Although Anopheles funestus is difficult to rear, it is crucial to analyse field populations of this malaria vector in order to successfully characterise mechanisms of insecticide resistance observed in this species in Africa. In this study we carried out a large-scale field collection and rearing of An. funestus from Mozambique in order to analyse its susceptibility status to insecticides and to broadly characterise the main resistance mechanisms involved in natural populations. Methodology/Principal Findings 3,000 F1 adults were obtained through larval rearing. WHO susceptibility assays indicated a very high resistance to pyrethroids with no mortality recorded after 1h30min exposure and less than 50% mortality at 3h30min. Resistance to the carbamate, bendiocarb was also noted, with 70% mortality after 1h exposure. In contrast, no DDT resistance was observed, indicating that no kdr-type resistance was involved. The sequencing of the acetylcholinesterase gene indicated the absence of the G119S and F455W mutations associated with carbamate and organophosphate resistance. This could explain the absence of malathion resistance in this population. Both biochemical assays and quantitative PCR implicated up-regulated P450 genes in pyrethroid resistance, with GSTs playing a secondary role. The carbamate resistance observed in this population is probably conferred by the observed altered AChE with esterases also involved. Conclusion/Significance The high level of pyrethroid resistance in this population despite the cessation of pyrethroid use for IRS in 1999 is a serious concern for resistance management strategies such as rotational use of insecticides. As DDT has now been re-introduced for IRS, susceptibility to DDT needs to be closely monitored to prevent the appearance and spread of resistance to this insecticide

Synergies for Improving Oil Palm Production and Forest Conservation in Floodplain Landscapes

Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates ($413/ha?yr–$637/ha?yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of $-299/ha?yr-$-65/ha?yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes

Symptomatic hemorrhage after alteplase therapy not due to silent ischemia

BACKGROUND: Stroke thrombolysis-related intracerebral hemorrhage may occur remotely from the anatomical site of ischemia. One postulated mechanism for this is simultaneous multiple embolization with hemorrhage into a "silent" area of ischemia. RESULTS: A patient suffered a disabling stroke affecting the right cerebral hemisphere. He was treated with intravenous alteplase and underwent extensive early imaging with multimodal MRI. Several hours after treatment he developed a brainstem hemorrhage despite having no evidence of ischemia on DWI MRI in the brainstem. CONCLUSION: Not all occurrences of remote ICH after stroke thrombolysis are secondary to multiple emboli with silent ischemia