Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD. METHODS: In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness. RESULTS: A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E. CONCLUSIONS: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

Modelling of aircraft manufacturing cost at the concept stage

The work presented is concerned with the estimation of manufacturing cost at the concept design stage, when little technical information is readily available. The work focuses on the nose cowl sections of a wide range of engine nacelles built at Bombardier Aerospace Shorts of Belfast. A core methodology is presented that: defines manufacturing cost elements that are prominent; utilises technical parameters that are highly influential in generating those costs; establishes the linkage between these two; and builds the associated cost estimating relations into models. The methodology is readily adapted to deal with both the early and more mature conceptual design phases, which thereby highlights the generic, flexible and fundamental nature of the method. The early concept cost model simplifies cost as a cumulative element that can be estimated using higher level complexity ratings, while the mature concept cost model breaks manufacturing cost down into a number of constituents that are each driven by their own specific drivers. Both methodologies have an average error of less that ten percent when correlated with actual findings, thus achieving an acceptable level of accuracy. By way of validity and application, the research is firmly based on industrial case studies and practice and addresses the integration of design and manufacture through cost. The main contribution of the paper is the cost modelling methodology. The elemental modelling of the cost breakdown structure through materials, part fabrication, assembly and their associated drivers is relevant to the analytical design procedure, as it utilises design definition and complexity that is understood by engineers.

The WASP project in the era of robotic telescope networks

We present the current status of the WASP project, a pair of wide angle photometric telescopes, individually called SuperWASP. SuperWASP-I is located in La Palma, and SuperWASP-II at Sutherland in South Africa. SW-I began operations in April 2004. SW-II is expected to be operational in early 2006. Each SuperWASP instrument consists of up to 8 individual cameras using ultra-wide field lenses backed by high-quality passively cooled CCDs. Each camera covers 7.8 x 7.8 sq degrees of sky, for nearly 500 sq degrees of total sky coverage. One of the current aims of the WASP project is the search for extra-solar planet transits with a focus on brighter stars in the magnitude range similar to 8 to 13. Additionally, WASP will search for, optical transients, track Near-Earth Objects, and study many types of variable stars and extragalactic objects. The collaboration has developed a custom-built reduction pipeline that achieves better than I percent photometric precision. We discuss future goals, which include: nightly on-mountain reductions that could be used to automatically drive alerts via a small robotic telescope network, and possible roles of the WASP telescopes as providers in such a network. Additional technical details of the telescopes, data reduction, and consortium members and institutions can be found on the web site at: http://www.superwasp.org/. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recognizing and reporting child physical abuse: a cross sectional survey of primary health care professionals

Objectives: To assess primary health care professionalsâ?? ability to recognise child physical abuse within their everyday practice. Design: Cross-sectional survey Participants: A stratified random sample of 979 nurses, doctors, and dentists working in primary care in NI. Results: Four hundred and thirty one primary health care professionals responded [44% response rate]. Thirty two per cent were doctors, 35% were dentists and 33% were nurse professionals. The mean age was 41.63 years. Fifty-nine percent (251) stated that they had seen a suspicious case of child physical abuse and 47% (201) said they had reported it. Seventy-two per cent (310) of participants were aware of the mechanisms for reporting child physical abuse. Ability and willingness to recognise and report abuse discriminated the three professions. Conclusions: The findings suggest a professional reluctance to engage in recognising and reporting abuse. Barriers could be reduced by providing training and professional support for the primary care professionals.

Hydrocarbon Anions in Interstellar Clouds and Circumstellar Envelopes

The recent detection of the hydrocarbon anion C$_6$H$^-$ in the interstellar medium has led us to investigate the synthesis of hydrocarbon anions in a variety of interstellar and circumstellar environments. We find that the anion/neutral abundance ratio can be quite large, on the order of at least a few percent, once the neutral has more than five carbon atoms. Detailed modeling shows that the column densities of C$_6$H$^-$ observed in IRC+10216 and TMC-1 can be reproduced. Our calculations also predict that other hydrocarbon anions, such as C$_{4}$H$^{-}$ and C$_8$H$^-$, are viable candidates for detection in IRC+10216, TMC-1 and photon-dominated regions such as the Horsehead Nebula.

Extension of the Ye and Shreeve group contribution method for density estimation of ionic liquids in a wide range of temperatures and pressures

An extension of the Ye and Shreeve group contribution method [C. Ye, J.M. Shreeve, J. Phys. Chem. A 111 (2007) 1456–1461] for the estimation of densities of ionic liquids (ILs) is here proposed. The new version here presented allows the estimation of densities of ionic liquids in wide ranges of temperature and pressure using the previously proposed parameter table. Coefficients of new density correlation proposed were estimated using experimental densities of nine imidazolium-based ionic liquids. The new density correlation was tested against experimental densities available in literature for ionic liquids based on imidazolium, pyridinium, pyrrolidinium and phosphonium cations. Predicted densities are in good agreement with experimental literature data in a wide range of temperatures (273.15–393.15 K) and pressures (0.10–100 MPa). For imidazolium-based ILs, the mean percent deviation (MPD) is 0.45% and 1.49% for phosphonium-based ILs. A low MPD ranging from 0.41% to 1.57% was also observed for pyridinium and pyrrolidinium-based ILs.

Applying a QSPR correlation to the prediction of surface tensions of ionic liquids

Ionic liquids (ILs) have attracted large amount of interest due to their unique properties. Although large effort has been focused on the investigation of their potential application, characterization of ILs properties and structure–property relationships of ILs are poorly understood. Computer aided molecular design (CAMD) of ionic liquids (ILs) can only be carried if predictive computational methods for the ILs properties are available. The limited availability of experimental data and their quality have been preventing the development of such tools. Based on experimental surface tension data collected from the literature and measured at our laboratory, it is here shown how a quantitative structure–property relationship (QSPR) correlation for parachors can be used along with an estimation method for the densities to predict the surface tensions of ILs. It is shown that a good agreement with literature data is obtained. For circa 40 ionic liquids studied a mean percent deviation (MPD) of 5.75% with a maximum deviation inferior to 16% was observed. A correlation of the surface tensions with the molecular volumes of the ILs was developed for estimation of the surface tensions at room temperature. It is shown that it can describe the experimental data available within a 4.5% deviation. The correlations here developed can thus be used to evaluate the surface tension of ILs for use in process design or in the CAMD of new ionic liquids.

A group contribution method for viscosity estimation of ionic liquids

Based on experimental viscosity data collected from the literature and using density data obtained from a predictive method previously proposed by the authors, a group contribution method is proposed to estimate viscosity of imidazolium-, pyridinium-, and pyrrolidinium-based ILs containing hexafluorophosphate (PF6), tetrafluoroborate (BF4), bis(trifluoromethanesulfonyl) amide (Tf2N), chloride (Cl), acetate (CH3COO), methyl sulfate (MeSO4), ethyl sulfate (EtSO4), and trifluoromethanesulfonate (CF3SO3) anions, covering wide ranges of temperature, 293–393 K and viscosity, 4–21,000 cP. It is shown that a good agreement with literature data is obtained. For circa 500 data points of 29 ILs studied, a mean percent deviation (MPD) of 7.7% with a maximum deviation smaller than 28% was observed. 71.1% of the estimated viscosities present deviations smaller than 10% of the experimental values while only 6.4% have deviations larger than 20%. The group contribution method here developed can thus be used to evaluate the viscosity of new ionic liquids in wide ranges of temperatures at atmospheric pressure and, as data for new groups of cations and anions became available, can be extended to a larger range of ionic liquids.

Estimation of speed of sound of ionic liquids using surface tensions and densities: A volume based approach

The limited availability of experimental data and their quality have been preventing the development of predictive methods and Computer Aided Molecular Design (CAMD) of ionic liquids (ILs). Based on experimental speed of sound data collected from the literature, the inter-relationship of surface tension (s), density (?), and speed of sound (u) has been examined for imidazolium based ILs containing hexafluorophosphate (PF6), tetrafluoroborate (BF4), bis(trifluoromethanesulphonyl) amide (NTf2), methyl sulphate (MeSO4), ethyl sulphate (EtSO4), and trifluoromethanesulphonate (CF3SO3) anions, covering wide ranges of temperature, 278.15–343.15 K and speed of sound, 1129.0–1851.0 m s-1. The speed of sound was correlated with a modified Auerbach's relation, by using surface tension and density data obtained from volume based predictive methods previously proposed by the authors. It is shown that a good agreement with literature data is obtained. For 133 data points of 14 ILs studied a mean percent deviation (MPD) of 1.96% with a maximum deviation inferior to 5% was observed. The correlations developed here can thus be used to evaluate the speeds of sound of new ionic liquids.

Oesophageal cancer: caregiver mental health and strain

Objective: To investigate strain and mental health among family caregivers of oesophageal cancer patients and possible factors associated with caregiver mental health and strain.

Methods: Patients with oesophageal adenocarcinoma in Ireland were recruited into the FINBAR study (the main aim of which was to investigate factors influencing the Barrett's adenocarcinoma relationship). Carers completed the 13-item Caregiver Strain Index and the General Health Questionnaire-30 (GHQ) in the context of a brief interview with trained research staff that was undertaken separately from the interview with each cancer patient.

Results: Two hundred and twenty-seven patients participated in the FINBAR study. A total of 39 patients did not have a family carer or the carer could not be identified. Fifty percent (94/188) of carers completed the questionnaires. Mean (SD) scores for strain (6.65, SD=3.63) and mental health status (10.21, SD=7.30) were high and 71% of carers scored >5 on the GHQ indicating psychological distress. There was a statistically significant positive relationship between level of strain experienced by caregivers and the severity of their mental health status and whether or not carers scored >5 on the GHQ. Relatives were 1.70 (95% CI 1.34-2.15) times more likely to be defined as high scorers with each unit increase in the CSI score.

Conclusions: A significant proportion of caregivers experienced high levels of strain and psychological distress. There is a need to provide appropriate support and services targeted specifically at reducing the considerable strain of caring for patients with oesophageal cancer, particularly for carers of patients from lower socioeconomic groups.

The prevalence of nonadherence in difficult asthma

Rationale: With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported.

Objectives: To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome.

Methods: General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting ß-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence.

Measurements and Main Results: A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent.

Conclusions: A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies.

Recognising the co-occurance of domestic and child abuse: a comparison of community and hospital-based midwives

This study aimed to compare and contrast how midwives working in either hospital or community settings are currently responding to the cooccurrence of domestic and child abuse (CA), their perceived role and willingness to identify abuse, record keeping, reporting of suspected or definite cases of CA and training received. A survey questionnaire was sent to 861 hospital and community midwives throughout Northern Ireland which resulted in 488 midwives completing the questionnaire, leading to a 57% response rate. Comparisons were made using descriptive statistics and cross-tabulation, and the questionnaire was validated using exploratory factor analysis. Community midwives reported receiving more training on domestic and CA. Although a high percent of both hospital and community midwives acknowledged a link between domestic violence (DV) and CA, it was the community midwives who encountered more suspected and definite (P <0.001) cases of CA. More community midwives reported to be aware of the mechanisms for reporting CA. However, an important finding is that although 12% of community midwives encountered a definite case of CA, only 2% reported the abuse, leaving a 10% gap between reporting and identifying definite cases of CA. Findings suggest that lack of education and training was a problem as only a quarter of hospital-based midwives reported to have received training on DV and 40% on CA. This was significantly less than that received by community midwives, as 57% received training on DV, and 62% on CA. The study suggests that midwives need training on how to interact with abused mothers using non-coercive, supportive and empowering mechanisms. Many women may not spontaneously disclose the issues of child or domestic abuse in their lives, but often respond honestly to a sensitively asked question. This issue is important as only 13% of the sample actually asked a woman a direct question about DV.

A national survey of the mangement of delirium in UK intensive care units

Background: Delirium is an acute organ dysfunction common amongst patients treated in intensive care units. The associated morbidity and mortality are known to be substantial. Previous surveys have described which screening tools are used to diagnose delirium and which medications are used to treat delirium, but these data are not available for the United Kingdom. Aim: This survey aimed to describe the UK management of delirium by consultant intensivists. Additionally, knowledge and attitudes towards management of delirium were sought. The results will inform future research in this area. Methods: A national postal survey of members of the UK Intensive Care Society was performed. A concise two page questionnaire survey was sent, with a second round of surveys sent to non-respondents after 6 weeks. The questionnaire was in tick-box format. Results: Six hundred and eighty-one replies were received from 1308 questionnaires sent, giving a response rate of 52%. Twenty-five percent of respondents routinely screen for delirium, but of these only 55% use a screening tool validated for use in intensive care. The majority (80%) of those using a validated instrument used the Confusion Assessment Method for the Intensive Care Unit. Hyperactive delirium is treated pharmacologically by 95%; hypoactive delirium is treated pharmacologically by 25%, with haloperidol the most common agent used in both. Over 80% of respondents agreed that delirium prolongs mechanical ventilation and hospital stay and requires active treatment. Conclusions: This UK survey demonstrates screening for delirium is sporadic. Pharmacological treatment is usually with haloperidol in spite of the limited evidence to support this practice. Hypoactive delirium is infrequently treated pharmacologically.

The cost-effectiveness of the SPHERE intervention for the secondary prevention of coronary heart disease

Objectives: The Secondary Prevention of Heart disEase in geneRal practicE (SPHERE) trial has recently reported. This study examines the cost-effectiveness of the SPHERE intervention in both healthcare systems on the island of Ireland. Methods: Incremental cost-effectiveness analysis. A probabilistic model was developed to combine within-trial and beyond-trial impacts of treatment to estimate the lifetime costs and benefits of two secondary prevention strategies: Intervention - tailored practice and patient care plans; and Control - standardized usual care. Results: The intervention strategy resulted in mean cost savings per patient of 512.77 (95 percent confidence interval [CI], 1086.46-91.98) and an increase in mean quality-adjusted life-years (QALYs) per patient of 0.0051 (95 percent CI, 0.0101-0.0200), when compared with the control strategy. The probability of the intervention being cost-effective was 94 percent if decision makers are willing to pay €45,000 per additional QALY. Conclusions: Decision makers in both settings must determine whether the level of evidence presented is sufficient to justify the adoption of the SPHERE intervention in clinical practice. Copyright © Cambridge University Press 2010.

European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

PURPOSE:
Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients.
PATIENTS AND METHODS:
Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy.
RESULTS:
A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival.
CONCLUSION:
Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.