The Detection of Change in Spatial Processes With Environmental Applications

Ever since Halley (1686) superimposed onto a map of land forms, the direction of trade winds and monsoons between and near the tropics and attempted to assign them a physical cause, homo-sapiens has attempted to develop procedures which quantify the level of change in a spatial process, or assess the relationship between associated spatially measured variables. Most spatial data, whether it be originally point, linear or areal in nature, can be converted by a suitable procedure into a continuous form and plotted as an isarithmic map i.e. points of equal height are joined. Once in that form it may be regarded as a statistical surface in which height varies over area in much the same way as the terrain varies on topographic maps. Particularly in environmental statistics, the underlying shape of the surface is unknown, and hence the use of non-parametric techniques is wholly appropriate. For most applications, the location of data points is beyond the control of the map-maker hence the analyst must cope with irregularly spaced data points. A variety of possible techniques for describing a surface are given in chapter two, with attention focusing on the methodology surrounding kernel density estimation. Once a surface has been produced to describe a set of data, a decision concerning the number of contours and how they should be selected has to be taken. When comparing two sets of data, it is imperative that the contours selected are chosen using the same criteria. A data based procedure is developed in chapter three which ensures comparability of the surfaces and hence spurious conclusions are not reached as a result of inconsistencies between surfaces. Contained within this chapter is a discussion of issues which relate to other aspects of how a contour should be drawn to minimise the potential for inaccuracies in the surface fitting methodology. Chapter four focuses on a whole wealth of techniques which are currently available for comparing surfaces. These range from the simplest method of overlaying two maps and visually comparing them to more involved techniques which require intensive numerical computation. It is the formalisation of the former of these techniques which forms the basis of the methodology developed in the following two chapters to discern whether change/association has materialised between variables. One means of quantifying change between two surfaces, represented as a contoured surface, is in terms of the transformation which would be required for the two surfaces to be matched. Mathematically, transformations are described in terms of rotation, translation and scalar change. Chapter five provides a geometrical interpretation of the three transformations in terms of area, perimeter, orientation and the centre of gravity of the contour of interest and their associated properties. Although grid resolution is fundamentally a secondary level of smoothing, this aspect of surface fitting has generally been ignored. However to ensure consistency across surfaces, it is necessary to decide firstly, whether data sets of different sizes should be depicted using different mesh resolutions and secondly, how fine a resolution provides optimal results, both in terms of execution time and inherent surface variability. This aspect is examined with particular reference to the geometric descriptors used to quantify change. The question of random noise contained within a measurement process has been ignored in the analysis to this point. However in practice, some form of noise will always be contained within a process. Quantifying the level of noise attributable to a process can prove difficult since the scientist may be over optimistic in his evaluation of the noise level. In developing a suitable set of test statistics, four situations were examined, firstly when no noise was present and then for three levels of noise, the upper bounds of which were 5,15 and 25%. Based on these statistics, a series of hypothesis tests were developed to look at the question of change for individual contour levels i.e. local analysis, or alternatively for a whole surface by combining the statistics and effectively performing a multivariate test

Optimisation of Cleaning Detergent use in Brewery Fermenter Cleaning

This paper investigates improvement possibilities in the cleaning operations undertaken at an industrial brewery. Experiments were performed on a bench scale cleaning rig which was designed to simulate ‘real life’ cleaning conditions of a clean-in-place (CIP) set in the brewery. The rig was used to clean consistently fouled coupons using difficult soils from the brewery. The objective of the experiments was to determine the reduction in effective cleaning performance with varied levels of Na2CO3 in the detergent from NaOH degradation and the maximum level that may be present before cleaning quality is impacted. The shear force of the cleaning fluid across the surface of the coupon was also varied to determine the impact on cleaning performance. Data collected from these offline measurements has been used to predict the end point of the detergent usage based on cost optimisation within the empirically determined limits. The results show that the NaOH detergent usage can be extended while achieving the same time to clean without impacting the cleaning quality and preventing premature disposal. This will provide an increased confidence level when cleaning fermenters with NaOH. It will also reduce cleaning costs and benefit the environment by reducing chemical effluent and minimising water consumption

Assessment of the Validity of Reported Antibiotic Allergic Reactions in Pediatric Patients

Study Objective. To determine whether a reported antibiotic allergy was likely to have been immunologically mediated. Design. Questionnaire-based study. Setting. Tertiary care, freestanding children\u27s hospital. Patients. One hundred patients aged 1 month-18 years for whom guardians reported an allergy to an antibiotic at the time of hospital admission between October 2009 and March 2010. Intervention. Guardians of the patients were interviewed by using a standardized allergy assessment questionnaire. Measurements and Main Results. Based on answers to the questionnaire, the reported allergic reactions were categorized to determine if they were true allergies or adverse reactions. Among the 100 patients, reported allergies were categorized as immunologically mediated reactions in 58%, non-immunologically mediated adverse drug reactions in 27%, no reaction in 3%, and unknown in 12%. Reactions to penicillins, cephalosporins, or sulfonamides were reported most frequently and were attributed to immunologically mediated reactions in 68% (26/38), 74% (17/23), and 67% (10/15) of instances, respectively. Conclusion. Use of the allergy assessment questionnaire determined that 58% of the 100 reported antibiotic allergies fulfilled criteria for an immunologically mediated reaction. These findings underscore the utility of an allergy assessment questionnaire, versus a simple drug history, in improving the accuracy of reported antibiotic reactions

Predicting asthma exacerbations employing remotely monitored adherence

This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant\u27s inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p \u3c 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events

A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma

ntroduction In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. Methods This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. Trial registration number NCT01529697; Pre-results

The effect of providing feedback on inhaler technique and adherence from an electronic audio recording device, INCA®, in a community pharmacy setting: study protocol for a randomised controlled trial.

BACKGROUND: Poor adherence to inhaled medication may lead to inadequate symptom control in patients with respiratory disease. In practice it can be difficult to identify poor adherence. We designed an acoustic recording device, the INCA® (INhaler Compliance Assessment) device, which, when attached to an inhaler, identifies and records the time and technique of inhaler use, thereby providing objective longitudinal data on an individual\u27s adherence to inhaled medication. This study will test the hypothesis that providing objective, personalised, visual feedback on adherence to patients in combination with a tailored educational intervention in a community pharmacy setting, improves adherence more effectively than education alone. METHODS/DESIGN: The study is a prospective, cluster randomised, parallel-group, multi-site study conducted over 6 months. The study is designed to compare current best practice in care (i.e. routine inhaler technique training) with the use of the INCA® device for respiratory patients in a community pharmacy setting. Pharmacies are the unit of randomisation and on enrolment to the study they will be allocated by the lead researcher to one of the three study groups (intervention, comparator or control groups) using a computer-generated list of random numbers. Given the nature of the intervention neither pharmacists nor participants can be blinded. The intervention group will receive feedback from the acoustic recording device on inhaler technique and adherence three times over a 6-month period along with inhaler technique training at each of these times. The comparator group will also receive training in inhaler use three times over the 6-month study period but no feedback on their habitual performance. The control group will receive usual care (i.e. the safe supply of medicines and advice on their use). The primary outcome is the rate of participant adherence to their inhaled medication, defined as the proportion of correctly taken doses of medication at the correct time relative to the prescribed interval. Secondary outcomes include exacerbation rates and quality of life measures. Differences in the timing and technique of inhaler use as altered by the interventions will also be assessed. Data will be analysed on an intention-to-treat and a per-protocol basis. Sample size has been calculated with reference to comparisons to be made between the intervention and comparator clusters and indicates 75 participants per cluster. With an estimated 10 % loss to follow-up we will be able to show a 20 % difference between the population means of the intervention and comparator groups with a power of 0.8. The Type I error probability associated with the test of the null hypothesis is 0.05. DISCUSSION: This clinical trial will establish whether providing personalised feedback to individuals on their inhaler use improves adherence. It may also be possible to enhance the role of pharmacists in clinical care by identifying patients in whom alteration of either therapy or inhaler device is appropriate. REGISTRATION: ClinicalTrials.gov NCT02203266

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patientsA2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels

Ozone exposure is associated with acute changes in inflammation, fibrinolysis, and endothelial cell function in coronary artery disease patients

Air pollution is a major risk factor for cardiovascular disease, of which ozone is a major contributor. Several studies have found associations between ozone and cardiovascular morbidity, but the results have been inconclusive. We investigated associations between ozone and changes across biological pathways associated with cardiovascular disease

Equality, Quasi-Implicit Products, and Large Eliminations

This paper presents a type theory with a form of equality reflection: provable equalities can be used to coerce the type of a term. Coercions and other annotations, including implicit arguments, are dropped during reduction of terms. We develop the metatheory for an undecidable version of the system with unannotated terms. We then devise a decidable system with annotated terms, justified in terms of the unannotated system. Finally, we show how the approach can be extended to account for large eliminations, using what we call quasi-implicit products.Comment: In Proceedings ITRS 2010, arXiv:1101.410