ESTIMATING THE SUBJECT BY TREATMENT INTERACTION IN NON-REPLICATED CROSSOVER DIET STUDIES

Researchers in human nutrition commonly refer to the ‘consistent’ diet effect (i.e. the main effect of diet) and an ‘inconsistent’ diet effect (i.e. a subject by diet interaction). However, due to the non-replicated designs of most studies, one can only estimate the first part using ANOVA; the latter (interaction) is confounded with the residual noise. In many diet studies, it appears that subjects do respond differently to the same diet, so the subject by diet interaction may be large. In a search of over 40,000 published human nutrition studies, most using a crossover design, we found that in none was a subject by diet interaction effect estimated. For this paper, we examined LDL-cholesterol data from a non-replicated crossover study with four diets, the typical American diet, with and without added plant sterols, and a cholesterol-lowering Step-1 diet, with and without sterols. We also examined LDL-cholesterol data from a second crossover study with some replications with three diets, representing the daily supplement of 0, 1 or 2 servings of pistachio nuts. These two data sets were chosen because experience suggested that LDLcholesterol responses to diet tend to be subject-specific. The second data set, with some replication, allowed us to estimate the subject by diet interaction term in a traditional ANOVA framework. One approach to estimating an interaction effect in non-replicated studies is through the use of a multiplicative decomposition of the interaction (sometimes called AMMI―additive main effects, multiplicative interaction). In this type of analysis, residuals, formed after estimated main effects are subtracted from the data, are arrayed in a matrix with diets as columns and subjects as rows. A singular value decomposition of the matrix is performed and the first, or first and second, principal component(s) are used as estimates of the interaction, and can be tested for significance using approximate F-tests. Using the R gnm package, we found large and significant subject by diet interaction effects in both data sets; estimates of the interaction in the second data set were similar to interaction estimates from traditional ANOVA. Of an additional 26 dependent variables from the first and a third data set (the latter investigating the effect of mild alcohol consumption on blood variables), 19 had significant subject by diet interactions, based on the AMMI methodology. These results suggest that the subject by diet interaction is often important and should not be ignored when analyzing data obtained from non-replicated crossover designs―the AMMI methodology works well and is readily available in statistical software packages

Perinatal Hypoxic-Ischemic Brain Injury Enhances Quisqualic Acid-Stimulated Phosphoinositide Turnover

In an experimental model of perinatal hypoxic-ischemic brain injury, we examined quisqualic acid (Quis)-stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7-day-old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis-stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic-ischemic injury. The glutamate agonist Quis (10 -4 M ) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 ± 237% of basal, mean ± SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 ± 134%) and by about sixfold in controls (631 ± 177%, p < 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 ± 157%, 474 ± 89%, and 506 ± 115% (p < 0.05). In contrast, stimulation of PPI turnover elicited by the cho-linergic agonist carbamoylcholine, (10 -4 or 10 -2 M ) was unaffected by hypoxia-ischemia. The results suggest that prior exposure to hypoxia-ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66017/1/j.1471-4159.1988.tb01046.x.pd

Magnetopause Reconnection as Influenced by the Dipole Tilt Under Southward IMF Conditions: Hybrid Simulation and MMS Observation

Using a three‐dimensional (3‐D) global‐scale hybrid code, the Magnetospheric Multiscale (MMS) reconnection event around 02:13 UT on 18 November 2015, highlighted in the Geospace Environment Modeling (GEM) Dayside Kinetic Challenge, is simulated, in which the interplanetary magnetic field (IMF) points southward and the geomagnetic field has a −27° dipole tilt angle. Strong southward plasma jets are found near the magnetopause as a result of the dayside reconnection. Our results indicate that the subsolar magnetopause reconnection X line shifts from the subsolar point toward the Northern Hemisphere due to the effect of the tilted geomagnetic dipole angle, consistent with the MMS observation. Subsequently, the reconnection X lines or sites and reconnection flux ropes above the equator propagate northward along the magnetopause. The formation and global distribution of the X lines and the structure of the magnetopause reconnection are investigated in detail with the simulation. Mirror mode waves are also found in the middle of the magnetosheath downstream of the quasi‐perpendicular shock where the plasma properties are consistent with the mirror instability condition. As a special outcome of the GEM challenge event, the spatial and temporal variations in reconnection, the electromagnetic power spectra, and the associated D‐shaped ion velocity distributions in the simulated reconnection event are compared with the MMS observation.Key PointsSubsolar magnetopause X lines shift toward the Northern Hemisphere due to the effect of the negative tilted geomagnetic dipole angleThe hybrid simulation magnetic fields and plasma date match MMS3 observations well during the magnetopause crossingMirror mode waves appear in the middle of the magnetosheath downstream of the quasi‐perpendicular shockPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162687/2/jgra55909_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162687/1/jgra55909.pd

Using a Conceptual Site Model for Assessing the Sustainability of Brownfield Regeneration for a Soft Reuse:A Case Study of Port Sunlight River Park (U.K.)

Brownfield regeneration to soft reuse such as recreation and amenity has become increasingly common due to the demand for the potential environmental, social and economic benefits that it can deliver. This has led in turn to an increased demand for improved tools to support decision-making for this style of regeneration: tools which are simple to use, based on robust scientific principles and preferably which can ultimately link to quantitative or semi-quantitative cost-benefit analyses. This work presents an approach to assessing and comparing different scenarios for brownfield regeneration to soft reuse and other end-points. A “sustainability linkages” approach, based on sustainability assessment criteria produced by the UK Sustainable Remediation Forum (SuRF-UK), is developed and used in a refined qualitative sustainability assessment, and applied to develop a conceptual site model of sustainability, for a specific case study site (Port Sunlight River Park, U.K., a public leisure park established and maintained on a capped and managed former landfill site). Ranking, on an ex post basis, highlighted the clear sustainability advantages that the establishment of the Port Sunlight River Park has compared with a hypothetical non-development scenario. The conceptual site model provides a clearer basis for understanding cause and effect for benefits and disbenefits and a rationale for grouping individual effects based on their ease of valuation, providing a road map for cost-benefit assessments by (1) being able to match specific linkages to the most appropriate means of valuation, and (2) transparently connecting the sustainability assessment and cost benefit assessment processes.</p

Water sector service innovation: what, where and who?

Changes in water law and policy, in the UK and further afield, are promoting social and service innovation, as well as technical innovation in the water sector. In particular, the separation of wholesale and retail water and sewerage services for English and Welsh commercial water systems customers is leading to a focus on service innovation. But what do we mean by 'service innovation'? To whom does it apply and how do these parties interpret it? To answer these questions, this paper presents the findings of recent interviews undertaken by and case studies presented to the Water Efficiency (WATEF) Network Service Innovation Technical Committee

East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series

Academic geriatric medicine in Leicester . There has never been a better time to consider joining us. We have recently appointed a Professor in Geriatric Medicine, alongside Tom Robinson in stroke and Victoria Haunton, who has just joined as a Senior Lecturer in Geriatric Medicine. We have fantastic opportunities to support students in their academic pursuits through a well-established intercalated BSc programme, and routes on through such as ACF posts, and a successful track-record in delivering higher degrees leading to ACL post. We collaborate strongly with Health Sciences, including academic primary care. See below for more detail on our existing academic set-up. Leicester Academy for the Study of Ageing We are also collaborating on a grander scale, through a joint academic venture focusing on ageing, the ‘Leicester Academy for the Study of Ageing’ (LASA), which involves the local health service providers (acute and community), De Montfort University; University of Leicester; Leicester City Council; Leicestershire County Council and Leicester Age UK. Professors Jayne Brown and Simon Conroy jointly Chair LASA and have recently been joined by two further Chairs, Professors Kay de Vries and Bertha Ochieng. Karen Harrison Dening has also recently been appointed an Honorary Chair. LASA aims to improve outcomes for older people and those that care for them that takes a person-centred, whole system perspective. Our research will take a global perspective, but will seek to maximise benefits for the people of Leicester, Leicestershire and Rutland, including building capacity. We are undertaking applied, translational, interdisciplinary research, focused on older people, which will deliver research outcomes that address domains from: physical/medical; functional ability, cognitive/psychological; social or environmental factors. LASA also seeks to support commissioners and providers alike for advice on how to improve care for older people, whether by research, education or service delivery. Examples of recent research projects include: ‘Local History Café’ project specifically undertaking an evaluation on loneliness and social isolation; ‘Better Visits’ project focused on improving visiting for family members of people with dementia resident in care homes; and a study on health issues for older LGBT people in Leicester. Clinical Geriatric Medicine in Leicester We have developed a service which recognises the complexity of managing frail older people at the interface (acute care, emergency care and links with community services). There are presently 17 consultant geriatricians supported by existing multidisciplinary teams, including the largest complement of Advance Nurse Practitioners in the country. Together we deliver Comprehensive Geriatric Assessment to frail older people with urgent care needs in acute and community settings. The acute and emergency frailty units – Leicester Royal Infirmary This development aims at delivering Comprehensive Geriatric Assessment to frail older people in the acute setting. Patients are screened for frailty in the Emergency Department and then undergo a multidisciplinary assessment including a consultant geriatrician, before being triaged to the most appropriate setting. This might include admission to in-patient care in the acute or community setting, intermediate care (residential or home based), or occasionally other specialist care (e.g. cardiorespiratory). Our new emergency department is the county’s first frail friendly build and includes fantastic facilities aimed at promoting early recovering and reducing the risk of hospital associated harms. There is also a daily liaison service jointly run with the psychogeriatricians (FOPAL); we have been examining geriatric outreach to oncology and surgery as part of an NIHR funded study. We are home to the Acute Frailty Network, and those interested in service developments at the national scale would be welcome to get involved. Orthogeriatrics There are now dedicated hip fracture wards and joint care with anaesthetists, orthopaedic surgeons and geriatricians. There are also consultants in metabolic bone disease that run clinics. Community work Community work will consist of reviewing patients in clinic who have been triaged to return to the community setting following an acute assessment described above. Additionally, primary care colleagues refer to outpatients for sub-acute reviews. You will work closely with local GPs with support from consultants to deliver post-acute, subacute, intermediate and rehabilitation care services. Stroke Medicine 24/7 thrombolysis and TIA services. The latter is considered one of the best in the UK and along with the high standard of vascular surgery locally means one of the best performances regarding carotid intervention

The Joinpoint-Jump and Joinpoint-Comparability Ratio Model for Trend Analysis with Applications to Coding Changes in Health Statistics

Analysis of trends in health data collected over time can be affected by instantaneous changes in coding that cause sudden increases/decreases, or “jumps,” in data. Despite these sudden changes, the underlying continuous trends can present valuable information related to the changing risk profile of the population, the introduction of screening, new diagnostic technologies, or other causes. The joinpoint model is a well-established methodology for modeling trends over time using connected linear segments, usually on a logarithmic scale. Joinpoint models that ignore data jumps due to coding changes may produce biased estimates of trends. In this article, we introduce methods to incorporate a sudden discontinuous jump in an otherwise continuous joinpoint model. The size of the jump is either estimated directly (the Joinpoint-Jump model) or estimated using supplementary data (the Joinpoint-Comparability Ratio model). Examples using ICD-9/ICD-10 cause of death coding changes, and coding changes in the staging of cancer illustrate the use of these models

The Joinpoint-Jump and Joinpoint-Comparability Ratio Model for Trend Analysis with Applications to Coding Changes in Health Statistics

Analysis of trends in health data collected over time can be affected by instantaneous changes in coding that cause sudden increases/decreases, or “jumps,” in data. Despite these sudden changes, the underlying continuous trends can present valuable information related to the changing risk profile of the population, the introduction of screening, new diagnostic technologies, or other causes. The joinpoint model is a well-established methodology for modeling trends over time using connected linear segments, usually on a logarithmic scale. Joinpoint models that ignore data jumps due to coding changes may produce biased estimates of trends. In this article, we introduce methods to incorporate a sudden discontinuous jump in an otherwise continuous joinpoint model. The size of the jump is either estimated directly (the Joinpoint-Jump model) or estimated using supplementary data (the Joinpoint-Comparability Ratio model). Examples using ICD-9/ICD-10 cause of death coding changes, and coding changes in the staging of cancer illustrate the use of these models