Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.

Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.

Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).

Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.

Impact of average household income and damage exposure on post-earthquake distress and functioning: A community study following the February 2011 Christchurch earthquake.

Post-traumatic stress, depression and anxiety symptoms are common outcomes following earthquakes, and may persist for months and years. This study systematically examined the impact of neighbourhood damage exposure and average household income on psychological distress and functioning in 600 residents of Christchurch, New Zealand, 4–6 months after the fatal February, 2011 earthquake. Participants were from highly affected and relatively unaffected suburbs in low, medium and high average household income areas. The assessment battery included the Acute Stress Disorder Scale, the depression module of the Patient Health Questionnaire (PHQ-9), and the Generalized Anxiety Disorder Scale (GAD-7), along with single item measures of substance use, earthquake damage and impact, and disruptions in daily life and relationship functioning. Controlling for age, gender and social isolation, participants from low income areas were more likely to meet diagnostic cut-offs for depression and anxiety, and have more severe anxiety symptoms. Higher probabilities of acute stress, depression and anxiety diagnoses were evident in affected versus unaffected areas, and those in affected areas had more severe acute stress, depression and anxiety symptoms. An interaction between income and earthquake effect was found for depression, with those from the low and medium income affected suburbs more depressed. Those from low income areas were more likely, post-earthquake, to start psychiatric medication and increase smoking. There was a uniform increase in alcohol use across participants. Those from the low income affected suburb had greater general and relationship disruption post-quake. Average household income and damage exposure made unique contributions to earthquake-related distress and dysfunction.

Earthquake aftershock anxiety: An examination of psychosocial contributing factors and symptomatic outcomes.

This study examined the direct and indirect effects of cognitions and anxiety associated with aftershocks on psychological symptoms (anxiety, depression, acute stress) and daily functioning (general and relationship). Participants were 600 adults from Christchurch. Data collection was approximately four months after the fatal 2011 earthquake. Path analysis was used. Socioeconomic status was directly associated with appraisals of uncontrollability of response to aftershocks. These cognitions were directly related to aftershock anxiety, which heightened general anxiety, depression and acute stress symptoms. These symptoms were directly associated with relationship and general life dysfunction. Aftershock anxiety plays a significant role in ongoing psychological distress associated with earthquakes.

A simplified procedure for sizing solar thermal systems based on national assessment methods in the UK and Ireland.

Solar heating systems have the potential to be an efficient renewable energy technology, provided they are sized correctly. Sizing a solar thermal system for domestic applications does not warrant the cost of a simulation. As a result simplified sizing procedures are required. The size of a system depends on a number of variables including the efficiency of the collector itself, the hot water demand and the solar radiation at a given location. Domestic Hot Water (DHW) demand varies with time and is assessed using a multi-parameter detailed model. Secondly, the national energy evaluation methodologies are evaluated from the perspective of solar thermal system sizing. Based on the assessment of the standards, limitations in the evaluation method for solar thermal systems are outlined and an adapted method, specific to the sizing of solar thermal systems, is proposed. The methodology is presented for two common dwelling scenarios. Results from this showed that it is difficult to achieve a high solar fraction given practical sizes of system infrastructure (storage tanks) for standard domestic properties. However, solar thermal systems can significantly offset energy loads due associated DHW consumption, particularly when sized appropriately. The presented methodology is valuable for simple solar system design and also for the quick comparison of salient criteria.

Demand-side characterisation of the smart city for energy modelling.

This paper presents a new methodology for characterising the energy performance of buildings suitable for city-scale, top-down energy modelling. Building properties that have the greatest impact on simulated energy performance were identified via a review of sensitivity analysis studies. The methodology greatly simplifies the description of a building to decrease labour and simulation processing overheads. The methodology will be used in the EU FP7 INDICATE project which aims to create a master-planning tool that uses dynamic simulation to facilitate the design of sustainable, energy efficient smart cities.

TAP Reactor Development and Application in the Kinetic Characterization of Catalysts for Heterogeneously Catalyzed Gas Phase Reactions

This manuscript describes the application and further development of the TAP technique in kinetic characterization of heterogeneous catalysis. The major application of TAP systems is to study mechanisms, kinetics and transport phenomena in heterogeneous catalysis, all of which is made possible by the sub-millisecond time resolution. Furthermore, the kinetic information obtained can be used to gain an insight into the mechanism occurring over the catalyst system. This is advantageous as heterogeneous catalysts with an improved efficiency can be developed as a result. TAP kinetic studies are carried out at low pressure (~1x10-7 mbar) and TAP pulses are sufficiently small (1013-1015 molecules) so as to maintain this low pressure. The use of a small number of molecules in comparison to the total number of active sites means the state of the catalyst remains relatively unchanged. The use of the low intensity pulses also makes the pressure gradient negligible and so allows the TAP reactor system to operate in the Knudsen Diffusion regime, where gas-gas reactions are eliminated. Hence only gas-catalyst reactions are investigated and, by the use of moment analysis of observed exit flow, rate constants of elementary steps of the reaction can be obtained.

In this manuscript, two attempts to further the TAP technique are reported. Firstly, the work undertaken at QUB to attempt to control the number of molecules of condensable reagents that can be pulsed during a TAP pulse experiment is disclosed. Secondly, a collaborative project with SAI Ltd Manchester is discussed in a separate chapter, where technical details and validation of a customised time of flight mass spectrometer (ToF MS) for the QUB TAP-1 system are reported. A collaborative project with Cardiff Catalysis Institute focusing on the study of CO oxidation over hopcalite catalysts is also reported. The analysis of the experimental results has provided an insight into the possible mechanism of the oxidation of CO over these catalysts. A correction function has also been derived which accounts for the adsorption of reactant molecules over inert materials that are used for the reactor packing in TAP experiments. This function was then applied to the selective reduction of O2 in a H2 rich ethene feed, so that more accurate TAP moment based analysis could be conducted.

The influence of area level social deprivation on preoperative disease severity and postoperative outcomes following unicompartmental knee joint replacement

BACKGROUND: This study investigated the effect of socioeconomic deprivation on preoperative disease and outcome following unicompartmental knee replacement (UKR).

METHODS: 307 Oxford UKRs implanted between 2008 and 2013 under the care of one surgeon using the same surgical technique were analysed. Deprivation was quantified using the Northern Ireland Multiple Deprivation Measure. Preoperative disease severity and postoperative outcome were measured using the Oxford Knee Score (OKS).

RESULTS: There was no difference in preoperative OKS between deprivation groups. Preoperative knee range of motion (ROM) was significantly reduced in more deprived patients with 10° less ROM than least deprived patients. Postoperatively there was no difference in OKS improvement between deprivation groups (p=0.46), with improvements of 19.5 and 21.0 units in the most and least deprived groups respectively. There was no significant association between deprivation and OKS improvement on unadjusted or adjusted analysis. Preoperative OKS, Short Form 12 mental component score and length of stay were significant independent predictors of OKS improvement. A significantly lower proportion of the most deprived group (15%) reported being able to walk an unlimited distance compared to the least deprived group (41%) one year postoperatively.

CONCLUSION: More deprived patients can achieve similar improvements in OKS to less deprived patients following UKR.

LEVEL OF EVIDENCE: 2b - retrospective cohort study of prognosis.

Comparing Social Work Students' Perceptions of Risk Using Online Discussion Fora: Lessons Learned from a European Pilot Project

Comparisons of international child welfare systems have identified two basic orientations to practice; a ‘child protection’ orientation and a ‘child welfare’ orientation, which are founded upon fundamentally different values and assumptions regarding the family, the origins of child care problems, and the proper role of the state in relation to the family. This paper describes a project which sought to compare how undergraduate social work students from three European Universities perceive risk in referrals about the welfare of children and to explore the impact of different cultural, ideological and educational contexts on the way in which risk is constructed by students. Students from Northern Ireland, Germany and Poland examined three vignettes via ten online discussion fora each of which provided a narrative summary of their discussion. The paper presents some findings from the analysis of the qualitative data emerging from the student discussions and draws out the lessons learned in terms of how the project was designed and implemented using online discussion fora.

Parker Morris and the Fordist House

6.00 pm. If people like watching T.V. while they are eating their evening meal, space for a low table is needed (Ministry of Housing and Local Government, Space in the Home, 1963, p. 4).

This paper re-examines the 1961 Parker Morris report on housing standards in Britain. It explores the origins, scope, text and iconography of the report and suggests that these not only express a particularly modernist conception of space but one which presupposed very specific economic conditions and geographies.

Also known as Homes for Today and Tomorrow Parker Morris attempted, through the application of scientific principles, to define the minimum living space standards needed to accommodate household activities. But while early modernist research into notions of existenzminimum were the work of avant-garde architects and thinkers, Homes for Today and Tomorrow and its sister design manual Space in the Home were commissioned by the British State. This normalization of scientific enquiry into space can be considered not only as a response to new conditions in the mass production of housing – economies of scale, prefabrication, system-building and modular coordination – but also to the post-war boom in consumer goods. In this, it is suggested that the domestic interior was assigned a key role as a privileged site of mass consumption as the production and micro-management of space in Britain became integral to the development of a planned national economy underpinned by Fordist principles. Parker Morris, therefore, sought to accommodate activities which were pre-determined not so much by traditional social or familial ties but rather by recently introduced commodities such as the television set, white goods, table tennis tables and train sets. This relationship between the domestic interior and the national economy are emblematized by the series of placeless and scale-less diagrams executed by Gordon Cullen in Space in the Home. Here, walls dissolve as space flows from inside to outside in a homogenized and ephemeral landscape whose limits are perhaps only the boundaries of the nation state and the circuits of capital.

In Britain, Parker Morris was the last explicit State-sponsored attempt to prescribe a normative spatial programme for national living. The calm neutral efficiency of family-life expressed in its diagrams was almost immediately problematised by the rise of 1960s counter-culture, the feminist movement and the oil crisis of 1972 which altered perhaps forever the spatial, temporal and economic conditions it had taken for granted. The debate on space-standards, however, continues.