Commodification of retirement and the emergence of rural gated communities: The associated challenges for rural planning

Abstract:
This paper combines demographic ageing and retirement lifestyles with rural in-migration processes and suggests the emergence of a specific rural form of gated community; namely, park homes. All year round or permanent (as opposed to seasonal) residential mobile homes (resembling detached bungalows in design and appearance) are commonly referred to as 'park homes'. With a growing proportion of the UK population aged 65 and over, combined with increasing longevity, meeting the residential preferences and lifestyle aspirations of an ageing population is potentially 'big business' for the private sector. Park home living, with their resident age restrictions (normally 50 years and over), is increasingly marketed as a retirement option in rural and coastal locations of the UK. However, many areas are often remote with declining populations and limited community services. Operators have sought to tap into retiree aspirations for a 'place in the country' and 'sell' the concept of park home living as a specific form of housing, community and lifestyle. Park homes are frequently marketed as a means to release equity from the sale of a large family home to fund a retirement lifestyle and as friendly communities of like-minded people, always willing to lend support or provide assistance if required. The physical and social composition of such sites represent a form of rural gated community. This paper seeks to identify the rural planning issues which emerge from such developments and asks: who are moving to park home sites and why? do park homes provide those who otherwise could not afford a 'place in the country' the option of rural living? does park home living live-up to residents' expectations of the rural idyll or retirement lifestyle? do they give rise to issues of gentrification and geriatrification of the countryside? what are the prospects for residents to 'age in place'? might ageing residents become financially trapped in such developments giving rise to park ghettoization? what are the associated challenges for rural policy-makers and public service providers?

Enteric methane emissions and nitrogen utilisation efficiency for two genotype of hill hoggets offered fresh, ensiled and pelleted ryegrass

Thirty-six 12-month-old hill hoggets were used in a 2 genotype (18 Scottish Blackface vs. 18 Swaledale×Scottish Blackface)×3 diet (fresh vs. ensiled vs. pelleted ryegrass) factorial design experiment to evaluate the effects of hogget genotype and forage type on enteric methane (CH4) emissions and nitrogen (N) utilisation. The hoggets were offered 3 diets ad libitum with no concentrate supplementation in a single period study with 6 hoggets for each of the 6 genotype×diet combinations (n=6). Fresh ryegrass was harvested daily in the morning. Pelleted ryegrass was sourced from a commercial supplier (Aylescott Driers & Feeds, Burrington, UK) and the ryegrass silage was ensiled with Ecosyl (Lactobacillus plantarum, Volac International Limited, Hertfordshire, UK) as an additive. The hoggets were housed in individual pens for at least 14 d before being transferred to individual respiration chambers for a further 4 d with feed intake, faeces and urine outputs and CH4 emissions measured. There was no significant interaction between genotype and forage type on any parameter evaluated. Sheep offered pelleted grass had greater feed intake (e.g. DM, energy and N) but less energy and nutrient apparent digestibility (e.g. DM, N and neutral detergent fibre (NDF)) than those given fresh grass or grass silage (P<0.001). Feeding pelleted grass, rather than fresh grass or grass silage, reduced enteric CH4 emissions as a proportion of DM intake and gross energy (GE) intake (P<0.01). Sheep offered fresh grass had a significantly lower acid detergent fibre (ADF) apparent digestibility, and CH4 energy output (CH4-E) as a proportion of GE intake than those offered grass silage (P<0.001). There was no significant difference, in CH4 emission rate or N utilisation efficiency when compared between Scottish Blackface and Swaledale × Scottish Blackface. Linear and multiple regression techniques were used to develop relationships between CH4 emissions or N excretion and dietary and animal variables using data from sheep offered fresh ryegrass and grass silage. The equation relating CH4-E (MJ/d) to GE intake (GEI, MJ/d), energy apparent digestibility (DE/GE) and metabolisability (ME/GE) resulted in a high r2 (CH4-E=0.074 GEI+9.2 DE/GE−10.2 ME/GE−0.37, r2=0.93). N intake (NI) was the best predictor for manure N excretion (Manure N=0.66 NI+0.96, r2=0.85). The use of these relationships can potentially improve the precision and decrease the uncertainty in predicting CH4 emissions and N excretion for sheep production systems managed under the current feeding conditions.

Enhancing the Manufacturing Knowledge of Undergraduate Engineering Students: A Case Study of a Design-Build-Test Challenge Involving Folding Bicycles

Many engineers currently in professional practice will have gained a degree level qualification which involved studying a curriculum heavy with mathematics and engineering science. While this knowledge is vital to the engineering design process so also is manufacturing knowledge, if the resulting designs are to be both technically and commercially viable.
The methodology advanced by the CDIO Initiative aims to improve engineering education by teaching in the context of Conceiving, Designing, Implementing and Operating products, processes or systems. A key element of this approach is the use of Design-Built-Test (DBT) projects as the core of an integrated curriculum. This approach facilitates the development of professional skills as well as the application of technical knowledge and skills developed in other parts of the degree programme. This approach also changes the role of lecturer to that of facilitator / coach in an active learning environment in which students gain concrete experiences that support their development.
The case study herein describes Mechanical Engineering undergraduate student involvement in the manufacture and assembly of concept and functional prototypes of a folding bicycle.

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.

DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries.

SETTING: Eight European countries.

POPULATION: 14.8 million births 1990-2009; 2.89% multiple births.

METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.

MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.

STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time.

RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).

CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Behavior change theory, content and delivery of interventions to enhance adherence in chronic respiratory disease: A systematic review

Background: We sought to describe the theory used to design treatment adherence interventions, the content delivered, and the mode of delivery of these interventions in chronic respiratory disease. Methods: We included randomized controlled trials of adherence interventions (compared to another intervention or control) in adults with chronic respiratory disease (8 databases searched; inception until March 2015). Two reviewers screened and extracted data: post-intervention adherence (measured objectively); behavior change theory, content (grouped into psychological, education and self-management/supportive, telemonitoring, shared decision-making); and delivery. “Effective” studies were those with p < 0.05 for adherence rate between groups. We conducted a narrative synthesis and assessed risk of bias. Results: 12,488 articles screened; 46 included studies (n = 42,91% in OSA or asthma) testing 58 interventions (n = 27, 47% were effective). Nineteen (33%) interventions (15 studies) used 12 different behavior change theories. Use of theory (n = 11,41%) was more common amongst effective interventions. Interventions were mainly educational, self-management or supportive interventions (n = 27,47%). They were commonly delivered by a doctor (n = 20,23%), in face-to-face (n = 48,70%), one-to-one (n = 45,78%) outpatient settings (n = 46,79%) across 2–5 sessions (n = 26,45%) for 1–3 months (n = 26,45%). Doctors delivered a lower proportion (n = 7,18% vs n = 13,28%) and pharmacists (n = 6,15% vs n = 1,2%) a higher proportion of effective than ineffective interventions. Risk of bias was high in >1 domain (n = 43, 93%) in most studies. Conclusions: Behavior change theory was more commonly used to design effective interventions. Few adherence interventions have been developed using theory, representing a gap between intervention design recommendations and research practice.

Sharing the vision: representing the matters of concern for design-led fledgling companies in Scotland

Design is being performed on an ever-increasing spectrum of complex practices arising in response to emerging markets and technologies, co-design, digital interaction, service design and cultures of innovation. This emerging notion of design has led to an expansive array of collaborative and facilitation skills to demonstrate and share how such methods can shape innovation. The meaning of these design things in practice can't be taken for granted as matters of fact, which raises a key challenge for design to represent its role through the contradictory nature of matters of concern. This paper explores an innovative, object-oriented approach within the field of design research, visually combining an actor-network theory framework with situational analysis, to report on the role of design for fledgling companies in Scotland, established and funded through the knowledge exchange hub Design in Action (DiA). Key findings and visual maps are presented from reflective discussions with actors from a selection of the businesses within DiA's portfolio. The suggestion is that any notions of strategic value, of engendering meaningful change, of sharing the vision of design, through design things, should be grounded in the reflexive interpretations of matters of concern that emerge.

Determinants of self-medication with NSAIDs in a Portuguese community pharmacy

Background: Non-steroid anti-inflammatory drugs (NSAIDs) are a widely used therapeutic group in the world, and particularly in the Portuguese population. Objective: To compare NSAID’s use by prescription and self-medication acquisition and to determine the pattern of indication of NSAIDs, their usage profile and possible implications for patients’ safety. Methods: A cross-sectional design was used where individuals presenting at a community pharmacy requesting NSAIDs during the study period (one month) were invited to answer a face-to-face interview where socio-demographic characteristics, the indication pattern and previous experience of side effects were assessed. A follow-up interview was performed one week later to assess the incidence of adverse effects. The study was ethically approved. Results: A sample of 130 NSAIDs users was recruited, comprising mostly women (n=87; 66.9%), actively employed (n=77; 59.2%) and presenting a mean age of 49.5 years old (SD=20.49). An equal proportion of individuals acquired NSAIDs by self-medication and with medical prescription (n=65; 50%). Over 4/5 of patients (n=57; 87.7%) acquiring NSAIDs without a prescription were self-medicated by their own initiative, and only 10.8% (n=7) had been advised by the pharmacist. The most commonly acquired active substances were ibuprofen and diclofenac. Self-medicated users more frequently resorted to topical NSAIDs following short term treatments. The major underlying condition motivating NSAIDs sought were musculoskeletal disorders (45.0%), regardless of the regimen. An important proportion of prevalent users of NSAIDs reported previous experience of adverse effects (11.3%). One week after initiating NSAID therapy, a small proportion of patients reported incidence of adverse effects. Conclusion: Self-medication with NSAIDs is sought for numerous medical conditions. Reported adverse effects (prevalent and incident) confirm the need for a more rational use of NSAIDs and ongoing pharmacovigilance.

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the developing male Wistar(Han) rat I: no decrease in epididymal sperm count after a single acute dose

It has been reported that fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes defects in the male reproductive system of the rat. We set out to replicate and extend these effects using a robust experimental design. Groups of 75 (control vehicle) or 55 (50, 200 or 1000 ng of TCDD kg-1 bodyweight) female Wistar(Han) rats were exposed to TCDD on Gestational Day (GD) 15, then allowed to litter. The high dose group dams showed no sustained weight loss compared to control, but four animals had total litter loss. Pups in the high dose group showed reduced body weight up till day 21, and pups in the medium dose group showed reduced body weight in the first week post partum. Balano-preputial separation (BPS) was significantly delayed in the high dose group male offspring. There were no significant effects of treatment when the offspring were subjected to a functional observational battery, or mated with females to assess reproductive capability. 25 males per group were killed on post natal day (PND) 70, and ~60 animals per group (~30 for the high dose group) on PND120 to assess seminology and other endpoints. At PND120, the two highest dose groups showed a statistically significant elevation of sperm counts, compared to control; however, this effect was small (~30%), within the normal range of sperm counts for this strain of rat, was not reflected in testicular spermatid counts nor PND70 data, and is therefore postulated to have no biological significance. Although there was an increase in the proportion of abnormal sperm at PND70, seminology parameters were otherwise unremarkable. Testis weights in the high dose group were slightly decreased at PND 70 and 120, and at PND120, brain weights were decreased in the high dose group, liver to body weight ratios were increased for all three dose groups, with an increase in inflammatory cell foci in the epididymis in the high dose group. These data show that TCDD is a potent developmental toxin after exposure of the developing fetus, but that acute developmental exposure to TCDD on GD15 caused no decrease in sperm counts.

Manufacturing conditioned roughness and wear of biomedical oxide ceramics for all-ceramic knee implants

Background: Ceramic materials are used in a growing proportion of hip joint prostheses due to their wear resistance and biocompatibility properties. However, ceramics have not been applied successfully in total knee joint endoprostheses to date. One reason for this is that with strict surface quality requirements, there are significant challenges with regard to machining. High-toughness bioceramics can only be machined by grinding and polishing processes. The aim of this study was to develop an automated process chain for the manufacturing of an all-ceramic knee implant. Methods: A five-axis machining process was developed for all-ceramic implant components. These components were used in an investigation of the influence of surface conformity on wear behavior under simplified knee joint motion. Results: The implant components showed considerably reduced wear compared to conventional material combinations. Contact area resulting from a variety of component surface shapes, with a variety of levels of surface conformity, greatly influenced wear rate. Conclusions: It is possible to realize an all-ceramic knee endoprosthesis device, with a precise and affordable manufacturing process. The shape accuracy of the component surfaces, as specified by the design and achieved during the manufacturing process, has a substantial influence on the wear behavior of the prosthesis. This result, if corroborated by results with a greater sample size, is likely to influence the design parameters of such devices.

An investigation into the properties of non-digestible carbohydrates that selectively promote colonic propionate production

Short chain fatty acids (SCFA), including propionate, are produced by the bacterial fermentation of carbohydrates in the colon. Propionate has many potential roles in health, including inhibiting cholesterol synthesis, de novo lipogenesis and increasing satiety. The profile of SCFA produced is determined by both the substrate available and the bacteria present and may be influenced by environmental conditions within the lumen of the colon. Whilst it may be beneficial to increase colonic propionate production, dietary strategies to achieve this are unproven. Adding propionate to food leads to poorer organoleptic properties, and oral propionate is absorbed in the small intestine. The optimum way to selectively increase colonic propionate would be to select fermentable carbohydrates that selectively promote propionate production. To date, few studies have undertaken a systematic assessment of the factors leading to increased colonic propionate production making the selection of propiogenic carbohydrates challenging. The aim of this thesis was to identify the best carbohydrates for selectively increasing propionate production, and to explore the factors which control propionate production. This work started with a systematic review of the literature for evidence of candidate carbohydrates, which led to a screen of ‘propiogenic’ substrates using in vitro batch fermentations and mechanistic analysis of the impact of pH, bond linkage and orientation using a range of sugars, polysaccharides and fibre sources. A new unit for SCFA production was developed to allow comparison of results from in vitro studies encompassing a range different methodologies found in the literature. The systematic review found that rhamnose yielded the highest rate and proportion of propionate production whereas, for polysaccharides, β-glucan ranked highest for rate and guar gum ranked highest for molar production, but this was not replicated across all studies. Thus, no single NDC was established as highly propiogenic. Some substrates appeared more propiogenic than others and when these were screened in vitro. Laminarin, and other β-glucans ranked highest for propionate production. Legume fibre and mycoprotein fibre were also propiogenic. A full complement of glucose disaccharides were tested to examine the role glycosidic bond orientation and position on propionate production. Of the glucose disaccharides tested, β(1-4) bonding was associated with increased proportion of propionate and α(1-1) and β(1-4) increased the rate and proportion of butyrate production. In conclusion, it appears that for fibre to affect satiety, high intakes of fibre are needed, and which a major mechanism is thought to occur via propionate. Within this thesis it was identified that rather than selecting specific fibres, increasing overall intakes of highly fermentable carbohydrates is as effective at increasing propionate production. Selecting carbohydrates with beta-bonding, particularly laminarin and other β(1-4) fermentable carbohydrates leads to marginal increases in propionate production. Compared with targeted delivery of propionate to the colon, fermentable carbohydrates examined in this thesis have lesser and variable effects on propionate production. A more complete understanding of the impact of bond configurations in polysaccharides, rather than disaccharides, may help selection or design of dietary carbohydrates which selectively promote colonic propionate production substrates for inclusion in functional foods. Overall this study has concluded that few substrates are selectively propiogenic and the evidence suggests that similar changes in propionate production may be achieved by modest changes in dietary fibre intake

Architectural-Physical Co-Design of 3D CPUs with Micro-Fluidic Cooling

The performance, energy efficiency and cost improvements due to traditional technology scaling have begun to slow down and present diminishing returns. Underlying reasons for this trend include fundamental physical limits of transistor scaling, the growing significance of quantum effects as transistors shrink, and a growing mismatch between transistors and interconnects regarding size, speed and power. Continued Moore's Law scaling will not come from technology scaling alone, and must involve improvements to design tools and development of new disruptive technologies such as 3D integration. 3D integration presents potential improvements to interconnect power and delay by translating the routing problem into a third dimension, and facilitates transistor density scaling independent of technology node. Furthermore, 3D IC technology opens up a new architectural design space of heterogeneously-integrated high-bandwidth CPUs. Vertical integration promises to provide the CPU architectures of the future by integrating high performance processors with on-chip high-bandwidth memory systems and highly connected network-on-chip structures. Such techniques can overcome the well-known CPU performance bottlenecks referred to as memory and communication wall. However the promising improvements to performance and energy efficiency offered by 3D CPUs does not come without cost, both in the financial investments to develop the technology, and the increased complexity of design. Two main limitations to 3D IC technology have been heat removal and TSV reliability. Transistor stacking creates increases in power density, current density and thermal resistance in air cooled packages. Furthermore the technology introduces vertical through silicon vias (TSVs) that create new points of failure in the chip and require development of new BEOL technologies. Although these issues can be controlled to some extent using thermal-reliability aware physical and architectural 3D design techniques, high performance embedded cooling schemes, such as micro-fluidic (MF) cooling, are fundamentally necessary to unlock the true potential of 3D ICs. A new paradigm is being put forth which integrates the computational, electrical, physical, thermal and reliability views of a system. The unification of these diverse aspects of integrated circuits is called Co-Design. Independent design and optimization of each aspect leads to sub-optimal designs due to a lack of understanding of cross-domain interactions and their impacts on the feasibility region of the architectural design space. Co-Design enables optimization across layers with a multi-domain view and thus unlocks new high-performance and energy efficient configurations. Although the co-design paradigm is becoming increasingly necessary in all fields of IC design, it is even more critical in 3D ICs where, as we show, the inter-layer coupling and higher degree of connectivity between components exacerbates the interdependence between architectural parameters, physical design parameters and the multitude of metrics of interest to the designer (i.e. power, performance, temperature and reliability). In this dissertation we present a framework for multi-domain co-simulation and co-optimization of 3D CPU architectures with both air and MF cooling solutions. Finally we propose an approach for design space exploration and modeling within the new Co-Design paradigm, and discuss the possible avenues for improvement of this work in the future.

Domestic Rhodnius ecuadoriensis (Hemiptera, Reduviidae) infestation in Northern Peru: a comparative trial of detection methods during a six-month follow-up

Two passive methods in the assessment of intradomiciliary infestation by Rhodnius ecuadoriensis were tested: (i) the Gomes Nuñez sensor box (GN), (ii) sheets of white typing paper and (iii) one active timed manual method. The study was carried out in the Alto Chicama River Valley, Province of Gran Chimú, Department of La Libertad. The study design consisted of an initial searching of triatomines inside of the domestic environment by the manual capture active procedure (man/hour) covering all the studied houses. Then, matched pairs of GN boxes and paper sheets were simultaneously installed in the bedrooms of 207 households distributed in 19 localities. A comparative prospective trial of these passive detection devices were monitored at 2, 4 and, finally 6 months follow-up. Parasitological Trypanosoma rangeli and/or T. cruzi infections were investigated in two houses with high level of infestation by R. ecuadoriensis.16.9% of the 207 households investigated by an initial active manual method were infested with R. ecuadoriensis. The proportion of infested houses fluctuated from 6.2 to 55.5% amongst the 19 localities investigated. T. rangeli natural infection was detected in R.ecuadoriensis specimens collected in two households. Parasite rates in the bugs ranged from 16.6 to 21.7% respectively. The most striking fact was an average rate of salivary gland infection ranging from 7.4 to 8.3%. At the end of the sixth month period, a cumulative incidence of 31.4% of positive GN boxes against 15.9% for paper sheets was recorded. All three methods combined detected domestic infestation in 129 (62.3%) of the 207 houses studied in the 19 localities. The range of houses infested varies from 6.7% to 92.9%. In areas with low bug density infestation rates, the methodology experienced in our studies, seems to be the best choice for investigations on domestic R. ecuadoriensis populations.

Negotiation Support for Co-design of Business Services

Part 3: Product-Service Systems

Early consumption of liquids different to breast milk in Mexican infants under 1 year: results of the probabilistic National Health and Nutrition Survey 2012

Introduction: Studies on infant dietary intake do not generally focus on the types of liquids consumed. Objective: To document by age and breastfeeding status, the types of liquids present in the diet of Mexican children under 1 year of age (< 1 y) who participated in the National Health and Nutrition Survey 2012 (ENSANUT-2012). Methods: Analysis of the infant < 1 y feeding practices from the ENSANUT-2012 survey in non-breastfed (non-BF) and breastfed (BF) infants by status quo for the consumption of liquids grouped in: water, formula, fortified LICONSA milk, nutritive liquids (NL; thin cereal-based gruel with water or milk and coffee with milk) and non-nutritive liquids (non-NL) as sugared water, water-based drinks, tea, beans or chicken broth, aguamiel and coffee. In this infants < 1 y we analyzed the not grouped consumption of liquids in the first three days of life (newborns) from the mother's recall. Percentage and confidence intervals (95% CI) were calculated adjusting for survey design. Statistical differences were analyzed by Z test. Results: We observed a high consumption of human milk followed by formula (56.7%) and water (51.1%) in infants under 6 months of age (< 6 mo). The proportion of non-BF infants consuming non-NL was higher than for BF infants (p < 0.05). More than 60% of older infants (6 mo and < 1 y) consumed formula and were non-BF. In newborns formula consumption was predominant, followed by tea or infusion and water. Conclusions: Non-breast milk liquids are present undesirably in Mexican infants' diet and non-NL are consumed earlier than NL, revealing inadequate early dietary practices.

Population structure of pond-raised Macrobrachium amazonicum with different stocking and harvesting strategies

The effect of size-grading of juveniles prior to stocking, as well as selective harvesting, on the population structure of pond-raised Macrobrachium amazonicum was studied. A randomized-complete-blocks design with 4 treatments and 3 replicates was used. The treatments were: upper size-graded juveniles, lower size-graded juveniles, ungraded juveniles (traditional), and ungraded juveniles with selective harvesting. Twelve 0.01 ha earthen ponds were stocked at 40 juveniles m(-2), according to the relevant treatment. Every three weeks, random samples from each pond were obtained for biometry, and after 3.5 months, the ponds were drained and completely harvested. Animals were then counted, weighed, and sexed; males were sorted as Translucent Claw (TC), Cinnamon Claw (CC), Green Claw 1 (GC1), and Green Claw 2 (GC2), and females as Virgin (VF), Berried (BE), and Open (OF). The prawns developed rapidly in the ponds. attaining maturity and differentiating into male morphotypes after about 2 months in all treatments. The fast-growing juveniles (upper grading fraction) mostly did not constitute the dominant males (CC] and GC2) in the adult population. Population development was slower in ponds stocked with Lower prawns, whereas selective harvesting increased the frequency of GC1 and reduced the final mean weight of GC2 males. The proportion of males increased throughout the culture period, but was generally not affected by the stocking or harvesting strategies. Grading juveniles and selective harvesting slightly altered the population dynamics and structure, although the general population development showed similar patterns in ponds stocked with upper, lower, and ungraded juveniles, or selectively harvested. (C) 2010 Elsevier B.V. All rights reserved.